Influence of Configuration at the 4- and 6-Positions on the Conformation and Anomeric Reactivity and Selectivity of 7-Deoxyheptopyranosyl Donors: Discovery of a Highly Equatorially-Selective L-glycero-D-gluco-Heptopyranosyl Donor

Abstract

The preparation of four per-O-benzyl-d- or l-glycero-d-galacto and d- or l-glycero-d-gluco heptopyranosyl sulfoxides, and the influence of their side chain conformations on reactivity and stereoselectivity in glycosylation reactions are described. The side chain conformation in these donors is determined by the relative configuration of its point of attachment to the pyranoside ring and the two flanking centers in agreement with a recent model. In the d- and l-glycero-d-galacto glycosyl donors the d-glycero-d-galacto isomer with the more electron-withdrawing trans,gauche conformation of its side chain was the more equatorially-selective isomer. In the d- and l-glycero-d-gluco glycosyl donors, the l-glycero-d-gluco isomer with the least disarming gauche,gauche side chain conformation was the most equatorially selective donor. Variable temperature NMR studies, while supporting the formation of intermediate glycosyl triflates at −80 °C in all cases, were inconclusive owing to a change in decomposition mechanism with the change in configuration. It is suggested that the equatorial selectivity of the l-glycero-d-gluco isomer arises from H-bonding between the glycosyl acceptor and O6 of the donor which is poised to deliver the acceptor antiperiplanar to the glycosyl triflate resulting in a high degree of S_N2 character in the displacement reaction.

Graphical Abstract

Introduction

Oligosaccharides are important structural motifs in many biological systems and are involved in a vast array of biological processes,¹ and consequently the construction of glycosidic bonds in an efficient and stereocontrolled manner is of great interest and importance to glycobiology.² Most glycosylation reactions, however, occur at the boundary between of S_N1 and S_N2 processes which makes stereoselective glycosylation an complex and sometimes unpredictable task, necessitating further study of the numerous factors affecting selectivity.³

In recent years it has become increasingly apparent that the conformation of the side chain of glycosyl donors contributes significantly to their reactivity and selectivity, with the initial ground rules determined using conformationally locked bicyclic donors.^4–6 More recently, we have demonstrated by study of a series of sialic acid and Kdo donors isomeric at the 5- and/or 7-positions that side chain conformation also contributes to reactivity and selectivity in monocyclic donors (Figure 1).^7–10 Finally, recent studies have highlighted the role of side chain conformation in glycan recognition, and as a contributing factor to catalysis by the glycosyl hydrolases, glycosyltransferases, transglycosidases and glycoside phosphorylases during enzymatic cleavage and formation of glycosidic bonds.¹¹

Figure 1.

Predominant side chain conformation of glycosyl donors in the neuraminic acid and ulosonic series and their relative configurations from C5–C7, as depicted on Fischer projection formulas of the parent sugar.

We define the three staggered conformations of the exocyclic bond to the side chain (hereinafter the side chain conformation) as being either gauche,gauche (gg), gauche,trans (gt) or trans,gauche (tg) (Figures 1 and 2), where the first and second terms refer to the position of the C6–O6 bond relative to C5–O5, and C5–C4 bonds, respectively.^12–14 As first determined by Marchessault and Perez on the basis of analysis of crystal structure databases,¹⁵ and subsequently by many groups using NMR spectroscopy, conformationally mobile glucopyranosides can typically be considered as an ~ 50:50 equilibrating mixture of gg and gt conformers, while the isomeric galactopyranosides are populate an ~ 15:55:30 gg:gt:tg mixture (Figure 2).^12–14,16

Figure 2.

Staggered conformation of the hexopyranose side chain illustrated for d-Glucose and D-Galactose and their relative populations in free solution.

Our studies with the 5- and/or 7-epi-sialic acid and Kdo series (Figure 1) revealed the conformational space available to the side chains of higher carbon sugars (here defined as those with a longer side chain than the hydroxymethyl group of typical hexopyranosides) is significantly restricted by the presence of the extra C–C bond that extends the side chain and that the predominant conformation of these higher carbon sugar side chains is controlled by the relative configurations of the stereogenic center at the point of attachment of the side chain to the pyranose ring and by the two flanking centers, ie, by a simple stereotriad comprising C5, C6, and C7 in the sialic acids.¹⁷ On this basis, and comparison with the solution and crystal phase conformations of the four pentitol sugars we devised a simple model whereby the arabino configuration of the three centers in question leads to the predominant tg conformation of the side chain, while the lyxo configuration results in the predominant population of the gg conformation. The ribo and xylo configurations on the other hand result in the predominant population of the two gt conformations (Figure 1).¹⁷

In spite of the patterns evident in our studies on the influence of configuration and conformation of sialic acid side chains on reactivity and selectivity at the anomeric center comparisons were marred to some extent by the different protecting groups employed, which in turn was a function of the complex synthesis required to access the donors in some series. Seeking to generalize the models and standardize them to other higher carbon sugars we set out to construct and analyze a series of four 7-deoxyheptopyranosyl donors differing in configurations at the 4- and 6-positions, i.e, comprising the arabino, lyxo, ribo and xylo configurations of the three contiguous stereogenic centers thought to control side chain conformation, and all carrying the same suite of protecting groups. We report here on the synthesis and conformational analysis of this series of four such donors (Figure 3) and confirm the predictions of side chain conformation from our model. Based on a comparative study of the same four donors with a standard series of acceptor alcohols, we determine that the d-glycero-d-galacto and l-glycero-d-galacto donors conform to expectation with the former isomer having the tg conformation of its side chain being more equatorially selective than the latter with its gt side chain conformation. Unexpectedly, however, the model fails with regard to selectivity in the d- and l-glycero-d-gluco series where the l-glycero-d-gluco configured donors exhibits unanticipatedly high equatorial selectivity despite the gg conformation of its side chain. This unexpected and novel selectivity, which reveals the pitfalls in extrapolation from one series (Figure 1) of donors to another (Figure 3), appears to arise from donor-acceptor hydrogen bonding involving the benzyl ether at the 6-position of the l-glycero-d-gluco configured donor and potentially opens the way for the design of further series of selective glycosyl donors.

Figure 3.

D- and L-glycero-D-gluco- and D- and L-glycero-D-galacto heptopyranoses and the predicted conformations of their exocyclic bonds.

Result and discussion

Donor synthesis:

Intermediate 6 was obtained from penta-O-acetyl-β-d-galactopyranose by the literature protocol.¹⁸ Dess-Martin periodinane oxidation to give the corresponding aldehyde followed by treatment with MeMgBr at −78 °C gave a complex reaction mixture from which only 16% of the desired product could be isolated. In contrast, reaction with the less basic methylcerium reagent, derived by reaction of MeMgBr with cerium chloride,¹⁹ afforded the required C-6-methyl-substituted compound, 7 in 71% yield and as a 11:1 mixture of diastereomers. After protection of the so-formed alcohol as the benzyl ether 8 in 89% yield, oxidation with mCPBA afforded the corresponding sulfoxide (9) as a mixture of two stereoisomers in 81% yield. The donor 12, epimeric with 9 at the 6-postion, was obtained from 7 by Dess-Martin oxidation followed by sodium borohydride reduction giving 10 in 90% yield as a 1:22 mixture of isomers. Subsequent benzylation and mCPBA oxidation then afforded the sulfoxide 12 in 79% yield as a mixture of isomers (Scheme 1).

Scheme 1.

Synthesis of 7-deoxy-d-glycero-d-galactoheptopyranose and 7-deoxy-l-glycero-d-galactoheptopyranose donors 9 and 12

The d-glycero-d-gluco and l-glycero-d-gluco configured donors were obtained analogously from 13, which was obtained by the literature protocol.²⁰ Thus, oxidation of 13 employing the Dess-Martin periodinane followed by immediate treatment with methyl magnesium chloride in THF furnished the C6-methyl substituted products 14 and 15, in a 3:1 ratio. Protection of the remaining hydroxyl group as the benzyl ether resulted in the thiogycosides 16 and 18, which were subjected to standard mCPBA oxidation conditions to afford sulfoxides 17 and 19 in good yield (Scheme 2).

Scheme 2.

Synthesis of 7-deoxy-l-glycero-d-glucoheptopyranose (17) and 7-deoxy-d-glycero-d-glucoheptopyranose (19) donors

The configuration at C6 of the donors 9, 12, 17 and 19 was assigned as described in the Supporting Information by conversion to a set of rigid bicyclic congeners carrying the 4,6-O-benzylidene protecting group (Schemes S1 and S2) and analysis of their NOE and ROE spectra, and ³J_H5,H6 coupling constants, in the usual manner (Figures S1 and S2). The reversal of stereoselectivity observed in the Grignard additions in going from the galactose to the glucose series (Schemes 1 and 2) is consistent with literature observations and the changes from a chelation model involving O4 in the galactose series to one invoking the ring oxygen in the glucose series.^21,22

Side Chain Conformation:

Side chain conformations were determined at the level of the 6-hydroxy thioglycosides before final benzylation and conversion to the ultimate sulfoxides, because of the less complex nature of the NMR spectra, by a combination of coupling constant analysis and NOE measurements (Figure 4). Thus, the d-glycero-d-galacto system 7 displayed ³J_H5,H6 of 8.0 Hz and an NOE interaction between H₅ and the terminal methyl group consistent with the very predominant population of the tg conformation. The l-glycero-d-galacto thioglycoside 10 on the other hand had ³J_H5,H6 of 7.5 Hz and an NOE interaction between H₄ and the methyl group, indicative of a dominant gt conformation. In the d-gluco series, the d-glycero isomer 15 had an NOE interaction between the methyl group and H₄ and ³J_H5,H6 of 3.9 Hz consistent with the gt conformation, while the l-glycero isomer 14 had an NOE interaction between the methyl group and H₅ and ³J_H5,H6 of 1.6 Hz indicative of the gg conformation. While the magnitudes of ³J_H5,H6 in 7 and 10 at first sight appear small for a pair of antiperiplanar vicinal hydrogens on the side chain of a hexopyranoside, after correction for the presence of the additional C–C bond, they are consistent with literature vales derived from rigid bicyclic systems.^23,24 Similarly, the discrepancy between the two ³J_H5,H6 couplings constant between pairs of gauche protons spanning a hexopyranoside side chain is consistent with the presence and location of the addition C–C bond as determined with rigid bicyclic models.²³ No significant differences in the ³J_H5,H6 coupling constants of the subsequent members of each series were observed indicating that neither benzylation of O6, nor conversion of the thioglycosides to the corresponding sulfoxides resulted in an appreciable change in side chain conformation.

Figure 4.

Assigned Side Chain Conformations with Diagnostic Data

The assignment of a predominant tg conformation to the side chain of the d-glycero-d-galacto donor 7 is consistent with the tg side chain conformation of the pseudoenantiomeric sialic acid donors 4 and 5, while the predominant gt conformation assigned to the side chain of its l-glycero-d-galacto isomer 10 is consistent with that of the pseudoenantiomeric sialic acid donor 2. Similarly, the assignments of the gg conformation to the side chain of the l-glycero-d-gluco isomer 14 and of the gt conformation to the side chain of the d-glycero-d-gluco donor 15 are consistent with those of the pseudoenantiomeric sialic acids 1 and 3, respectively, i.e., the predictions of side chain conformations based on the analysis of the relative configurations of the C4–C6 stereotriad presented in Figure 3 are fully borne out. It follows that the differing side chain conformations in the sialic acids 1–5 are predominantly determined by the relative configurations of the C5–C7 stereotriads and not by the differences in alcohol protecting (acetyl versus benzoyl) nor by the differences in electronegative group at the 5 and 7-positions (esters, amides, and azides).

Glycosylation

Glycosylation reactions were carried out by activating sulfoxides 9, 12, 17 and 19 with triflic anhydride in the presence of the hindered non-nucleophilic base TTBP at −78 °C in 0.20 M CH₂Cl₂ followed by the addition of 1.1 equivs acceptor alcohols in the form of 0.5 M solutions in dichloromethane, giving rise to the coupled products in good yield as presented in Tables 1 and 2.²⁵

Table 1.

Glycosylation reactions with D-glycero-D-galacto donor 9^a and L-glycero-D-galacto donor 12^a

Entry	Acceptor	Donor	Product	Yield (%)b	ax:eqc	Donor	Product	Yield (%)b	ax:eqc
1.		9		64	1:6.0	12		53	1:1.6
2.		9		73	1:16.7	12		58	1:5.9
3.		9		79	1:14.2	12		70	1:4.1
4.		9		70	1:4.0	12		54	1:1.1
5.		9		62	1:3.2	12		60	1:1.7
6.		9		77	1:5.1	12		69	1:1.8
7.		9		55	1:2.1	12		59	3.9:1
8.		9		68	2.9:1	12		61	10.2:1

^aAll reactions were carried out at −78 °C with activation by Tf₂O/TTBP. The donor to acceptor ratio is 1.0:1.1.

^bIsolated yield.

^cAnomeric ratios were determined by integration of the ¹H NMR spectra of the crude reaction mixtures.

Table 2.

Glycosylation reactions with L-glycero-D-gluco donor 17^a D-glycero-D-gluco donor 19^a

Entry	Acceptor	Donor	Product	Yield (%)b	ax:eqc	Donor	Product	Yield (%)b	ax:eqc
1.		17		57	eq only	19		61	1:1.2
2.		17		56	eq only	19		52	1:1.1
3.		17		49	1:23.6	19		60	1:1.1
4.		17		63	1:7.9	-	-	-	-
5.		17		59	1:7.7	-	-	-	-
6.		17		63	1:1.7

^aAll reactions were carried out at −78 °C with activation by Tf₂O/TTBP. The donor to acceptor ratio is 1.0:1.1.

^bIsolated yield.

^cAnomeric ratios were determined by integration of the ¹H NMR spectra of the crude reaction mixtures

The anomeric configuration of the various glycosides obtained was assigned based on the ³J_1,2 coupling constant in the usual manner, with that for the equatorial isomers found in the range of 7.6–7.8 Hz, as compared to the 3.7–3.9 Hz of the axial anomers.

In the galactose-derived series the d-glycero-d-galacto-configured donor 9 with its predominant tg side chain conformation showed excellent selectivity for the formation of the equatorial glycoside with simple primary, secondary and tertiary alcohols (Table 1, entries 1–3), modest equatorial selectivity with primary carbohydrate acceptors (Table 1, entries 4 and 5), modest to poor equatorial selectivity with two secondary carbohydrate acceptors (Table 1, entries 6 and 7), and finally modest axial selectivity with diacetone-d-glucose as acceptor (Table 1, entry 8). With epimeric l-glycero-d-galacto-configured donor 12, with the predominant gt side chain conformation, the analogous trend in selectivities was seen with the same series of acceptors, however, the overall equatorial selectivity was generally lower than seen with 9, and the switch over from equatorial to axial selectivity began with the glucopyranose 4-OH acceptor (Table 1, entry 7) and was much more pronounced with the glucofuranose 3-OH acceptor (Table 1, entry 8). This pattern is consistent with equatorial selectivity being promoted to a greater extent in a donor with the tg conformation of the side chain than with the more arming gt conformation and matches that seen in the sialic acid series. The fall-off in equatorial selectivity with decreased nucleophilicity of the acceptor alcohols is consistent with the patterns observed by Codée and others in the hexopyranoside series of donors.²⁶

Turning to the glucose-derived series, we were surprised to discover that the l-glycero-d-gluco configured donor 17, with the predominant gg conformation of its side chain was highly equatorially selective in its couplings with simple alcohols and with a primary carbohydrate acceptor (Table 2, entries 1–3). Significant equatorial selectivity was maintained with two secondary carbohydrate acceptors (Table 2, entries 4 and 5), whereas poor equatorial selectivity was observed with the glucofuranose 3-OH acceptor (Table 2, entry 6). On the other hand, the d-glycero-d-gluco donor 19, with the predominant gt conformation of its side chain, showed little to no selectivity with the two simple alcohols and a primary carbohydrate-based acceptor (Table 2, entries 1–3) and accordingly was not pursued further.

Overall, the relationships between relative configuration, side chain conformation, and anomeric selectivity in the series of isomeric donors 9, 12, 17 and 19 studied here are consistent with the patterns established previously in the sialic acid series (Figure 1), with the one major exception of the highly equatorially selective 17. Thus, the excocyclic bonds of the d-glycero-d-galacto donor 9 and the pseudaminic acid and Kdo donors 4 and 5 all have the arabino configuration of the branch point and its two flanking centers, the tg conformation of the side chain and, with the exception of 17, the highest equatorial selectivity. The l-glycero-d-galacto donor 12 has the xylo configuration of the same three stereogenic centers as does the 5-epi-neuraminic acid donor 2, similarly adopts the gt conformation of the side chain, and has somewhat reduced anomeric selectivity. The d-glycero-d-gluco configured donor 19, like the 7-epi-neuraminic acid donor 3 has the ribo configuration of the three stereogenic centers that control side chain conformation, and also shares the gt conformation of the side chain and modest anomeric selectivity in its glycosylation reactions. The exception to the overall trend of configuration, conformation, and selectivity seen with the sialic acids and the simplified models studied here is the l-glycero-d-gluco configured donor 17: like the neuraminic acid donor 1 it has the lyxo configuration of the three key stereogenic centers, and the anticipated gg conformation of its side chain but, contrary to our initial expectations based on the selectivity observed with 1 and analogous systems, it displays the highest equatorial selectivity among the isomeric donors studied here.

Low temperature NMR studies

In an attempt to understand the unexpected selectivity of donor 17, we turned to the use of variable temperature NMR spectroscopy to probe the nature of the activated donors and their relative stabilities.²⁷ Accordingly, the four donors 9, 12, 17, and 19 were activated at −80 °C in deuteriodichloromethane solution in the presence of TTBP by the addition of Tf₂O, and ¹H, and ¹³C NMR spectra were recorded at −80 °C. The temperature of the NMR probe was then raised in 10 °C increments, with ¹H NMR spectra recorded at each step, until −10 °C (Supporting Information, Pages S153, S161, S171, S179). Finally, decomposition products were isolated and characterized in each case.

Starting with the d-glycero-d-galacto donor 9, conversion into corresponding glycosyl triflate (53) began at −80 °C, but was not complete until −50 °C when a clean ¹H NMR spectrum was observed (Figure 5). The anomeric proton of this glycosyl triflate appears at δ 6.19 as a doublet (³J_1,2 = 3.82 Hz), whereas the corresponding carbon resonated at δ107.7. A peak was observed at δ −76.19 in the ¹⁹F NMR spectrum (SI). These ¹H, ¹³C and ¹⁹F chemical shifts are fully consistent with the very predominant formation of a covalent axial glycosyl triflate.²⁷ Warming the NMR probe by 10 °C increments resulted in decomposition of the glycosyl triflate intermediate between −20 and −10 °C, at which point analysis of the reaction mixture by electrospray mass spectrometry revealed the presence of one predominant product with m/z = 559 [M+Na⁺], which we attribute to the glycal (54). Unfortunately, all attempts to isolate 54 failed, but afforded instead the 1,1’-disaccharides 56 and 57 in 43% yield as a mixture of two isomers (α:β, 1:1.5), which nevertheless supports the formation of glycal 54 as the immediate decomposition product from 9.

Figure 5:

¹H NMR spectra of donor 9 (a) at −80 °C prior to addition of Tf₂O; the anomeric proton appears at δ3.80; (b) after addition of Tf₂O and warming to at −50 °C; the anomeric proton of the glycosyl triflate appears at 6.19 as a doublet (³J_1,2 = 3.82 Hz).

In the case of the l-glycero-d-galacto donor 12, a different pattern of reactivity was observed (Figure 6). A glycosyl triflate (58) was clearly formed at −80 °C, characterized by ¹H, ¹³C and ¹⁹F chemical shifts of δ 6.26 (d, ³J_1,2 = 3.41 Hz), 109.0 and −76.21 for the anomeric proton, carbon, and triflate resonances respectively, but decomposition was almost complete by −70 °C when only traces of the glycosyl triflate remained and the 1,6-anhydro derivative 59 was observed as the major product. Subsequent isolation afforded 59 in 53% yield.

Figure 6:

¹H NMR spectra of donor 12 (a) at −80 °C prior to addition of Tf₂O; the anomeric proton appears at δ 4.43 ppm; (b) after addition of Tf₂O and warming to −70 °C, the anomeric proton of the residual triflate appears at δ 6.26 ppm as a doublet (³J_1,2 = 3.41 Hz).

Analogous study of the NMR study of the l-glycero-d-gluco donor 17 showed the clean formation of an axial glycosyl triflate (60) by −60 °C, with characteristic resonances at δ 6.15 (d, ³J_1,2 = 3.14 Hz), δ 107.5, and δ −76.18 in the ¹H, ¹³C and ¹⁹F NMR spectra (figure. 7b). On gradual warming this glycosyl triflate decomposed around −40 °C with formation of the 1,6-anhydro sugar 61, which was isolated in 43% yield.

Figure 7:

¹H NMR spectra of donor 17 (a) at −80 °C prior to addition of Tf₂O; the anomeric proton appears at δ 3.91; (b) after addition of Tf₂O and warming to −60 °C; the anomeric proton of the glycosyl triflate appears at δ 6.15 (d, ³J_1,2 = 3.14 Hz).

Finally, the d-glycero-d-gluco donor 19 was observed to cleanly form a glycosyl triflate (62) by −60 °C as indicated by the anomeric proton that resonated at δ 6.16 (d, ³J_1,2 = 3.08 Hz) the anomeric carbon at δ 107.1 and the glycosyl triflate CF₃ resonance at δ −75.27 in the ¹H, ¹³C, and ¹⁹F NMR spectra, respectively (Figure 8b). On warming, decomposition of this triflate began around −40 °C and was complete by −30 °C and afforded primarily the 1,6-anhydro sugar 63 (Figure 9) which could be isolated in 29% yield.

Figure 8:

¹H NMR spectra of donor 19 (a) at −80 °C prior to addition of Tf₂O; the anomeric proton appears at δ 3.91; (b) after addition of Tf₂O and warming to −60 °C the anomeric proton of the glycosyl triflate appears at δ 6.16(d, ³J_1,2 = 3.08 Hz).

Figure 9.

Structures of intermediates and decomposition products obtained during low temperature NMR studies.

Overall, all four donors afforded an axial glycosyl triflate on activation with triflic anhydride but the decomposition temperatures of these triflates varied considerably. Three of the four glycosyl triflates decomposed preferentially to give 1,6-anhydro sugars, whereas the fourth underwent apparent elimination to give a glycal, which in turn underwent partial hydration and coupling on attempted isolation. The formation of 1,6-anhydro sugars, side products in many glycosylation reactions,²⁸ is best explained by intramolecular attack of the side chain benzyl ether on the glycosyl triflate through an exploded transition state with significant oxocarbenium ion character and a ³H₄ or ^2,5B conformation of the pyranose ring (Scheme 3). The formulation of these ring closure reactions as S_N2-like reactions with exploded transition states is consistent with current thinking on O-glycosylation reactions,^3d,29 and avoids the need to write a disfavored 5-endo-trig ring closure as would be required by a pure S_N1 mechanism. It is apparent that the failure of the d-glycero-d-galacto configured triflate 53 to undergo ring closure to the endo-substituted 1,6-anhydro derivative 55 is the result of an unfavorable steric interaction by the terminal methyl group and the pseudoequatorial benzyloxy group at the 4-position in either of the proposed transition states for ring closure. The evidently more facile closure of the l-glycero-d-galacto triflate to the corresponding 1,6-anhydrogalactose derivative 59 also appears to be the result of steric interactions between the terminal methyl group and or the benzyloxy group at the 6-position and the pseudoequatorial benzyloxy group at the 4-position, which in this case favorably orient the side for ring closure in both the ^2,5B and ⁴H₃ conformers. Any favorable or unfavorable steric interactions between the side chain and the benzyloxy group at the 4-position are alleviated in the d- and l-glycero-d-gluco triflates leading to the formation of the 6-endo methyl-1,6-anhydroglucose derivative because of the pseudoaxial nature of the substituent at the 4-position. 1,6-Anhydroglucose derivatives substituted at the 6-endo-position have been described previously,³⁰ albeit prepared by a different method involving substitution on a pre-existing bicyclic framework.

Scheme 3.

Mechanism of 1,6-anhydro product formation

The fact that the significant difference in stabilities of the d- and l-glycero-d-galacto triflates can be attributed to steric interactions in the transition states for ring closure to the corresponding 1,6-anhydro derivatives prevents us from drawing any firm conclusions correlating the stability of the two diastereomeric triflates and its influence on selectivity in their respective glycosylation reactions. Similarly, little of any use regarding the influence of side chain on intermolecular reactivity and glycosylation selectivity can be gleaned from the comparable decomposition temperatures of the two d- and l-glycero-d-gluco triflates as obviously the transition states for ring closure do not resemble those for O-glycosylation.

Ultimately, the most interesting and unexpected observation in this study is the highly selective formation of equatorial glycosides with the l-glycero-d-gluco configured donor 17 with the preferred gg conformation of the side chain which, according to the earlier bicyclic models,^5,6 should have been the most reactive and least equatorially selective of the compounds studied. We suggest that this observation is best explained by donor-acceptor hydrogen bonding involving the benzyloxy group in the side chain of the donor in its gg conformation serving as H-bond acceptor and directing group. Thus, as the C1 to OTf bond lengthens and oxocarbenium character develops the ⁴C₁ chair conformer will undergo distortion toward a ⁴E envelope 64 and/or the closely related ⁴H₃ half-chair conformation 65 in either of which O6 is ideally placed to accept a hydrogen bond from the acceptor and stabilize a loose S_N2-like transition state (Scheme 4). This hypothesis is consistent with Whitfield and Guo’s DFT computations, including proton transfer from the acceptor to O6 at the transition state, on the reaction of methanol with a tetra-O-methyl-α-d-glucopyranosyl donor, and with Liu’s recent molecular dynamics study on glycosylation mechanisms.³¹ The main difference between the models proposed by Whitfield and Liu and their respective coworkers on with prototypical tetra-O-alkyl-α-d-glucopyranosyl donors and that proposed here for the l-glycero-β-d-glucopyranosyl triflate 60 is the preorganization of the side chain in the latter into the gg conformation ideal for the key donor-acceptor hydrogen bond, which reduces the entropy of activation and so increases selectivity with respect to other transition states giving rise to the opposite anomer of the product. Donor acceptor hydrogen bond-mediated aglycone delivery in general is a much-discussed concept in recent years, albeit the focus is typically on the use of basic protecting groups in the donor as hydrogen bond acceptor.³²

Scheme 4.

Mechanistic hypothesis for the equatorial selectivity of L-glycero-D-gluco donor 17

To test the hypothesis that donor-acceptor hydrogen bonding factors into the equatorial selectivity observed with donor 17, we prepared the corresponding 6-O-acetyl thioglycoside 66 by acetylation of 14 under standard conditions in 90% yield and converted it to the sulfoxide 67 by mCPBA oxidation in 83% yield. The ³J_5,6 coupling constant of 1.78 Hz in the 6-O-acetyl glycosyl donor 66, and those of = 1.71 and 1.92 Hz for two isomers of sulfoxide 67, are consistent with that of 1.60 Hz seen in the analogous 6-O-benzyl donor 16 indicating that the nature of the protecting group at the 6-position has no significant influence of side chain conformation in the l-glycero-d-gluco series and that 66 and 67 retain the gg conformation. Coupling of 67 to 1-adamantanol under the standard conditions gave 61% of a 1.94:1 axial to equatorial mixture of glycosides 68 (Scheme 5), which differs significantly from the exclusive formation of the equatorial glycoside observed on coupling of 17 to the same acceptor alcohol (Table 2, entry 2). Clearly, the nature of the protecting group, ether or ester, at the 6-position has a very significant influence on the stereochemical outcome of glycosylations in the l-glycero-d-gluco series, consistent with the more basic benzyl ether in 17 serving as a better hydrogen bond acceptor than the less basic acetate ester of 67. The alternative possibility of stereodirecting participation by the ester in 67 steering the glycosylation toward preferential axial glycoside formation is considered unlikely.^{3d, 33}

Scheme 5.

Unselective glycosylation with the 6-O-acetyl-L-glycero-D-gluco heptopyranosyl donor 67.

A final issue concerns the difference between the sialic acid series with which we began and the simple 7-deoxyheptopyranosyl series of donors studied here; namely that the l-glycero-d-gluco donor 17 is the most selective in the present series, whereas the neuraminic acid donor 1 is among the least selective in its series despite the fact that both have the same lyxo relative configuration at the point of attachment of the side chain to the pyranose ring and its two flanking centers and both have the gg conformation of the side chain. The two series are clearly not the same and differ most prominently by the presence of the carboxylate ester at the anomeric position and the absence of a C–O bond at the 2-position of the pyranose ring in the sialic acid series, but also by the nature of the protecting groups. If donor-acceptor hydrogen bonding is accepted as the underlying reason for the equatorial selectivity of 17 (Schemes 4 and 5), it is apparent that it cannot play as significant a role in the reactions of 1, which in turn is consistent with the less basic nature of the acetate protecting groups in 1 than the benzyl ethers in 2. Unfortunately, while research into the use of ethers as protecting groups in sialic acid donors has been initiated,³⁴ it has not yet been extended under comparable conditions to comparisons of reactivity and selectivity across a spectrum of diastereomeric donors such as those employed here.

Conclusion

Continuing our studies on the role of side chain conformational effects in anomeric reactivity and selectivity, we report the synthesis, conformational analysis, reactivity and selectivity of a series of four diastereomeric 6-C-methyl galacto and glucopyranosyl donors. Consistent with expectations based on earlier studies in the sialic series, the d-glycero-d-galacto and l-glycero-d-galacto isomers have the tg and gt conformations of the side chain while the d-glycero-d-gluco and l-glycero-d-gluco isomers have the gt and gg conformations: side chain conformations of higher carbon sugars can be reliably predicted based on a simple model coupled with inspection of Fischer projections formulas. Somewhat to our surprise, however, while the d-glycero-d-galacto configured donor exhibited significantly greater equatorial selectivity than the l-glycero-d-galacto isomer consistent with the model, the d-glycero-d-gluco isomer was more reactive than l-glycero-d-gluco isomer which generally exhibited the greatest equatorial selectivity of the whole series. This observation is rationalized in terms of stereodirecting donor-acceptor hydrogen bonding in the l-glycero-d-gluco isomer with O6 of the donor serving as H bond acceptor. Transition states involving ⁴E or ⁴H₃ conformations of the activated donor encompassing this type of donor-acceptor hydrogen are consistent with recent DFT and metadynamics studies of the reactions of simple per-O-methylated glucopyranosyl donors with simple alcohols and are especially favored in the present case by the gg side chain conformation very predominantly adopted in the ground state by the l-glycero-d-gluco donor which results in a decrease in entropy of activation and so of the activation energy for formation of the equatorial glycoside.

General experimental details.

All reactions were carried out under argon unless otherwise stated. Solvents used for column chromatography were analytical grade and were purchased from commercial suppliers. Thin-layer chromatography was carried out with 250 μm glass backed silica (XHL) plates. Detection of compounds was achieved by UV absorption (254 nm) and by staining with 10% sulfuric acid in ethanol. Purification of crude residues was performed by silica gel chromatography using 230–400 mesh grade 60 silica. Specific rotations were measured in chloroform on an automatic polarimeter with a path length of 10 cm. NMR spectra were recorded in C₆D₆ and CDCl₃ at either 500, 600 or 900 MHz as indicated. High-resolution (HRMS) mass spectra were recorded in the electrospray mode using an orbitrap mass analyzer (ThermoFisher ESI-Orbitrap). The chemical shifts (δ) are recorded in ppm and the multiplicities are abbreviated as follows: s (singlet), m (multiplet), br (broad), d (doublet), t (triplet) and q (quartet).

Preparation of acceptors.

Methyl 2,3,4-tri-O-benzyl-α-d-glucopyranoside (23).²⁰ This acceptor was prepared according to the literature method (1.40 g, 98%) as a colorless syrup. The data are consistent with the literature.

1,2:3,4-O-Di-isopropylidene-α-d-galactopyranoside (24).³⁵ The data are consistent with the literature.

Methyl 2,3-O-isopropylidene-α-L-rhamnoside (25).³⁶ The data are consistent with the literature.

Methyl 2,3,6-tri-O-benzyl-α-d-glucopyranoside (26).³⁷ This acceptor was prepared according to the literature method (4.51 g, 90%) as a colorless syrup. The data are consistent with the literature.

p-Methylphenyl 2,3,4-Tri-O-benzyl-1-thio-β-d-galactopyranoside (6).¹⁸ This compound was prepared according to the literature method (2.60 g, 91 %) as a white foam. The spectral data are consistent with the literature.

p-Methylphenyl 2,3,4-Tri-O-benzyl-7-deoxy-1-thio-d-glycero-α-d-galacto-heptopyranoside (7). To a solution of 6 (0.60 g, 1.08 mmol) in dry CH₂Cl₂ (5 mL) was added Dess Martin periodinane (0.51 g, 1.19 mmol). The mixture was stirred at room temperature for 3h until complete consumption of starting material as observed by TLC analysis. The reaction was diluted with 5 ml sat. NaHCO₃, 5 ml Na₂S₂O₃ solution, the layers were separated, and the aqueous layer was extracted three times with CH₂Cl₂ (3 × 10 ml). The combined organic layers were washed with brine, dried over Na₂SO₄, filtered, and concentrated under reduced pressure to afford crude residue which was used immediately without further purification.

THF (5 mL) was added at room temperature to vigorously stirred anhydrous CeCl₃ (0.31 g, 1.25 mmol, 2.0 equiv.) to form a uniform white suspension, which was stirred for 2 h. The resulting suspension was cooled to 0 °C and addition of methylmagnesium bromide (1.88 mL, 1.0 M in THF, 1.88 mmol, 3.0 equiv.) was done in a dropwise manner over 10 min to form an off-white suspension. The resulting suspension was stirred for 1h, whereupon glycosyl aldehyde (0.35 g, 0.63 mmol, 1.0 equiv.) in THF (3.0 mL) was added dropwise over 5 min. and the reaction mixture warmed gradually to room temperature. After 1h, the reaction mixture was cooled to 0 °C, quenched with sat. NH₄Cl (10 mL) and extracted with EtOAc (2 × 15 mL). The organic extracts were combined, washed with brine (15 mL), dried over Na₂SO₄, filtered, and evaporated under reduced pressure and the resulting residue was purified by flash column chromatography on silica gel (hexane:ethyl acetate; 4:1) to yield 7 and 10 stereoisomers in 11:1 ratio (combined yield: 0.44 g, 71% ) as a colorless syrup. 7: [α]_D²⁰ = −8.3 (c = 1.4, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.46 – 7.41 (m, 4H), 7.39 – 7.27 (m, 13H), 7.04 (d, J = 8.0 Hz, 2H), 5.01 (d, J = 11.7 Hz, 1H), 4.87 (d, J = 10.2 Hz, 1H), 4.78 (d, J = 12.0 Hz, 3H), 4.73 (d, J = 11.8 Hz, 1H), 4.56 (d, J = 9.7 Hz, 1H), 4.10 (d, J = 2.7 Hz, 1H), 3.91 (td, J = 9.5, 8.9, 4.4 Hz, 2H), 3.58 (dd, J = 9.2, 2.7 Hz, 1H), 2.94 (d, J = 8.0 Hz, 1H), 2.30 (s, 3H), 1.18 (d, J = 6.3 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 138.7, 138.4, 138.3, 137.4, 132.5, 130.4, 129.6, 128.66, 128.60, 128.5, 128.4, 128.0, 127.8, 127.7, 88.6, 84.6, 82.4, 77.9, 75.8, 74.0, 73.1, 71.8, 65.7, 21.2, 20.7. HRMS (ESI): m/z calcd for C₃₅H₃₈O₅SNa [M + Na] 593.2332 found 593.2307.

p-Methylphenyl 2,3,4,6-Tetra-O-benzyl-7-deoxy-1-thio-d-glycero-α-d-galacto-heptopyranoside (8). To a solution of 7 (0.50 g, 0.87 mmol) in dry DMF (3 mL) were added sodium hydride (49.10 mg, 1.22 mmol) and BnBr (130 μL, 1.05 mmol) at 0 °C. The reaction mixture was gradually warmed to room temperature and stirred till completion with monitoring by TLC (hexane:ethyl acetate 4:1, Rf = 0.8) and then quenched with methanol (0.5 mL). It was diluted with ethyl acetate and washed with water and brine, dried over anhydrous Na₂SO₄, filtered, and evaporated under reduced pressure. The residual syrup was purified by silica gel column chromatography (hexane:ethyl acetate 9:1) to afford 8 (0.51 g, 89%) as a colorless syrup. [α]_D²⁰ = −9.6 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.46 (d, J = 7.8 Hz, 2H), 7.40 (d, J = 7.7 Hz, 2H), 7.37 – 7.21 (m, 18H), 7.03 (d, J = 7.8 Hz, 2H), 5.03 (d, J = 11.4 Hz, 1H), 4.82 (d, J = 10.2 Hz, 1H), 4.76 – 4.71 (m, 3H), 4.59 – 4.54 (m, 2H), 4.52 (d, J = 11.4 Hz, 1H), 4.22 (d, J = 11.2 Hz, 1H), 4.19 (d, J = 2.6 Hz, 1H), 3.95 – 3.87 (m, 2H), 3.60 (dd, J = 9.3, 2.6 Hz, 1H), 3.15 (d, J = 8.7 Hz, 1H), 2.31 (s, 3H), 1.30 (d, J = 6.0 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.2, 138.5, 138.4, 137.3, 132.3, 130.4, 129.6, 128.5, 128.48, 128.42, 128.2, 127.89, 127.81, 127.78, 127.70, 127.6, 127.5, 127.3, 88.4, 84.7, 81.7, 77.6, 75.7, 74.4, 73.4, 72.86, 72.81, 70.7, 21.2, 16.7. HRMS (ESI): m/z calcd for C₄₂H₄₄O₅SNa [M + Na] 683.2801 found 683.2789.

p-Methylphenyl 2,3,4-Tri-O-benzyl-7-deoxy-1-thio-l-glycero-α-d-galacto-heptopyranoside (10). To a solution of 7 (0.20 g, 0.36 mmol) in dry CH₂Cl₂ (2 mL) was added Dess Martin periodinane (0.30 g, 0.72 mmol). The mixture was stirred at room temperature for 3h until complete consumption of starting material as observed by TLC analysis. The reaction was diluted with 2 ml sat. NaHCO₃, 2 ml Na₂S₂O₃ solution, the layers were separated, and the aqueous layer was extracted three times with CH₂Cl₂ (3 × 5 ml). The combined organic layers were washed with brine, dried over Na₂SO₄, filtered, and concentrated under reduced pressure to afford crude residue which was used immediately without further purification.

To a solution of galactosyl ketone (0.19 g, 0.33 mmol) in methanol (2 mL) was added sodium borohydride (26.00 mg, 0.67 mmol) in 2 portions at 0 °C. The mixture was stirred at 0 °C for 15 mins until complete consumption of starting material as observed by TLC analysis. It was diluted with 10 mL ethyl acetate and washed with water and brine, dried over anhydrous Na₂SO₄, filtered and evaporated under reduced pressure. The residual syrup was purified by silica gel column chromatography (hexane:ethyl acetate 4:1) to afford 10 and 7 stereoisomers in 22:1 ratio (combined yield: 0.18 g, 90%) as a colorless syrup. 10: [α]_D²⁰ = +11.6 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.48 – 7.44 (m, 2H), 7.43 – 7.40 (m, 2H), 7.39 – 7.28 (m, 13H), 7.05 (d, J = 7.9 Hz, 2H), 5.04 (d, J = 11.5 Hz, 1H), 4.86 (d, J = 10.3 Hz, 1H), 4.83 – 4.74 (m, 3H), 4.63 (d, J = 11.6 Hz, 1H), 4.60 (d, J = 9.6 Hz, 1H), 4.08 – 4.01 (m, 1H), 3.94 (t, J = 9.4 Hz, 1H), 3.85 (d, J = 2.6 Hz, 1H), 3.60 (dd, J = 9.2, 2.7 Hz, 1H), 3.00 (d, J = 7.5 Hz, 1H), 2.69 (s, 1H), 2.30 (s, 3H), 0.92 (d, J = 6.4 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 138.3, 138.2, 137.7, 132.6, 129.8, 128.6, 128.5, 128.4, 128.3, 127.9, 127.6, 88.0, 85.0, 83.2, 77.7, 75.8, 74.2, 73.7, 73.4, 66.9, 21.2, 17.7. HRMS (ESI): m/z calcd for C₃₅H₃₈O₅SNa [M + Na] 593.2332 found 593.2339.

p-Methylphenyl 2,3,4,6-Tetra-O-benzyl-7-deoxy-1-thio-l-glycero-α-d-galacto-heptopyranoside (11). To a solution of 10 (0.50 g, 0.87 mmol) in dry DMF (3 mL) were added sodium hydride (49.10 mg, 1.22 mmol) and BnBr (130 μL, 1.05 mmol) at 0 °C. The reaction mixture was gradually warmed to room temperature and stirred till completion with monitoring by TLC (hexane:ethyl acetate 4:1, Rf = 0.70) and then quenched with methanol (0.50 mL). It was diluted with ethyl acetate and washed with water and brine, dried over anhydrous Na₂SO₄, filtered, and evaporated under reduced pressure. The residual syrup was purified by silica gel column chromatography (hexane:ethyl acetate 4:1) to afford 11 (0.49 g, 85%) as a colorless syrup.[α]_D²⁰ = −8.8 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.51 – 7.21 (m, 22H), 6.90 (d, J = 7.9 Hz, 2H), 5.09 (d, J = 11.5 Hz, 1H), 4.87 (d, J = 10.3 Hz, 1H), 4.85 – 4.72 (m, 3H), 4.67 (d, J = 9.7 Hz, 1H), 4.67 – 4.52 (m, 3H), 3.94 (t, J = 9.5 Hz, 1H), 3.93 – 3.81 (m, 2H), 3.61 (dd, J = 9.2, 2.6 Hz, 1H), 3.31 (d, J = 8.0 Hz, 1H), 2.24 (s, 3H), 0.98 (d, J = 6.4 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.1, 138.7, 138.4, 138.3, 136.9, 131.6, 130.9, 129.6, 128.5, 128.49, 128.44, 128.3, 128.0, 127.8, 127.66, 127.63, 127.4, 88.3, 85.3, 83.4, 77.8, 75.7, 75.1, 74.2, 74.0, 73.4, 73.1, 21.1, 16.7. HRMS (ESI): m/z calcd for C₄₂H₄₄O₅SNa [M + Na] 683.2801 found 683.2784.

General protocol A for the oxidation of thioglycosides to glycosyl sulfoxides:

To a stirred solution of thioglycoside (0.35 g, 0.53 mmol) in anhydrous dichloromethane (2 mL), mCPBA (0.12 g, 0.53 mmol, 77%) was added portion-wise at −78 °C under argon. After 3h the reaction mixture was neutralized with saturated aqueous NaHCO₃ solution (2 mL) and then warmed up to room temperature. The mixture was extracted with dichloromethane (2×10 mL); all combined organic phases were washed with brine, dried over Na₂SO₄, filtered, and evaporated under reduced pressure to give crude residue. Purification by flash column chromatography on silica gel (hexane /ethyl acetate, 1:1) afforded the corresponding glycosyl sulfoxides.

p-Methylphenyl 2,3,4,6-Tetra-O-benzyl-7-deoxy-1-thio-d-glycero-α-d-galacto-heptopyranosyl sulfoxide (9). It was obtained following the general protocol A as colorless syrup (0.29 g, 81%) in a 1:1.51 ratio of two unidentified isomers.

Isomer a: White amorphous solid; [α]_D²³ = −37.3 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.50 (d, J = 7.8 Hz, 2H), 7.41 (d, J = 7.4 Hz, 2H), 7.37 – 7.21 (m, 18H), 7.16 (d, J = 7.3 Hz, 2H), 5.04 – 4.93 (m, 3H), 4.80 – 4.64 (m, 2H), 4.53 (d, J = 11.6 Hz, 1H), 4.46 (t, J = 9.6 Hz, 1H), 4.40 (d, J = 11.1 Hz, 1H), 4.17 – 4.04 (m, 2H), 3.85 (d, J = 9.8 Hz, 1H), 3.77 (dt, J = 12.2, 6.1 Hz, 1H), 3.66 (dd, J = 9.5, 2.7 Hz, 1H), 2.92 (d, J = 8.6 Hz, 1H), 2.38 (s, 3H), 0.71 (d, J = 5.9 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 141.0, 138.9, 138.3, 138.1, 138.0, 136.9, 129.4, 128.6, 128.5, 128.4, 128.3, 128.2, 128.07, 128.03, 127.9, 127.8, 127.78, 127.74, 127.6, 127.5, 127.4, 125.1, 94.7, 84.7, 82.8, 76.0, 74.6, 74.0, 73.2, 72.6, 72.3, 70.4, 21.4, 15.8. HRMS (ESI): m/z calcd for C₄₂H₄₄O₆SNa [M + Na] 699.2751 found 699.2745.

Isomer b: Colorless syrup; [α]_D²³ = −6.0 (c = 0.4, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.47 (d, J = 8.2 Hz, 2H), 7.28 (m, 16H), 7.19 (d, J = 8.1 Hz, 4H), 7.14 – 7.06 (m, 2H), 4.92 (d, J = 11.7 Hz, 1H), 4.87 (d, J = 10.7 Hz, 1H), 4.82 (d, J = 10.7 Hz, 1H), 4.72 (d, J = 11.7 Hz, 1H), 4.64 (d, J = 11.6 Hz, 1H), 4.50 (d, J = 11.2 Hz, 1H), 4.44 – 4.33 (m, 2H), 4.13 (d, J = 11.1 Hz, 1H), 4.10 (d, J = 2.5 Hz, 1H), 3.98 (t, J = 9.3 Hz, 1H), 3.75 – 3.63 (m, 2H), 3.19 (d, J = 8.6 Hz, 1H), 2.36 (s, 3H), 1.21 (d, J = 6.1 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 141.6, 139.1, 138.2, 138.07, 138.01, 137.0, 129.3, 128.56, 128.52, 128.3, 128.2, 128.1, 127.88, 127.84, 127.81, 127.78, 127.70, 127.1, 126.8, 126.3, 95.7, 84.9, 82.0, 74.7, 74.4, 74.1, 72.8, 72.6, 72.5, 70.6, 21.6, 16.5. HRMS (ESI): m/z calcd for C₄₂H₄₄O₆SNa [M + Na] 699.2751 found 699.2747.

p-Methylphenyl 2,3,4,6-Tetra-O-benzyl-7-deoxy-1-thio-l-glycero-α-d-galacto-heptopyranosyl sulfoxide (12). It was obtained following the general protocol A as colorless syrup (0.28 g, 79%) in a 1:1.63 ratio of two unidentified isomers.

Isomer a: White amorphous solid; [α]_D²³ = −109.2 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.55 (d, J = 7.9 Hz, 2H), 7.49 – 7.18 (m, 18H), 7.14 (d, J = 8.0 Hz, 2H), 7.11 – 7.03 (m, 2H), 5.11 (d, J = 11.7 Hz, 1H), 5.02 (d, J = 2.4 Hz, 2H), 4.84 (s, 2H), 4.63 – 4.50 (m, 2H), 4.12 – 4.03 (m, 2H), 3.96 (d, J = 12.0 Hz, 1H), 3.81 (d, J = 2.5 Hz, 1H), 3.79 – 3.68 (m, 2H), 3.20 (d, J = 7.8 Hz, 1H), 2.15 (s, 3H), 0.84 (d, J = 6.4 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 141.1, 139.2, 138.5, 138.04, 138.00, 136.7, 129.7, 128.68, 128.64, 128.5, 128.3, 128.2, 128.1, 128.0, 127.6, 127.2, 125.1, 94.5, 85.4, 76.1, 75.1, 74.1, 74.08, 74.02, 73.2, 73.0, 21.3, 17.1. HRMS (ESI): m/z calcd for C₄₂H₄₄O₆SNa [M + Na] 699.2751 found 699.2747.

Isomer b: White amorphous solid; [α]_D²³ = +17.1 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.48 (d, J = 8.0 Hz, 2H), 7.36 – 7.21 (m, 18H), 7.18 – 7.13 (m, 2H), 7.10 (d, J = 8.0 Hz, 2H), 5.01 (d, J = 11.7 Hz, 1H), 4.87 (s, 2H), 4.75 (d, J = 11.6 Hz, 1H), 4.69 (d, J = 11.5 Hz, 1H), 4.60 (d, J = 11.7 Hz, 1H), 4.55 – 4.45 (m, 3H), 4.12 (t, J = 9.2 Hz, 1H), 3.84 (d, J = 2.4 Hz, 1H), 3.79 (p, J = 6.5 Hz, 1H), 3.68 (dd, J = 9.1, 2.5 Hz, 1H), 3.39 (d, J = 7.6 Hz, 1H), 2.29 (s, 3H), 0.97 (d, J = 6.5 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 141.4, 139.0, 138.6, 138.1, 137.8, 137.3, 129.4, 128.6, 128.4, 128.3, 128.2, 128.0, 127.9, 127.9, 127.7, 127.6, 127.5, 127.4, 127.3, 125.9, 96.1, 85.4, 83.2, 74.9, 74.6, 74.0, 73.7, 73.5, 72.9, 21.5, 16.6. HRMS (ESI): m/z calcd for C₄₂H₄₄O₆SNa [M + Na] 699.2751 found 699.2742.

Preparation of l-glycero-α-d-gluco and d-glycero-α-d-gluco donors:

To a solution of p-methylphenyl 2,3,4-tri-O-benzyl-1-thio-β-d-glucopyranoside 13²⁰ (2.07 g, 3.70 mmol) in anhydrous DCM (20 mL) was added Dess-Martin periodinane (3.15 g, 7.40 mmol). The mixture was stirred at room temperature for 2h until complete consumption of starting material as observed by TLC analysis. The reaction was diluted with 25 ml sat. NaHCO₃, 25 ml Na₂S₂O₃ solution, the layers were separated, and the aqueous layer was extracted three times with CH₂Cl₂ (3 × 30 ml). The combined organic layers were washed with brine, dried over Na₂SO₄, filtered, and concentrated under reduced pressure to afford crude aldehyde (2.00 g) which was used immediately without further purification. Crude aldehyde was dissolved in THF (10 mL) and the solution was cooled to 0 °C. To this mixture, a solution of methyl magnesium chloride (5.41 mL, 1.0 M in THF, 5.41 mmol. 1.5 equiv.) was added in a dropwise manner over 10 mins, and the reaction mixture was stirred for 2h at same temperature. The reaction was quenched with the dropwise addition of saturated aq. NH₄Cl solution (10 mL) until effervescence stopped. Mixture was then diluted with H₂O (50 mL) and extracted with EtOAc (3 × 30 mL). Organic layer was separated, dried over Na₂SO₄ and solvents were evaporated under reduced pressure. Crude mixture was subjected to column purification (eluent: hexane/ethyl acetate) 93:7) to afford 14 (1.14 g, 54%) and 15 (0.38 g, 18%) stereoisomers in 3:1 ratio as white amorphous solid.

p-Methylphenyl 2,3,4-tri-O-benzyl-7-deoxy-1-thio-l-glycero-α-d-gluco-heptopyranoside (14). [α]²⁰_D = −4.7 (c = l.9, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.42 (m, 4H), 7.91 – 6.78 (m, 13H), 7.13 (d, J = 7.9 Hz, 2H), 5.27 – 4.84 (m, 4H), 4.78 (d, J = 10.3 Hz, 1H), 4.73 (d, J = 10.8 Hz, 1H), 4.63 (d, J = 9.6 Hz, 1H), 4.03 (qd, J = 6.6, 1.7 Hz, 1H), 3.76 – 3.67 (m, 2H), 3.47 (dt, J = 4.8, 2.7 Hz, 1H), 3.13 – 3.10 (m, 1H), 2.34 (s, 3H), 1.27 (d, J = 6.5 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 138.5, 138.2, 138.1, 138.1, 133.0, 129.8, 129.6, 128.6, 128.5, 128.4, 128.1, 128.07, 128.00, 127.9, 127.85, 127.80, 88.1, 86.7, 81.6, 81.3, 77.9, 75.8, 75.6, 75.3, 65.5, 21.2, 20.5; HRMS: m/z calc for C₃₅H₃₈O₅SNa [M+Na]⁺; 593.2332; found: 593.2318.

p-Methylphenyl 2,3,4-tri-O-benzyl-7-deoxy-1-thio-d-glycero-α-d-gluco-heptopyranoside (15). [α]²⁰_D = +9.0 (c = 0.6, CHCl₃); ¹H NMR (600 MHz, CDCl₃) δ 7.39 – 7.31 (m, 4H), 7.33 – 7.22 (m, 13H), 7.13 (d, J = 7.7 Hz, 2H), 4.97 – 4.90 (m, 3H), 4.84 (d, J = 10.9 Hz, 1H), 4.75 (d, J = 10.3 Hz, 1H), 4.65 (d, J = 11.1 Hz, 1H), 4.61 (d, J = 9.7 Hz, 1H), 3.99 (m, 1H), 3.74 (t, J = 8.8 Hz, 1H), 3.47 (td, J = 9.4, 4.3 Hz, 2H), 3.31 (dd, J = 9.8, 4.1 Hz, 1H), 2.52 (d, J = 7.0 Hz, 1H), 2.34 (s, 3H), 1.15 (d, J = 6.5 Hz, 3H); ¹³C{¹H} NMR (151 MHz, CDCl₃) δ 138.2, 138.1, 137.9, 137.5, 133.0, 129.7, 128.6, 128.56, 128.54, 128.2, 128.07, 128.00, 127.9, 127.8, 127.7, 87.7, 87.0, 81.4, 81.3, 79.4, 75.8, 75.4, 74.8, 68.1, 21.1, 17.7. HRMS: m/z calc for C₃₅H₃₈O₅SNa [M+Na]⁺; 593.2332; found: 593.2318.

p-Methylphenyl 2,3,4,6-tetra-O-benzyl-7-deoxy-1-thio-l-glycero-α-d-gluco-heptopyranoside (16). To a solution of 14 (0.34 g, 0.60 mmol) in dry DMF (2 mL) were added sodium hydride (28 mg, 0.90 mmol) and BnBr (85 μL, 0.72 mmol) at 0 °C. The reaction mixture was gradually warmed to room temperature and stirred till completion with monitoring by TLC (hexane:ethyl acetate 4:1, Rf = 0.8) and then quenched with methanol (0.50 mL). It was diluted with ethyl acetate and washed with water and brine, dried over anhydrous Na₂SO₄, filtered, and evaporated under reduced pressure. The residual syrup was purified by silica gel column chromatography (hexane:ethyl acetate 95:5) to afford 16 (0.36 g, 92%) as a colorless syrup. [α]²⁰_D +4.3 (c = 0.6, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.52 – 7.47 (m, 2H), 7.44 – 7.38 (m, 2H), 7.38 – 7.21 (m, 16H), 7.16 (dd, J = 7.6, 1.8 Hz, 2H), 7.04 (d, J = 8.0 Hz, 2H), 4.90 (dd, J = 10.5, 9.0 Hz, 2H), 4.81 (dd, J = 10.9, 5.6 Hz, 2H), 4.71 (dd, J = 11.0, 6.2 Hz, 2H), 4.54 (d, J = 9.8 Hz, 1H), 4.47 (d, J = 10.9 Hz, 1H), 4.36 (d, J = 11.7 Hz, 1H), 3.99 (qd, J = 6.3, 1.6 Hz, 1H), 3.85 (t, J = 9.3 Hz, 1H), 3.68 (t, J = 9.0 Hz, 1H), 3.49 (t, J = 9.3 Hz, 1H), 3.19 (dd, J = 9.5, 1.9 Hz, 1H), 2.31 (s, 3H), 1.34 (d, J = 6.4 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 138.9, 138.5, 138.3, 137.7, 133.1, 129.9, 129.6, 128.5, 128.5, 128.46, 128.41, 127.9, 127.9, 127.8, 127.7, 127.6, 127.5, 88.1, 87.2, 82.1, 80.9, 77.7, 75.9, 75.4, 74.9, 71.6, 70.2, 21.2, 15.6; HRMS: m/z calc for C₄₂H₄₈O₅SN [M+NH₄]⁺; 678.3231; found: 678.3234.

p-Methylphenyl 2,3,4,6-tetra-O-benzyl-7-deoxy-1-thio-d-glycero-α-d-gluco-heptopyranoside (18). To a solution of 15 (0.15 g, 0.26 mmol) in dry DMF (2 mL) were added sodium hydride (16 mg, 0.40 mmol) and BnBr (38 μL, 0.32 mmol) at 0 °C. The reaction mixture was gradually warmed to room temperature and stirred till completion with monitoring by TLC (hexane:ethyl acetate 4:1, Rf = 0.7) and then quenched with methanol (0.5 mL). It was diluted with ethyl acetate and washed with water and brine, dried over anhydrous Na₂SO₄, filtered, and evaporated under reduced pressure. The residual syrup was purified by silica gel column chromatography (hexane:ethyl acetate 95:5) to afford 18 (0.16 g, 90%) as a colorless syrup. [α]²⁰_D +3.0 (c = 0.2, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.50 – 7.45 (m, 2H), 7.39 (d, J = 7.8 Hz, 2H), 7.37 – 7.24 (m, 16H), 7.16 (dd, J = 7.3, 2.4 Hz, 2H), 7.00 (d, J = 7.9 Hz, 2H), 4.90 (dd, J = 10.6, 7.5 Hz, 2H), 4.81 (d, J = 10.8 Hz, 2H), 4.71 (d, J = 10.3 Hz, 1H), 4.65 – 4.55 (m, 4H), 4.54 (d, J = 4.7 Hz, 1H), 3.85 (qd, J = 6.6, 1.5 Hz, 1H), 3.54 (dd, J = 10.0, 1.5 Hz, 1H), 3.44 (m, 2H), 2.28 (s, 3H), 1.19 (d, J = 6.6 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.0, 138.4, 138.2, 138.0, 137.7, 132.9, 129.9, 129.7, 128.6, 128.5, 128.4, 128.3, 128.1, 127.94, 127.92, 127.8, 127.6, 127.4, 87.5, 87.4, 81.0, 80.8, 78.2, 75.9, 75.3, 74.7, 74.2, 70.9, 29.8, 21.2, 14.8; HRMS: m/z calc for C₄₂H₄₄O₅SNa [M+Na]⁺ 683.2801 found 683.2797.

General protocol B for the oxidation of thioglycosides to glucosyl sulfoxides:

To a stirred solution of thioglycoside (0.20 g, 0.30 mmol) in anhydrous dichloromethane (2 mL), mCPBA (68 mg, 0.30 mmol, 77%) was added portion-wise at −78 °C under argon followed by waring to −30 °C in 30 min. The reaction mixture was neutralized with saturated aqueous NaHCO₃ solution (5 mL) and then warmed up to room temperature. The mixture was extracted with dichloromethane (2×10 mL); all combined organic phases were washed with brine, dried over Na₂SO₄, filtered, and evaporated under reduced pressure to give crude residue. Purification by flash column chromatography on silica gel (hexane /ethyl acetate, 2:1) afforded the corresponding glucosyl sulfoxides.

p-Methylphenyl 2,3,4,6-tetra-O-benzyl-7-deoxy-1-thio-l-glycero-α-d-gluco-heptopyranosyl sulfoxide (17). It was obtained following the general protocol B as colorless syrup (0.16 g, 79%) in a 2.1:1 ratio of two unidentified isomers.

Isomer a: [α]²⁰_D = +4.4 (c = l.0, CHCl₃); ¹H NMR (600 MHz, CDCl₃) δ 7.58 (d, J = 8.0 Hz, 2H), 7.50 – 7.26 (m, 20H), 7.19 (d, J = 7.6 Hz, 2H), 4.92 – 4.80 (m, 5H), 4.76 (d, J = 10.8 Hz, 1H), 4.56–4.50 (m, 2H), 4.45 (d, J = 8.5 Hz, 1H), 4.29 (d, J = 11.5 Hz, 1H), 3.98 (q, J = 6.7 Hz, 1H), 3.82 (q, J = 8.6 Hz, 1H), 3.78 (t, J = 9.0 Hz, 1H), 3.36 (d, J = 9.4 Hz, 1H), 2.35 (s, 3H), 1.28 (d, J = 6.7 Hz, 3H); ¹³C{¹H} NMR (151 MHz, CDCl₃) δ 138.7, 138.11, 138.10, 137.9, 137.6, 129.4, 128.6, 128.57, 128.53, 128.47, 128.44, 128.38, 128.35, 128.2, 128.0, 127.9, 127.88, 127.83, 127.76, 127.72, 127.66, 127.64, 127.4, 126.6, 94.9, 86.3, 81.7, 77.3, 75.3, 74.6, 74.2, 71.5, 69.8, 21.4, 15.2; HRMS: m/z calc for C₄₂H₄₄O₆SNa [M+Na]⁺; 699.2751; found: 699.2728.

Isomer b: [α]²²_D = −15.1 (c = 0.7, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.56 (d, J = 7.9 Hz, 2H), 7.41 (d, J = 7.0 Hz, 2H), 7.39 – 7.22 (m, 18H), 7.13 (dd, J = 7.4, 2.0 Hz, 2H), 5.04 (d, J = 10.3 Hz, 1H), 4.99 – 4.93 (m, 2H), 4.89 (d, J = 11.1 Hz, 1H), 4.78 (d, J = 10.9 Hz, 1H), 4.60 (d, J = 11.8 Hz, 1H), 4.48 (d, J = 10.9 Hz, 1H), 4.30 (d, J = 11.8 Hz, 1H), 4.10 (t, J = 9.4 Hz, 1H), 3.78 (t, J = 9.1 Hz, 1H), 2.97 (dd, J = 9.5, 2.1 Hz, 1H), 2.40 (s, 3H), 0.78 (d, J = 6.5 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 141.2, 138.8, 138.4, 138.3, 137.8, 136.4, 129.5, 128.6, 128.59, 128.55, 128.47, 128.41, 128.1, 127.8, 127.75, 127.71, 127.6, 127.5, 125.3, 93.9, 87.0, 83.2, 77.4, 77.0, 75.1, 75.7, 74.9, 71.2, 69.7, 21.5, 14.5. HRMS: m/z calc for C₄₂H₄₄O₆SNa [M+Na]⁺; 699.2751; found: 699.2761.

p-Methylphenyl 2,3,4,6-tetra-O-benzyl-7-deoxy-1-thio-d-glycero-α-d-gluco-heptopyranosyl sulfoxide (19). It was obtained following the general protocol B as colorless syrup (0.16 g, 80%) in a 2.3:1 ratio of two unidentified isomers.

Isomer a. [α]²⁰_D = −55.0 (c = l.0, CHCl₃); ¹H NMR (600 MHz, CDCl₃) δ 7.60 – 7.55 (m, 2H), 7.45 – 7.40 (m, 2H), 7.40 – 7.24 (m, 16H), 7.20 (dd, J = 7.3, 2.2 Hz, 2H), 7.18 – 7.14 (m, 2H), 5.05 (d, J = 10.3 Hz, 1H), 5.01 – 4.94 (m, 2H), 4.91 (d, J = 11.1 Hz, 1H), 4.84 (d, J = 11.0 Hz, 1H), 4.66 (d, J = 11.0 Hz, 1H), 4.59 – 4.24 (m, 2H), 4.11 (t, J = 9.4 Hz, 1H), 3.92 (d, J = 9.7 Hz, 1H), 3.82 (t, J = 8.9 Hz, 1H), 3.71 (qd, J = 6.7, 1.5 Hz, 1H), 3.55 (dd, J = 9.8, 8.8 Hz, 1H), 3.35 (dd, J = 9.8, 1.5 Hz, 1H), 2.32 (s, 3H), 1.11 (d, J = 6.7 Hz, 3H); ¹³C{¹H} NMR (151 MHz, CDCl₃) δ 141.5, 138.9, 138.3, 137.7, 137.6, 136.3, 129.5, 128.54, 128.51, 128.44, 128.40, 128.2, 128.1, 127.9, 127.7, 127.6, 127.4, 127.2, 125.6, 93.1, 86.9, 81.7, 75.7, 75.6, 74.7, 74.1, 70.2, 21.4, 14.8; HRMS: m/z calc for C₄₂H₄₄O₆SNa [M+Na]⁺; 699.2751; found: 699.2729.

Isomer b. [α]²⁰_D = +7.2 (c = 0.8, CHCl₃); ¹H NMR (600 MHz, CDCl₃) δ 7.54 – 7.45 (m, 2H), 7.42 – 7.23 (m, 16H), 7.21 – 7.13 (m, 6H), 4.89 – 4.75 (m, 4H), 4.75 (d, J = 11.0 Hz, 1H), 4.62 (d, J = 11.0 Hz, 1H), 4.50 (d, J = 12.2 Hz, 1H), 4.46 (d, J = 8.9 Hz, 1H), 4.41 (d, J = 12.2 Hz, 1H), 3.88 – 3.80 (m, 2H), 3.76 (t, J = 8.5 Hz, 1H), 3.62 (dd, J = 9.6, 1.4 Hz, 1H), 3.47 (dd, J = 9.7, 8.4 Hz, 1H), 2.31 (s, 3H), 1.16 (d, J = 6.7 Hz, 3H); ¹³C{¹H} NMR (151 MHz, CDCl₃) δ 141.5, 138.7, 137.9, 137.7, 136.7, 129.5, 128.5, 128.4, 128.39, 128.32, 128.27, 128.0, 127.9, 127.9, 127.83, 127.80, 127.7, 127.69, 127.63, 127.5, 127.4, 127.3, 125.6, 95.5, 86.6, 81.5, 77.4, 76.2, 75.5, 74.7, 74.4, 74.0, 71.3, 29.7, 21.3, 15.6; HRMS: m/z calc for C₄₂H₄₄O₆SNa [M+Na]⁺; 699.2751; found: 699.2733.

p-Methoxyphenyl 2,3,4,6-Tetra-O-benzyl-7-deoxy-d-glycero-α/β-d-galacto-heptopyranoside (S1). A mixture of donor 8 (90 mg, 0.14 mmol), p-Methoxyphenol (21 mg, 0.16 mmol) and activated 4Å acid-washed powdered molecular sieves (90 mg) in anhydrous CH₂Cl₂ (1.5 mL, 0.1 M) was stirred for 30 min at rt under argon, then cooled to −40 °C. The reaction mixture was then treated with N-iodosuccinimide (37 mg, 0.16 mmol) and AgOTf (7 mg, 0.03 mmol) and stirred at −40 °C till completion, then quenched with triethylamine (20 μL) at −40 °C and gradually temperature was raised to rt. The reaction mixture was diluted with CH₂Cl₂ (5 mL), filtered through celite, and washed with 20% aqueous Na₂S₂O₃ (5 mL). The aqueous layer was extracted with CH₂Cl₂ (5 mL) twice and the combined organic layers were dried over Na₂SO₄ and concentrated under reduced pressure to afford crude residue. Purification by silica gel column chromatography eluting with ethyl acetate/ hexane (1:19 to 1:9) afforded the desired product as a colorless syrup (83 mg, 92%) in a 1:2.4 ratio of α:β anomers.

S1β:

[α]_D²³ = +30.8 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.40 (d, J = 6.8 Hz, 2H), 7.36 – 7.20 (m, 18H), 6.97 (d, J = 9.0 Hz, 2H), 6.82 – 6.78 (m, 2H), 5.44 (d, J = 3.6 Hz, 1H), 5.05 (s, 1H), 4.90 (d, J = 11.6 Hz, 1H), 4.87 – 4.76 (m, 2H), 4.71 (d, J = 12.0 Hz, 1H), 4.51 (dd, J = 11.2, 3.7 Hz, 2H), 4.27 (d, J = 2.6 Hz, 1H), 4.24 – 4.13 (m, 2H), 4.13 (dd, J = 10.0, 2.7 Hz, 1H), 3.86 – 3.73 (m, 4H), 3.65 (d, J = 9.1 Hz, 1H), 1.08 (d, J = 6.1 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 154.8, 150.8, 139.0, 138.9, 138.5, 138.4, 128.4 (2C), 128.3, 128.1, 127.9, 127.7 (2C), 127.5, 127.5, 118.1, 114.4, 96.7, 79.5, 76.2, 74.8, 74.7, 74.2, 73.5, 73.3, 72.6, 70.5, 55.7, 16.4. HRMS (ESI): m/z calcd for C₄₂H₄₄O₇Na [M + Na] 683.2979 found 683.2966.

S1α:

[α]_D²³ = −7.8 (c = 0.4, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.38 – 7.21 (m, 20H), 7.02 – 6.93 (m, 2H), 6.86 – 6.76 (m, 2H), 5.04 (d, J = 11.5 Hz, 1H), 5.00 (d, J = 10.9 Hz, 1H), 4.88 – 4.81 (m, 2H), 4.78 (d, J = 11.8 Hz, 1H), 4.74 (d, J = 11.8 Hz, 1H), 4.55 (dd, J = 11.3, 6.8 Hz, 2H), 4.23 – 4.16 (m, 2H), 4.08 (dd, J = 9.7, 7.7 Hz, 1H), 3.92 (dq, J = 8.7, 6.1 Hz, 1H), 3.76 (s, 3H), 3.59 (dd, J = 9.7, 2.8 Hz, 1H), 3.21 (d, J = 9.0 Hz, 1H), 1.31 (d, J = 6.0 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 155.1, 151.7, 139.0, 138.6, 138.6, 138.4, 128.5, 128.4, 128.39, 128.34, 128.2, 128.0, 127.9, 127.8, 127.7, 127.69, 127.64, 127.5, 127.4, 118.2, 114.5, 103.2, 82.6, 79.3, 78.0, 75.4, 74.6, 73.3, 73.1, 72.6, 70.6, 55.7, 16.7. HRMS (ESI): m/z calcd for C₄₂H₄₄O₇Na [M + Na] 683.2979 found 683.2962.

p-Methoxyphenyl 2,3-Di-O-benzyl-4,6-O-benzylidende-7-deoxy-d-glycero-β-d-galacto-heptopyranoside (S2). To a solution of the compound S1β (40 mg, 47.56 μmol) in 2 mL of MeOH under Hydrogen atmosphere (balloon pressure) was added 10% Pd/C (53 mg, 47.56 μmol) and stirred for 24h at room temperature. The reaction mixture was filtered through a pad of Celite® and the filtrate was evaporated under reduced pressure to afford crude residue which was used subsequently without purification for the next step.

To a stirred solution of unprotected galactoside (22.0 mg, 39.96 μmol) in dry acetonitrile (1.5 mL) were added pTSA (2 mg, 11.99 μmol) and benzaldehyde dimethylacetal (7.20 μL, 47.95 μmol). The reaction mixture was stirred at room temperature till completion, then quenched with triethylamine (20 μL). The reaction mixture was diluted with Ethyl acetate (10 mL) and washed with saturated solution of NaHCO₃ (5 mL). The aqueous layer was extracted with EtOAc (5 mL) twice and the combined organic layers were dried over Na₂SO₄ and concentrated under reduced pressure to afford crude residue. The crude residue obtained was dissolved in dry DMF (1.5 mL). Addition of sodium hydride (8.4 mg, 0.21 mmol) and BnBr (4.8 μL, 0.21 mmol) was done at 0 °C. The reaction mixture was gradually warmed to room temperature and stirred till completion with monitoring by TLC (hexane:ethyl acetate 4:1, Rf = 0.6) and then quenched with methanol (0.2 mL). It was diluted with ethyl acetate and washed with water and brine, dried over anhydrous Na₂SO₄, filtered, and evaporated under reduced pressure. The residual syrup was purified by silica gel column chromatography (hexane:ethyl acetate 9:1) to afford S2 (27.0 mg, 71%) as a colorless syrup.[α]_D²³ = +41.5 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.56 – 7.48 (m, 2H), 7.49 – 7.41 (m, 2H), 7.40 – 7.19 (m, 11H), 7.06 – 6.97 (m, 2H), 6.86 – 6.76 (m, 2H), 5.75 (s, 1H), 5.49 (d, J = 3.5 Hz, 1H), 4.88 (dd, J = 13.9, 12.0 Hz, 2H), 4.81 (d, J = 12.1 Hz, 1H), 4.68 (d, J = 12.0 Hz, 1H), 4.36 (dd, J = 3.3, 1.0 Hz, 1H), 4.30 – 4.18 (m, 2H), 4.16 (dd, J = 10.1, 3.3 Hz, 1H), 3.77 (s, 3H), 3.53 (s, 1H), 1.39 (d, J = 7.2 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 154.9, 151.2, 138.9, 138.5, 138.2, 128.8, 128.4 128.2, 128.0, 127.7, 127.6, 126.5, 117.7, 114.6, 97.4, 93.9, 76.3, 75.6, 73.6, 72.3, 72.2, 70.7, 66.3, 55.7, 15.3. HRMS (ESI): m/z calcd for C₃₅H₃₆O₇Na [M + Na] 591.2353 found 591.2335.

4-Methoxyphenyl 2,3,4,6-tetra-O-benzyl-7-deoxy-l-glycero-α/β-d-gluco-heptopyranoside (S3). A mixture of sulfoxide 17 (80.0 mg, 0.11 mmol), TTBP (58.7 mg, 0.23 mmol), and activated 4 Å powdered molecular sieves (160.0 mg) in CH₂Cl₂ (0.25 mL) was stirred for 1h at room temperature under argon then cooled to −78 °C and treated with Tf₂O (21.0 μL, 0.13 mmol). After stirring for 10 min, a solution of p-methoxy phenol (16.0 mg, 0.13 mmol) in CH₂Cl₂ (50 μL) was added and continued stirring for 10 h before being the reaction was quenched with triethylamine (15.0 μL) at −78 °C. The reaction mixture was diluted with dichloromethane (10 mL) and molecular sieves were filtered off through a pad of celite and filtrate was washed with saturated NaHCO₃. The organic layer was separated and dried over Na₂SO₄, filtered, and concentrated under reduced pressure. Residue was then subjected to column chromatography over silica (EtOAc/Hexane, 5:95) to afford S3β (minor compound) and S3α (major compound) as colorless syrups (Combined yield: 57. mg, 73%, α/β = 2:1, separated after column chromatography)

S3β:

[α]²⁰_D = +4.3 (c = 0.9, CHCl₃); ¹H NMR (600 MHz, CDCl₃) δ 7.42 – 7.20 (m, 18H), 7.18 – 7.13 (m, 2H), 7.03 – 6.97 (m, 2H), 6.83 – 6.79 (m, 2H), 5.44 (d, J = 3.5 Hz, 1H), 5.05 (d, J = 10.6 Hz, 1H), 4.87 (d, J = 10.6 Hz, 2H), 4.79 (d, J = 12.0 Hz, 1H), 4.66 (dd, J = 17.1, 11.8 Hz, 2H), 4.32 (dd, J = 11.3, 6.0 Hz, 2H), 4.19 (t, J = 9.3 Hz, 1H), 3.97 – 3.91 (m, 1H), 3.85 (t, J = 9.4 Hz, 1H), 3.78 (s, 3H), 3.73 (dd, J = 9.7, 3.4 Hz, 1H), 3.62 (d, J = 9.9 Hz, 1H), 1.12 (d, J = 6.4 Hz, 3H); ¹³C{¹H} NMR (151 MHz, CDCl₃) δ 154.8, 150.5, 138.6, 138.4, 138.1, 138.0, 128.5, 128.4, 128.1, 127.9, 127.7, 127.69, 127.62, 117.7, 114.4, 95.6, 82.4, 79.7, 77.5, 75.9, 74.9, 74.0, 73.3, 71.0, 70.8, 29.7, 15.6; HRMS: m/z calc for C₄₂H₄₄O₇Na [M+Na]⁺; 683.2961; found: 683.2961.

S3α:

White solid [α]²⁰_D = +10.6 (c = 0.5, CHCl₃); ¹H NMR (600 MHz, CDCl₃) δ 7.41 – 7.23 (m, 18H), 7.23 – 7.12 (m, 2H), 7.03 (m, 2H), 6.88 – 6.82 (m, 2H), 5.10 (d, J = 10.9 Hz, 1H), 4.98 (d, J = 10.8 Hz, 1H), 4.90 – 4.79 (m, 4H), 4.72 (d, J = 11.8 Hz, 1H), 4.45 (d, J = 10.8 Hz, 1H), 4.41(d, J = 11.8 Hz, 1H), 4.06 (qd, J = 6.4, 2.0 Hz, 1H), 3.96 (dd, J = 9.7, 8.7 Hz, 1H), 3.81 (s, 3H), 3.80 – 3.49 (m, 2H), 3.31 (dd, J = 9.6, 2.0 Hz, 1H), 1.40 (d, J = 6.4 Hz, 3H); ¹³C{¹H} NMR (151 MHz, CDCl₃) δ 155.2, 151.6, 138.5, 138.44, 138.42, 128.4, 128.38, 128.33, 128.0, 127.9, 127.8, 127.7, 127.67, 127.63, 127.5, 118.3, 114.5, 103.1, 85.1, 82.0, 78.1, 77.4, 75.8, 75.0, 74.8, 71.2, 70.5, 55.7, 15.7; HRMS: m/z calc for C₄₂H₄₄O₇Na [M+Na]⁺; 683.2961; found: 683.2953.

p-Methoxyphenyl 4,6-di-O-benzylidene-7-deoxy-l-glycero-α-d-gluco-heptopyranoside (S4). To a solution of the compound S3α (8.7 mg, 0.01 mmol) in MeOH (0.5 mL) under Hydrogen atmosphere (balloon pressure) was added 10% Pd/C (11 mg, 0.01 mmol) and stirred for 24h at room temperature. The reaction mixture was filtered through a pad of Celite® and the filtrate was evaporated under reduced pressure to afford crude debenzylated product (3.7 mg), which was dissolved in acetonitrile (0.2 mL) and treated with dimethyl acetal (2.6 mg, 0.02 mmol) and pTSA (1.0 mg, 4.3 μmol). Reaction was then stirred for 4 h at room temperature before being quenched with saturated aq. NaHCO₃ and extracted with EtOAc (5 mL). The organic layer was separated, collected, dried over Na₂SO₄ filtered and concentrated under reduced pressure to afford a crude residue which was purified over silica (eluent: EtOAc:Hexane, 1:3) to afford S4 as a white solid (3 mg, 61%). [α]²⁰_D = −33.3 (c = 0.2, CHCl₃); ¹H NMR (900 MHz, CDCl₃) δ 7.51 – 7.48 (m, 2H), 7.37 (m, 3H), 7.04 – 7.00 (m, 2H), 6.84 (d, J = 9.1 Hz, 2H), 5.86 (s, 1H), 4.88 (d, J = 7.7 Hz, 1H), 4.58 (p, J = 6.8 Hz, 1H), 3.90 – 3.86 (m, 2H), 3.79 (s, 3H), 3.78 – 3.74 (m, 1H), 3.72 (t, J = 7.6 Hz, 1H), 1.49 (d, J = 6.9 Hz, 3H); ¹³C{¹H} NMR (226 MHz, CDCl₃) δ 155.7, 150.9, 143.1, 137.3, 129.2, 128.4, 126.4, 118.8, 114.6, 102.5, 94.4, 77.2, 74.1, 73.9, 73.8, 70.4, 68.8, 55.6, 29.7, 11.4; HRMS: m/z calc for C₂₁H₂₄O₇Na [M+Na]⁺; 411.1414; found: 411.1400.

General procedure C for the coupling of glycosyl donors with acceptors with TTBP/Tf₂O.

A mixture of donor (1.0 equiv.), TTBP (2.0 equiv.) and activated 4 Å powdered molecular sieves (2g/mmol of donor) in CH₂Cl₂ (0.2 M in substrate) was stirred for 1h at room temperature under argon then cooled to −78 °C and treated with Tf₂O (1.1 equiv.). After 15 min. of stirring at −78 °C, a solution of the glycosyl acceptor (1.1 equiv.) in CH₂Cl₂ (0.5 M in acceptor) was added slowly. The reaction mixture was stirred for further 4–5 h. at −78 °C. and then quenched with triethylamine (0.2 mL). The reaction mixture was diluted with dichloromethane (10 mL) and molecular sieves were filtered off through a pad of celite and the filtrate was washed with saturated NaHCO₃. The organic layer was separated and dried over Na₂SO₄, filtered, and concentrated under reduced pressure. Purification by flash column chromatography on silica gel (hexane /ethyl acetate) afforded the corresponding α/β-glycopyranosides. The anomeric ratio of the products was determined by integration of the ¹H NMR spectrum of the crude product mixture.

Benzyl 2,3,4,6-tetra-O-benzyl-7-deoxy-d-glycero-α/β-d-galacto-heptopyranoside (28). 28α and 28β were obtained from the reaction of donor 9 (40.0 mg, 59.10 μmol) and benzyl alcohol (6.76 μL, 65.0 μmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 1:9); combined yield (24.0 mg, 64%), α:β = 6:1

28β :

Colorless syrup; [α]_D²³ = +15.9 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.40 – 7.19 (m, 25H), 5.02 (d, J = 11.2 Hz, 1H), 4.93 – 4.85 (m, 2H), 4.75 (d, J = 11.7 Hz, 1H), 4.71 (dd, J = 12.1, 5.6 Hz, 2H), 4.57 (d, J = 1.7 Hz, 1H), 4.55 (d, J = 2.5 Hz, 1H), 4.51 (d, J = 7.3 Hz, 1H), 4.48 (d, J = 6.4 Hz, 1H), 4.24 (d, J = 2.6 Hz, 1H), 4.20 (d, J = 11.1 Hz, 1H), 4.04 (dd, J = 10.1, 3.5 Hz, 1H), 4.00 (dd, J = 10.1, 2.5 Hz, 1H), 3.83 (dq, J = 9.1, 6.0 Hz, 1H), 3.62 (d, J = 9.1 Hz, 1H), 1.30 (d, J = 6.0 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.1, 139.0, 138.6, 138.4, 137.1, 128.5, 128.4, 128.39, 128.33, 128.2, 127.96, 127.90, 127.8, 127.7, 127.5, 127.48, 127.42, 95.6, 79.7, 76.4, 74.8, 74.7, 73.7, 73.3, 73.2, 72.8, 70.6, 68.6, 16.5. HRMS (ESI): m/z calcd for C₄₂H₄₄O₆Na [M + Na] 667.3030 found 667.3016.

28α:

Colorless syrup; [α]_D²³ = −21.7 (c = 0.6, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.36 (d, J = 6.9 Hz, 2H), 7.37 – 7.17 (m, 23H), 5.01 (d, J = 11.4 Hz, 1H), 4.93 (dd, J = 11.4, 5.4 Hz, 2H), 4.80 – 4.71 (m, 2H), 4.70 (d, J = 11.9 Hz, 1H), 4.65 (d, J = 12.0 Hz, 1H), 4.55 (d, J = 3.4 Hz, 1H), 4.43 (d, J = 7.7 Hz, 1H), 4.17 (d, J = 11.2 Hz, 1H), 4.13 (d, J = 2.8 Hz, 1H), 3.98 – 3.84 (m, 2H), 3.51 (dd, J = 9.7, 2.9 Hz, 1H), 3.10 (d, J = 8.8 Hz, 1H), 1.33 (d, J = 6.0 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.1, 138.8, 138.7, 138.4, 137.6, 128.5, 128.44, 128.41, 128.3, 128.2, 128.0, 127.8, 127.7, 127.5, 127.4, 103.0, 95.5, 82.8, 79.6, 77.8, 75.2, 74.6, 73.4, 73.2, 72.7, 70.9, 70.6, 16.6. HRMS (ESI): m/z calcd for C₄₂H₄₄O₆Na [M + Na] 667.3030 found 667.3021.

Isopropyl 2,3,4,6-Tetra-O-benzyl-7-deoxy-d-glycero-α-d-galacto-heptopyranoside (29α). 29α and 29β were obtained from the reaction of donor 9 (40.0 mg, 59.10 μmol) and isopropyl alcohol (5.0 μL, 65.00 μmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 1:9); combined yield (26.0 mg, 73%), α:β = 16.7:1

Only 29α data given here : Colorless syrup; [α]_D²² = −4.0 (c = 0.2, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.38 – 7.19 (m, 20H), 4.99 (d, J = 11.5 Hz, 1H), 4.92 (d, J = 10.7 Hz, 1H), 4.80 – 4.66 (m, 3H), 4.53 (dd, J = 11.4, 7.2 Hz, 2H), 4.38 (d, J = 7.7 Hz, 1H), 4.15 (d, J = 11.1 Hz, 1H), 4.11 (d, J = 2.8 Hz, 1H), 3.97 (hept, J = 6.2 Hz, 1H), 3.88 (dq, J = 9.0, 6.0 Hz, 1H), 3.79 (dd, J = 9.8, 7.7 Hz, 1H), 3.50 (dd, J = 9.8, 2.9 Hz, 1H), 3.08 (d, J = 8.8 Hz, 1H), 1.29 (d, J = 6.0 Hz, 3H), 1.27 (d, J = 6.3 Hz, 3H), 1.23 (d, J = 6.1 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.1, 138.9, 138.8, 138.5, 128.4, 128.39, 128.33, 128.17, 128.14, 128.0, 127.8, 127.7, 127.56, 127.52, 127.3, 103.0, 82.8, 79.7, 77.8, 75.2, 74.5, 73.5, 73.2, 72.8, 72.5, 70.6, 23.6, 22.3, 16.6. HRMS (ESI): m/z calcd for C₃₈H₄₄O₆Na [M + Na] 619.3030 found 619.3030.

Adamantyl 2,3,4,6-tetra-O-benzyl-7-deoxy-d-glycero-α/β-d-galacto-heptopyranoside (30). 30α and 30β were obtained from the reaction of donor 9 (30.0 mg, 44.30 μmol) and 1-adamantanol (7.4 mg, 48.7 μmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 1:19); combined yield (24.1 mg, 79%), α:β = 14.2:1

30β:

Colorless syrup; [α]_D²² = +33.2 (c = 0.4, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.37 – 7.18 (m, 20H), 5.31 (d, J = 3.7 Hz, 1H), 5.01 (d, J = 11.2 Hz, 1H), 4.82 (d, J = 11.6 Hz, 1H), 4.77 – 4.66 (m, 3H), 4.56 (d, J = 11.1 Hz, 1H), 4.47 (d, J = 11.2 Hz, 1H), 4.26 – 4.18 (m, 2H), 4.03 (dd, J = 10.2, 3.7 Hz, 1H), 3.97 (dd, J = 10.2, 2.7 Hz, 1H), 3.87 – 3.76 (m, 2H), 2.13 (p, J = 3.2 Hz, 3H), 1.90 – 1.83 (m, 3H), 1.80 – 1.70 (m, 3H), 1.66 – 1.57 (m, 6H), 1.27 (d, J = 5.6 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.3, 139.2, 138.9, 138.6, 128.5, 128.3, 128.2, 128.0, 127.84, 127.81, 127.6, 127.5, 127.3, 127.3, 90.5, 79.6, 76.4, 75.0, 74.7, 74.3, 73.3, 73.2, 73.1, 72.8, 70.7, 42.7, 36.4, 30.7, 16.8. HRMS (ESI): m/z calcd for C₄₅H₅₂O₆Na [M + Na] 711.3656 found 711.3649.

30α:

Colorless syrup; [α]_D²² = +6.8 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.41 – 7.20 (m, 20H), 5.01 (d, J = 11.5 Hz, 1H), 4.97 (d, J = 10.9 Hz, 1H), 4.79 – 4.73 (m, 2H), 4.71 (d, J = 11.9 Hz, 1H), 4.61 (d, J = 7.8 Hz, 1H), 4.55 (d, J = 6.8 Hz, 1H), 4.53 (d, J = 6.3 Hz, 1H), 4.17 (d, J = 11.2 Hz, 1H), 4.12 (d, J = 2.8 Hz, 1H), 3.89 (dq, J = 8.9, 6.0 Hz, 1H), 3.80 (dd, J = 9.7, 7.7 Hz, 1H), 3.10 (d, J = 9.1 Hz, 1H), 2.15 (t, J = 3.3 Hz, 3H), 1.98 – 1.89 (m, 3H), 1.85 – 1.73 (m, 3H), 1.71 – 1.57 (m, 6H), 1.29 (d, J = 6.0 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.2, 139.0, 138.9, 138.6, 128.4, 128.39, 128.32, 128.16, 128.13, 127.8, 127.7, 127.57, 127.53, 127.50, 127.3, 96.9, 83.1, 79.6, 77.8, 75.3, 74.9, 74.6, 73.6, 73.2, 72.7, 70.6, 42.8, 36.4, 30.8, 16.8. HRMS (ESI): m/z calcd for C₄₅H₅₂O₆Na [M + Na] 711.3656 found 711.3638.

Methyl 2,3,4-Tri-O-benzyl-6-O-(2,3,4,6-tetra-O-benzyl-7-deoxy-d-glycero-α/β-d-galacto-heptopyranosyl)-α-d-glucopyranoside (31). 31α and 31β were obtained from the reaction of donor 9 (30.0 mg, 44.30 μmol) and acceptor 23 (22.7 mg, 48.8 μmol)²⁰ following the general procedure for glycosylation (Ethyl acetate/hexane, 1:4); combined yield (31.0 mg, 70%), α:β = 4.0:1

31β :

Colorless syrup; [α]_D²² = +32.0 (c = 0.5, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.35 – 7.17 (m, 35H), 5.01 – 4.98 (m, 2H), 4.95 (d, J = 10.9 Hz, 1H), 4.85 (d, J = 11.0 Hz, 1H), 4.80 (d, J = 4.0 Hz, 1H), 4.78 (d, J = 5.0 Hz, 1H), 4.72 – 4.65 (m, 4H), 4.59 (d, J = 11.0 Hz, 1H), 4.55 (d, J = 5.4 Hz, 1H), 4.54 – 4.51 (m, 2H), 4.48 (d, J = 11.3 Hz, 1H), 4.20 (d, J = 11.3 Hz, 1H), 4.16 (d, J = 2.8 Hz, 1H), 4.03 (dd, J = 10.0, 3.6 Hz, 1H), 3.96 (t, J = 9.2 Hz, 1H), 3.89 (dd, J = 10.1, 2.8 Hz, 1H), 3.83 – 3.71 (m, 3H), 3.68 (d, J = 10.4 Hz, 1H), 3.59 (t, J = 9.4 Hz, 1H), 3.52 (d, J = 9.1 Hz, 1H), 3.40 (dd, J = 9.6, 3.6 Hz, 1H), 3.28 (s, 3H), 1.21 (d, J = 5.9 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.2, 139.0, 138.9, 138.6, 138.4, 138.3, 128.47, 128.43, 128.3, 128.2, 128.1, 128.0, 128.0, 127.95, 127.90, 127.7, 127.66, 127.62, 127.5, 127.4, 127.3, 97.9, 97.8, 82.1, 80.3, 78.9, 78.0, 76.5, 75.7, 75.1, 74.8, 74.7, 73.6, 73.4, 72.89, 72.84, 72.53, 70.50, 70.3, 66.0, 55.1, 16.4. HRMS (ESI): m/z calcd for C₆₃H₆₈O₁₁Na [M + Na] 1023.4653 found 1023.4644.

31α:

Colorless syrup; [α]_D²² = +12.1 (c = 1.1, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.39 – 7.15 (m, 35H), 5.04 – 4.89 (m, 3H), 4.83 – 4.67 (m, 6H), 4.65 (d, J = 12.1 Hz, 1H), 4.60 (d, J = 3.5 Hz, 1H), 4.52 (q, J = 10.8 Hz, 3H), 4.27 (d, J = 7.7 Hz, 1H), 4.20–4.14 (m, 2H), 4.11 (s, 1H), 3.98 (t, J = 9.1 Hz, 1H), 3.87 (dt, J = 16.6, 7.8 Hz, 3H), 3.60 (dd, J = 10.7, 5.5 Hz, 1H), 3.56 – 3.42 (m, 3H), 3.32 (s, 3H), 3.06 (d, J = 8.7 Hz, 1H), 1.27 (d, J = 6.2 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.1, 139.0, 138.8, 138.6, 138.5, 138.4, 138.2, 128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 127.97, 127.91, 127.86, 127.81, 127.7, 127.6, 127.5, 127.4, 127.3, 104.7, 98.0, 82.8, 82.2, 80.0, 79.4, 78.2, 77.8, 75.7, 75.2, 74.9, 74.6, 73.5, 73.4, 73.0, 72.7, 70.6, 70.3, 70.0, 68.8, 55.2, 16.6. HRMS (ESI): m/z calcd for C₆₃H₆₈O₁₁Na [M + Na] 1023.4653 found 1023.4642.

6-O-(2,3,4,6-Tetra-O-benzyl-7-deoxy-d-glycero-α/β-d-galacto-heptopyranosyl)-1,2:3,4-O-diisopropylidene-α-d-galactopyranose (32). 32α and 32β were obtained from the reaction of donor 9 (30.0 mg, 44.30 μmol) and acceptor 24 (12.7 mg, 48.80 μmol)³⁵ following the general procedure for glycosylation (Ethyl acetate/hexane, 1:4); combined yield (22.0 mg, 62%), α:β = 3.2:1.

32β :

Colorless syrup; [α]_D²² = +2.8 (c = 0.5, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.38 – 7.18 (m, 20H), 5.51 (d, J = 5.1 Hz, 1H), 5.02 (d, J = 3.7 Hz, 1H), 4.99 (d, J = 11.3 Hz, 1H), 4.83 (d, J = 11.7 Hz, 1H), 4.78 – 4.69 (m, 3H), 4.61 – 4.52 (m, 2H), 4.49 (d, J = 11.2 Hz, 1H), 4.34 (dd, J = 8.0, 1.9 Hz, 1H), 4.26 – 4.16 (m, 2H), 4.10 – 3.98 (m, 2H), 3.95 (dd, J = 10.1, 2.7 Hz, 1H), 3.87 – 3.72 (m, 2H), 3.66 (dd, J = 10.3, 7.7 Hz, 1H), 3.61 (d, J = 8.8 Hz, 1H), 1.53 (s, 3H), 1.43 (s, 3H), 1.32 (s, 3H), 1.32 – 1.26 (m, 6H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.2, 139.1, 138.8, 138.6, 128.4, 128.36, 128.32, 128.2, 127.9, 127.8, 127.7, 127.6, 127.5, 127.4, 127.3, 109.2, 108.6, 97.6, 96.3, 79.5, 76.3, 74.75, 74.72, 73.5, 73.0, 72.8, 72.7, 70.8, 70.7, 70.5, 65.8, 65.7, 26.2, 26.1, 24.9, 24.7, 16.4. HRMS (ESI): m/z calcd for C₄₇H₅₆O₁₁Na [M + Na] 819.3714 found 819.3716.

32α:

Colorless syrup; [α]_D²² = ˗32.7 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.45 – 7.41 (m, 2H), 7.35 – 7.19 (m, 18H), 5.55 (d, J = 5.0 Hz, 1H), 5.03 (d, J = 11.1 Hz, 1H), 4.99 (d, J = 11.4 Hz, 1H), 4.80 (d, J = 11.9 Hz, 1H), 4.76 – 4.68 (m, 2H), 4.58 (dd, J = 7.9, 2.4 Hz, 1H), 4.53 (dd, J = 11.3, 6.5 Hz, 2H), 4.39 (d, J = 7.7 Hz, 1H), 4.30 (dd, J = 5.0, 2.4 Hz, 1H), 4.22 (dd, J = 7.9, 1.8 Hz, 1H), 4.17 (d, J = 11.1 Hz, 1H), 4.15 – 4.04 (m, 3H), 3.93 – 3.78 (m, 2H), 3.69 (dd, J = 10.1, 7.0 Hz, 1H), 3.51 (dd, J = 9.7, 2.8 Hz, 1H), 3.10 (d, J = 8.6 Hz, 1H), 1.50 (s, 3H), 1.44 (s, 3H), 1.32 – 1.27 (m, 9H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.16, 139.12, 138.8, 138.4, 128.6, 128.5, 128.3, 128.19, 128.12, 128.0, 127.8, 127.7, 127.54, 127.50, 127.3, 109.4, 108.7, 105.1, 96.5, 82.4, 79.1, 77.7, 74.7, 74.6, 73.5, 73.2, 72.7, 71.5, 70.9, 70.6, 69.4, 67.4, 26.1, 26.0, 25.1, 24.5, 16.6. HRMS (ESI): m/z calcd for C₄₇H₅₆O₁₁Na [M + Na] 819.3714 found 819.3725.

Methyl 4-O-(2,3,4,6-Tetra-O-benzyl-7-deoxy-d-glycero-α/β-d-galacto-heptopyranosyl)-2,3-O-isopropylidene-α-L-rhamnopyranoside (33). 33α and 33β were obtained from the reaction of 9 (40.0 mg, 59.10 μmol) and acceptor 25 (14.2 mg, 65.00 μmol)³⁶ following the general procedure for glycosylation (Ethyl acetate/hexane, 1:9); combined yield (34.3 mg, 77%), α:β = 5.1:1

33β:

Colorless syrup; [α]_D²² = +21.5 (c = 0.4, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.37 – 7.20 (m, 20H), 5.08 (d, J = 3.7 Hz, 1H), 5.02 (d, J = 11.3 Hz, 1H), 4.83 – 4.72 (m, 4H), 4.67 (d, J = 11.8 Hz, 1H), 4.57 (d, J = 11.2 Hz, 1H), 4.47 (d, J = 11.3 Hz, 1H), 4.25 – 4.20 (m, 2H), 4.14 (t, J = 6.4 Hz, 1H), 4.11 – 4.03 (m, 2H), 3.92 (dd, J = 10.2, 2.7 Hz, 1H), 3.86 (dq, J = 9.1, 6.0 Hz, 1H), 3.74 (d, J = 9.0 Hz, 1H), 3.66 (dq, J = 9.9, 6.3 Hz, 1H), 3.34 (s, 3H), 3.29 (dd, J = 9.9, 6.7 Hz, 1H), 1.46 (s, 3H), 1.34 – 1.31 (m, 6H), 1.28 (s, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.3, 138.9, 138.7, 138.6, 128.4, 128.3, 128.2, 128.1, 127.7, 127.65, 127.61, 127.4, 127.3, 127.2, 109.1, 99.2, 98.2, 82.9, 79.4, 76.6, 75.6, 74.9, 74.6, 74.1, 73.9, 73.3, 72.6, 70.5, 64.6, 54.7, 28.0, 26.1, 17.9, 16.4. HRMS (ESI): m/z calcd for C₄₅H₅₄O₁₀Na [M + Na] 777.3609 found 777.3600.

33α:

Colorless syrup; [α]_D²² = ˗8.0 (c = 0.9, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.37 (d, J = 7.8 Hz, 2H), 7.36 – 7.19 (m, 18H), 5.01 (d, J = 11.5 Hz, 1H), 4.89 (d, J = 11.0 Hz, 1H), 4.83 (d, J = 9.4 Hz, 2H), 4.81 – 4.65 (m, 3H), 4.55–4.50 (m, 2H), 4.25 – 4.15 (m, 2H), 4.12 – 4.04 (m, 2H), 3.89 (dq, J = 8.1, 6.0 Hz, 1H), 3.73 (dd, J = 9.8, 7.6 Hz, 1H), 3.60 (qd, J = 10.0, 5.5 Hz, 2H), 3.54 (dd, J = 9.7, 2.9 Hz, 1H), 3.38 (s, 3H), 3.09 (d, J = 8.7 Hz, 1H), 1.48 (s, 3H), 1.35 – 1.26 (m, 9H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.3, 139.0, 138.9, 138.4, 128.5, 128.3, 128.2, 128.2, 127.8, 127.75, 127.72, 127.5, 127.4, 127.3, 109.3, 102.5, 98.1, 82.8, 79.8, 78.8, 78.3, 77.7, 75.9, 75.1, 74.6, 73.9, 73.3, 72.8, 70.6, 64.3, 54.9, 28.0, 26.3, 18.1, 16.7. HRMS (ESI): m/z calcd for C₄₅H₅₄O₁₀Na [M + Na] 777.3609 found 777.3607.

Methyl 2,3,6-tri-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-7-deoxy-d-glycero-α/β-d-galacto-heptopyranosyl)-α-d-glucopyranoside (34). 34α and 34β were obtained from the reaction of 9 (30.0 mg, 44.30 μmol) and acceptor 26 (22.7 mg, 48.80 μmol)³⁷ following the general procedure for glycosylation (Ethyl acetate/hexane, 1:4); combined yield (25.0 mg, 55%), α:β = 2.1:1

34β:

Colorless syrup; [α]_D²² = +14.0 (c = 0.8, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.36 – 7.12 (m, 35H), 5.73 (d, J = 3.8 Hz, 1H), 4.96 (d, J = 4.6 Hz, 1H), 4.94 (d, J = 4.3 Hz, 1H), 4.80 (d, J = 11.4 Hz, 1H), 4.68 (d, J = 12.0 Hz, 2H), 4.64 (d, J = 11.2 Hz, 2H), 4.65 – 4.50 (m, 6H), 4.46 (t, J = 11.4 Hz, 2H), 4.22 (d, J = 11.2 Hz, 1H), 4.16 (d, J = 3.7 Hz, 1H), 4.07 – 4.03 (m, 1H), 4.01 (dd, J = 10.3, 3.8 Hz, 1H), 3.92 – 3.87 (m, 1H), 3.86 – 3.78 (m, 2H), 3.75 (dd, J = 10.3, 2.6 Hz, 1H), 3.68 (dd, J = 10.3, 2.5 Hz, 1H), 3.61 – 3.52 (m, 2H), 3.47 (d, J = 8.9 Hz, 1H), 3.38 (s, 3H), 1.28 (d, J = 6.1 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.0, 138.9, 138.8, 138.7, 138.3, 138.1, 138.0, 128.5, 128.4, 128.3, 128.29, 128.22, 128.1, 128.0, 127.7, 127.67, 127.61, 127.5, 127.4, 127.3, 127.2, 127.0, 97.7, 97.0, 82.2, 80.3, 79.5, 75.6, 74.8, 74.7, 74.4, 74.1, 73.8, 73.5, 73.1, 72.9, 72.6, 70.5, 69.8, 69.4, 55.1, 16.4. HRMS (ESI): m/z calcd for C₆₃H₆₈O₁₁Na [M + Na] 1023.4653 found 1023.4657.

34α:

Colorless syrup; [α]_D²² = −3.1 (c = 1.1, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.39 – 7.19 (m, 32H), 7.19 – 7.15 (m, 1H), 7.15 – 7.10 (m, 2H), 5.12 – 5.00 (m, 2H), 4.86 (d, J = 12.2 Hz, 1H), 4.79 (s, 2H), 4.75 – 4.63 (m, 4H), 4.59 (d, J = 3.7 Hz, 1H), 4.55 (d, J = 12.0 Hz, 1H), 4.47 (dd, J = 11.4, 2.0 Hz, 2H), 4.38 (d, J = 12.0 Hz, 1H), 4.27 (d, J = 7.6 Hz, 1H), 4.17 (d, J = 11.2 Hz, 1H), 4.10 (d, J = 2.8 Hz, 1H), 3.91 (d, J = 9.2 Hz, 1H), 3.88 – 3.77 (m, 2H), 3.76 (dd, J = 9.7, 7.7 Hz, 1H), 3.71 – 3.57 (m, 2H), 3.55 – 3.45 (m, 2H), 3.38 (s, 3H), 3.34 (dd, J = 9.7, 2.9 Hz, 1H), 2.92 (s, 1H), 1.09 (d, J = 5.9 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.7, 139.5, 139.1, 138.8, 138.7, 138.6, 138.0, 128.49, 128.46, 128.42, 128.37, 128.30, 128.2, 128.1, 128.0, 127.9, 127.89, 127.86, 127.77, 127.72, 127.70, 127.5, 127.45, 127.43, 127.3, 127.2, 126.9, 102.9, 98.6, 83.0, 80.4, 80.2, 79.0, 77.6, 76.5, 75.5, 75.2, 74.5, 73.8, 73.6, 73.3, 72.8, 72.7, 70.5, 70.0, 67.9, 55.4, 16.5. HRMS (ESI): m/z calcd for C₆₃H₆₈O₁₁Na [M + Na] 1023.4653 found 1023.4653.

3-O-(2,3,4,6-Tetra-O-benzyl-7-deoxy-d-glycero-α/β-d-galacto-heptopyranosyl)-1,2:5,6-di-O-isopropylidene-α-d-glucofuranose (35). 35α and 35β were obtained from the reaction of 9 (30.0 mg, 44.30 μmol) and acceptor 27 (12.7 mg, 48.80 μmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 1:4); combined yield (25.0 mg, 68%), α:β = 1:2.9

35β:

Colorless syrup; [α]_D²² = +32.7 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.37 – 7.31 (m, 8H), 7.30 – 7.21 (m, 12H), 5.88 (d, J = 3.5 Hz, 1H), 5.30 (d, J = 3.8 Hz, 1H), 5.03 (d, J = 11.2 Hz, 1H), 4.82 (d, J = 11.7 Hz, 1H), 4.79 – 4.70 (m, 3H), 4.59 (dd, J = 7.3, 3.7 Hz, 2H), 4.51 – 4.44 (m, 2H), 4.27 – 4.20 (m, 3H), 4.16 – 4.07 (m, 2H), 4.06 – 3.98 (m, 2H), 3.95 – 3.79 (m, 2H), 3.57 (d, J = 9.0 Hz, 1H), 1.48 (s, 3H), 1.40 (s, 3H), 1.35 (d, J = 6.0 Hz, 3H), 1.27 (s, 3H), 1.24 (s, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.0, 138.8, 138.6, 138.2, 128.6, 128.4, 128.36, 128.32, 127.9, 127.89, 127.80, 127.7, 127.6, 127.5, 127.48, 127.42, 111.8, 109.1, 105.2, 98.6, 84.1, 81.4, 80.0, 79.2, 76.3, 74.8, 74.7, 74.4, 73.5, 73.0, 72.9, 72.3, 70.9, 67.2, 27.1, 26.9, 26.3, 25.5, 16.6. HRMS (ESI): m/z calcd for C₄₇H₅₆O₁₁Na [M + Na] 819. 3714 found 819.3703.

35α:

Colorless syrup; [α]_D²² = −2.2 (c = 0.8, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.34 – 7.22 (m, 20H), 5.75 (d, J = 3.7 Hz, 1H), 5.00 (d, J = 11.6 Hz, 1H), 4.79 (d, J = 11.1 Hz, 1H), 4.74 – 4.65 (m, 3H), 4.55 (d, J = 11.2 Hz, 1H), 4.53 – 4.47 (m, 2H), 4.45 – 4.36 (m, 2H), 4.34 (dd, J = 4.8, 3.1 Hz, 1H), 4.23 (d, J = 3.1 Hz, 1H), 4.20 (d, J = 11.1 Hz, 1H), 4.12 (d, J = 2.7 Hz, 1H), 4.10 – 4.02 (m, 2H), 3.87 (dq, J = 8.8, 6.1 Hz, 1H), 3.73 (dd, J = 9.7, 7.7 Hz, 1H), 3.51 (dd, J = 9.6, 2.8 Hz, 1H), 3.10 (d, J = 8.6 Hz, 1H), 1.47 (s, 3H), 1.42 (s, 3H), 1.34 (s, 3H), 1.29 (d, J = 6.0 Hz, 3H), 1.21 (s, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.1, 138.5, 138.4, 138.3, 129.7, 128.5, 128.4, 128.2, 127.87, 127.81, 127.7, 127.6, 127.58, 127.51, 127.4, 111.8, 108.5, 105.2, 102.5, 82.8, 82.7, 80.9, 80.4, 79.4, 78.0, 75.3, 74.5, 73.5, 73.0, 72.7, 70.6, 65.9, 26.7, 26.6, 26.1, 25.4, 16.5. HRMS (ESI): m/z calcd for C₄₇H₅₆O₁₁Na [M + Na] 819. 3714 found 819.3703.

Benzyl 2,3,4,6-tetra-O-benzyl-7-deoxy-l-glycero-α/β-d-galacto-heptopyranoside (36). 36α and 36β were obtained from the reaction of donor 12 (25.0 mg, 36.90 μmol) and benzyl alcohol (4.2 μL, 40.60 μmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 1:9); combined yield (12.6 mg, 53%), α:β = 1.6:1.

36β :

Colorless syrup; [α]_D²¹ = +64.4 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.43 – 7.21 (m, 25H), 5.08 (d, J = 11.5 Hz, 1H), 4.97 – 4.91 (m, 2H), 4.81 – 4.72 (m, 3H), 4.70 (d, J = 12.0 Hz, 1H), 4.64 (d, J = 11.6 Hz, 1H), 4.61 – 4.55 (m, 3H), 4.08 (dd, J = 10.0, 3.7 Hz, 1H), 4.02 (dd, J = 10.1, 2.6 Hz, 1H), 3.91 (d, J = 2.6 Hz, 1H), 3.83 – 3.73 (m, 2H), 0.99 (d, J = 6.1 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.4, 138.9, 138.7, 138.6, 137.3, 128.6, 128.48, 128.41, 128.3, 128.2, 127.9, 127.8, 127.69, 127.63, 127.59, 127.55, 127.4, 94.6, 80.3, 76.6, 75.7, 75.56, 75.50, 74.3, 73.8, 73.0, 68.0, 16.7. HRMS (ESI): m/z calcd for C₄₂H₄₄O₆Na [M + Na] 667.3030 found 667.3023.

36α:

Colorless syrup; [α]_D²¹ = −12.4 (c = 0.6, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.45 – 7.19 (m, 25H), 5.07 (d, J = 11.6 Hz, 1H), 5.01 – 4.93 (m, 2H), 4.83 (d, J = 11.7 Hz, 1H), 4.80 – 4.73 (m, 3H), 4.70 – 4.60 (m, 3H), 4.47 (d, J = 7.7 Hz, 1H), 3.94 (dd, J = 9.8, 7.7 Hz, 1H), 3.87 (dq, J = 8.2, 6.3 Hz, 1H), 3.78 (d, J = 2.8 Hz, 1H), 3.52 (dd, J = 9.8, 2.8 Hz, 1H), 3.24 (d, J = 8.2 Hz, 1H), 0.92 (d, J = 6.3 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.2, 138.7, 138.5, 137.7, 128.5, 128.4, 128.3, 127.9, 127.75, 127.70, 127.6, 127.5, 102.8, 83.3, 79.8, 79.7, 75.2, 74.1, 74.1, 73.7, 73.3, 70.8, 16.8. HRMS (ESI): m/z calcd for C₄₂H₄₄O₆Na [M + Na] 667.3030 found 667.3021.

Isopropyl 2,3,4,6-tetra-O-benzyl-7-deoxy-l-glycero-α/β-d-galacto-heptopyranoside (37). 37α and 37β were obtained from the reaction of donor 12 (40.0 mg, 59.10 μmol) and isopropyl alcohol (5.0 μL, 65.00 μmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 1:9); combined yield (20.0 mg, 58%), α:β = 5.9:1

37β:

Colorless syrup; [α]_D²³ = +20.9 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.41 – 7.38 (m, 2H), 7.38 – 7.32 (m, 4H), 7.32 – 7.21 (m, 14H), 5.08 (d, J = 11.4 Hz, 1H), 5.01 (d, J = 3.8 Hz, 1H), 4.92 (d, J = 11.5 Hz, 1H), 4.84 – 4.73 (m, 2H), 4.68 (d, J = 11.4 Hz, 2H), 4.57 (dd, J = 11.6, 3.6 Hz, 2H), 4.07 (dd, J = 10.1, 3.9 Hz, 1H), 4.00 – 3.93 (m, 2H), 3.90 (dd, J = 2.7, 1.0 Hz, 1H), 3.78 – 3.70 (m, 2H), 1.21 (d, J = 6.3 Hz, 3H), 1.17 (d, J = 6.1 Hz, 3H), 0.98 (d, J = 5.9 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.5, 139.0, 138.83, 138.80, 128.45, 128.41, 128.3, 128.2, 128.1, 127.7, 127.6, 127.55, 127.50, 127.2, 94.9, 80.2, 76.7, 75.9, 75.5, 75.4, 74.3, 73.7, 73.2, 73.0, 68.7, 23.2, 21.1, 16.8. HRMS (ESI): m/z calcd for C₃₈H₄₄O₆Na [M + Na] 619.3030 found 619.3036.

37α:

Colorless syrup; [α]_D²³ = +3.2 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.38 – 7.35 (m, 4H), 7.35 – 7.23 (m, 16H), 5.05 (d, J = 11.6 Hz, 1H), 4.96 (d, J = 10.8 Hz, 1H), 4.84 (d, J = 11.7 Hz, 1H), 4.79 – 4.68 (m, 3H), 4.60 (dd, J = 11.6, 10.0 Hz, 2H), 4.42 (d, J = 7.8 Hz, 1H), 4.04 (hept, J = 6.1 Hz, 1H), 3.88 – 3.79 (m, 2H), 3.75 (dd, J = 2.8, 1.1 Hz, 1H), 3.51 (dd, J = 9.8, 2.8 Hz, 1H), 3.22 (dd, J = 8.3, 1.0 Hz, 1H), 1.30 (d, J = 6.2 Hz, 3H), 1.22 (d, J = 6.1 Hz, 3H), 0.89 (d, J = 6.4 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.2, 138.9, 138.7, 128.5, 128.4, 128.37, 128.34, 128.30, 127.7, 127.69, 127.63, 127.60, 127.4, 102.5, 83.5, 79.7, 79.6, 75.24, 75.21, 74.2, 74.1, 73.8, 73.3, 72.1, 23.8, 22.2, 16.8. HRMS (ESI): m/z calcd for C₃₈H₄₄O₆Na [M + Na] 619.3030 found 619.3016.

Adamantyl 2,3,4,6-tetra-O-benzyl-7-deoxy-l-glycero-α/β-d-galacto-heptopyranoside (38). 38α and 38β were obtained from the reaction of donor 12 (40.0 mg, 59.10 μmol) and 1-adamantanol (9.9 mg, 65.00 μmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 1:19); combined yield (20.0 mg, 70%), α:β = 4.1:1

38β:

Colorless syrup; [α]_D²³ = +23.1 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.41 – 7.19 (m, 20H), 5.38 (d, J = 3.9 Hz, 1H), 5.10 (d, J = 11.5 Hz, 1H), 4.89 (d, J = 11.5 Hz, 1H), 4.77 (d, J = 11.5 Hz, 1H), 4.72 (d, J = 4.1 Hz, 2H), 4.65 (d, J = 11.3 Hz, 1H), 4.55 (dd, J = 11.5, 2.8 Hz, 2H), 4.06 (dd, J = 10.2, 3.8 Hz, 1H), 3.98 (dd, J = 10.0, 2.7 Hz, 1H), 3.92 – 3.87 (m, 2H), 3.74 (p, J = 6.4 Hz, 1H), 2.14 – 2.00 (m, 3H), 1.96 – 1.85 (m, 3H), 1.79 (dd, J = 9.0, 5.7 Hz, 3H), 1.54 (s, 6H), 1.02 (d, J = 6.3 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.3, 139.1, 138.97, 138.90, 128.4, 128.35, 128.30, 128.2, 128.1, 128.0, 127.6, 127.57, 127.55, 127.54, 127.46, 127.44, 127.2, 90.2, 80.1, 76.7, 76.0, 75.7, 74.9, 74.45, 74.40, 73.4, 73.1, 72.9, 42.5, 36.3, 30.7, 16.8. HRMS (ESI): m/z calcd for C₄₅H₅₂O₆Na [M + Na] 711.3656 found 711.3646.

38α :

Colorless syrup; [α]_D²³ = +17.3 (c = 0.7, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.37 – 7.22 (m, 20H), 5.05 (d, J = 11.6 Hz, 1H), 4.99 (d, J = 10.9 Hz, 1H), 4.84 (d, J = 11.6 Hz, 1H), 4.74 (d, J = 11.3 Hz, 2H), 4.69 (d, J = 11.3 Hz, 1H), 4.64 (d, J = 7.7 Hz, 1H), 4.60 (d, J = 11.5 Hz, 1H), 4.56 (d, J = 11.2 Hz, 1H), 3.85 – 3.77 (m, 2H), 3.75 (d, J = 2.8 Hz, 1H), 3.51 (dd, J = 9.9, 2.8 Hz, 1H), 3.20 (d, J = 8.3 Hz, 1H), 2.05 (br.s, 3H), 1.95 – 1.89 (m, 3H), 1.86 – 1.79 (m, 3H), 1.61 – 1.52 (m, 6H), 0.88 (d, J = 6.4 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.1, 138.9, 138.7, 128.5, 128.45, 128.41, 128.35, 128.30, 128.2, 127.8, 127.6, 127.5, 127.4, 96.6, 83.8, 79.7, 79.3, 75.3, 75.1, 75.0, 74.2, 74.1, 73.8, 73.2, 42.8, 36.3, 30.7, 16.7. HRMS (ESI): m/z calcd for C₄₅H₅₂O₆Na [M + Na] 711.3656 found 711.3647.

Methyl 2,3,4-tri-O-benzyl-6-O-(2,3,4,6-tetra-O-benzyl-7-deoxy-l-glycero-α/β-d-galacto-heptopyranosyl)-α-d-glucopyranoside (39). 39α and 39β were obtained from the reaction of donor 12 (30.0 mg, 44.30 μmol) and acceptor 23 (22.7 mg, 48.80 μmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 1:4); combined yield (24.0 mg, 54%), α:β = 1.1:1.

39β:

Colorless syrup; [α]_D²³ = +55.9 (c = 0.3, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.38 – 7.31 (m, 8H), 7.30 – 7.17 (m, 27H), 5.10 (d, J = 3.7 Hz, 1H), 5.07 (d, J = 11.5 Hz, 1H), 4.93 (d, J = 10.8 Hz, 1H), 4.85 (d, J = 11.8 Hz, 1H), 4.79 (dd, J = 10.9, 5.9 Hz, 2H), 4.73 (d, J = 11.9 Hz, 1H), 4.73 – 4.64 (m, 4H), 4.59 – 4.50 (m, 5H), 4.07 (dd, J = 10.1, 3.6 Hz, 1H), 3.95 (t, J = 9.3 Hz, 1H), 3.94 – 3.83 (m, 2H), 3.82 (d, J = 3.6 Hz, 1H), 3.78 – 3.68 (m, 3H), 3.65 (d, J = 8.2 Hz, 1H), 3.61 (t, J = 9.5 Hz, 1H), 3.40 (dd, J = 9.6, 3.6 Hz, 1H), 3.29 (s, 3H), 0.93 (d, J = 6.3 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.6, 139.0, 138.9, 138.8, 138.5, 138.3, 128.49, 128.45, 128.42, 128.3, 128.2, 128.1, 128.09, 128.06, 127.97, 127.90, 127.7, 127.64, 127.60, 127.4, 127.3, 127.2, 98.0, 97.5, 82.1, 80.3, 79.4, 78.0, 75.8, 75.7, 75.5, 75.3, 75.1, 74.3, 73.4, 73.4, 72.8, 72.3, 70.6, 66.0, 55.0, 16.7. HRMS (ESI): m/z calcd for C₆₃H₆₈O₁₁Na [M + Na] 1023.4653 found 1023.4648.

39α:

Colorless syrup; [α]_D²³ = +9.3 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.36 – 7.16 (m, 33H), 7.13 – 7.06 (m, 2H), 5.04 (d, J = 11.5 Hz, 1H), 4.98 – 4.91 (m, 2H), 4.84 – 4.73 (m, 5H), 4.71 (d, J = 11.7 Hz, 1H), 4.67 – 4.62 (m, 2H), 4.59 – 4.52 (m, 3H), 4.45 (d, J = 11.2 Hz, 1H), 4.35 (d, J = 7.6 Hz, 1H), 4.21 (dd, J = 10.8, 2.0 Hz, 1H), 3.96 (t, J = 9.3 Hz, 1H), 3.89 (dd, J = 9.8, 7.6 Hz, 1H), 3.86 – 3.78 (m, 2H), 3.76 (d, J = 2.7 Hz, 1H), 3.67 (dd, J = 10.8, 5.1 Hz, 1H), 3.54 – 3.43 (m, 3H), 3.27 (s, 3H), 3.22 (d, J = 8.0 Hz, 1H), 0.94 (d, J = 6.4 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.2, 138.9, 138.7, 138.6, 138.5, 138.4, 138.2, 128.5, 128.48, 128.40, 128.37, 128.33, 128.30, 128.2, 128.19, 128.15, 128.0, 127.9, 127.67, 127.61, 127.5, 127.4, 104.3, 98.0, 83.3, 82.0, 79.9, 79.8, 79.4, 78.2, 75.7, 75.2, 74.9, 74.8, 74.3, 74.2, 73.5, 73.4, 73.2, 70.0, 68.6, 55.2, 17.0. HRMS (ESI): m/z calcd for C₆₃H₆₈O₁₁Na [M + Na] 1023.4653 found 1023.4648.

6-O-(2,3,4,6-Tetra-O-benzyl-7-deoxy-l-glycero-α/β-d-galacto-heptopyranosyl)-1,2:3,4-O-diisopropylidene-α-d-galactopyranose (40). 40α and 40β were obtained from the reaction of donor 12 (35.0 mg, 51.70 μmol) and acceptor 24 (14.8 mg, 56.90 μmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 1:4); combined yield (24.7 mg, 60%), α:β = 1.7:1

40β :

Colorless syrup; [α]_D²³ = +28.3 (c = 0.2, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.38 (d, J = 6.9 Hz, 4H), 7.35 – 7.22 (m, 16H), 5.53 (d, J = 5.0 Hz, 1H), 5.15 (d, J = 3.8 Hz, 1H), 5.05 (d, J = 11.4 Hz, 1H), 4.91 (d, J = 11.7 Hz, 1H), 4.79 (d, J = 11.9 Hz, 1H), 4.76 (d, J = 11.7 Hz, 1H), 4.73 – 4.68 (m, 2H), 4.58 (d, J = 4.4 Hz, 1H), 4.56 (d, J = 4.0 Hz, 1H), 4.53 (dd, J = 7.9, 2.4 Hz, 1H), 4.28 (dd, J = 5.1, 2.3 Hz, 1H), 4.16 (dd, J = 7.9, 1.9 Hz, 1H), 4.10 (dd, J = 10.0, 3.7 Hz, 1H), 4.04 (td, J = 6.9, 2.0 Hz, 1H), 3.97 (dd, J = 10.0, 2.7 Hz, 1H), 3.90 – 3.85 (m, 2H), 3.77 – 3.69 (m, 3H), 1.52 (s, 3H), 1.40 (s, 3H), 1.32 (s, 3H), 1.26 (s, 3H), 0.98 (d, J = 6.2 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.5, 139.0, 138.8, 138.7, 128.4, 128.3, 128.2, 128.1, 127.9, 127.8, 127.7, 127.6, 127.56, 127.52, 127.3, 127.2, 109.2, 108.5, 96.4, 96.1, 80.0, 76.4, 76.3, 75.7, 75.6, 75.35, 75.32, 75.2, 74.3, 73.7, 73.2, 72.9, 72.2, 70.9, 70.8, 70.7, 65.4, 65.1, 26.3, 26.1, 25.0, 24.6, 16.8. HRMS (ESI): m/z calcd for C₄₇H₅₆O₁₁Na [M + Na] 819.3714 found 819.3701.

40α:

Colorless syrup; [α]_D²³ = −2.8 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.46 – 7.42 (m, 2H), 7.38 – 7.22 (m, 18H), 5.56 (d, J = 4.9 Hz, 1H), 5.06 (d, J = 11.2 Hz, 1H), 5.03 (d, J = 11.6 Hz, 1H), 4.87 (d, J = 11.7 Hz, 1H), 4.74 (dd, J = 11.6, 2.8 Hz, 3H), 4.61 (d, J = 5.1 Hz, 1H), 4.58 (d, J = 5.1 Hz, 2H), 4.55 (dd, J = 7.9, 2.4 Hz, 1H), 4.45 (d, J = 7.6 Hz, 1H), 4.29 (dd, J = 5.0, 2.4 Hz, 1H), 4.24 – 4.17 (m, 2H), 4.14 – 4.07 (m, 1H), 3.87 (dd, J = 9.8, 7.6 Hz, 1H), 3.82 (dq, J = 8.5, 6.3 Hz, 1H), 3.78 – 3.70 (m, 2H), 3.52 (dd, J = 9.8, 2.7 Hz, 1H), 3.25 (d, J = 8.1 Hz, 1H), 1.49 (s, 3H), 1.40 (s, 3H), 1.30 (s, 3H), 1.29 (s, 3H), 0.90 (d, J = 6.4 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.2, 139.1, 138.7, 138.6, 128.7, 128.5, 128.4, 128.3, 128.29, 128.20, 127.8, 127.7, 127.69, 127.63, 127.5, 127.45, 127.42, 109.3, 108.6, 104.8, 96.4, 83.0, 79.7, 79.2, 79.1, 75.2, 74.7, 74.2, 74.1, 73.8, 73.4, 71.5, 70.8, 70.6, 69.8, 67.6, 26.1, 26.0, 25.1, 24.5, 16.8. HRMS (ESI): m/z calcd for C₄₇H₅₆O₁₁Na [M + Na] 819.3714 found 819.3698.

Methyl 4-O-(2,3,4,6-tetra-O-benzyl-7-deoxy-l-glycero-α/β-d-galacto-heptopyranosyl)-2,3-O-isopropylidene-α-L-rhamnopyranoside (41). 41α and 41β were obtained from the reaction of 12 (30.0 mg, 44.30 μmol) and acceptor 25 (10.6 mg, 48.80 μmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 1:9); combined yield (23.0 mg, 69%), α:β = 1.8:1

41β:

Colorless syrup; [α]_D²³ = +30.5 (c = 0.2, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.37 – 7.35 (m, 2H), 7.34 – 7.22 (m, 18H), 5.20 (d, J = 3.7 Hz, 1H), 5.04 (d, J = 11.2 Hz, 1H), 4.82 – 4.79 (m, 3H), 4.75 – 4.65 (m, 3H), 4.62 – 4.56 (m, 2H), 4.27 (dd, J = 7.2, 5.7 Hz, 1H), 4.09 (dd, J = 10.2, 3.7 Hz, 1H), 3.98 (d, J = 2.1 Hz, 1H), 3.97 – 3.93 (m, 2H), 3.96 – 3.94 (m, 2H), 3.67 (dq, J = 9.9, 6.3 Hz, 1H), 3.36 (dd, J = 9.9, 7.1 Hz, 1H), 3.33 (s, 3H), 1.43 (s, 3H), 1.32 (d, J = 6.3 Hz, 3H), 1.17 (s, 3H), 1.11 (d, J = 6.4 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.7, 139.0, 138.9, 138.7, 128.4, 128.3, 128.29, 128.22, 127.98, 127.94, 127.6, 127.5, 127.45, 127.40, 127.3, 127.2, 109.0, 98.1 (2C), 81.6, 79.8, 75.7, 75.6, 75.4, 74.2, 73.9, 73.7, 73.0, 72.6, 64.5, 54.7, 28.2, 26.4, 17.9, 16.5. HRMS (ESI): m/z calcd for C₄₅H₅₄O₁₀Na [M + Na] 777.3609 found 777.3601.

41α:

Colorless syrup; [α]_D²³ = −4.4 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.40 – 7.37 (m, 2H), 7.36 – 7.23 (m, 18H), 5.07 (d, J = 11.6 Hz, 1H), 4.93 (d, J = 11.2 Hz, 1H), 4.87 (d, J = 7.8 Hz, 1H), 4.85 – 4.81 (m, 2H), 4.76 – 4.68 (m, 3H), 4.63 – 4.55 (m, 2H), 4.23 (t, J = 6.4 Hz, 1H), 4.07 (d, J = 5.8 Hz, 1H), 3.85 – 3.70 (m, 5H), 3.65 (dq, J = 9.7, 6.1 Hz, 1H), 3.55 (dd, J = 9.8, 2.9 Hz, 1H), 3.38 (s, 3H), 3.23 (d, J = 7.9 Hz, 1H), 1.39 (s, 3H), 1.36 (d, J = 6.2 Hz, 3H), 1.29 (s, 3H), 0.95 (d, J = 6.3 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.1, 138.9, 138.7, 128.44, 128.41, 128.3, 128.28, 128.20, 128.0, 127.8, 127.7, 127.6, 127.5, 127.4, 109.3, 102.3, 98.2, 83.3, 79.8, 79.3, 78.7, 78.4, 75.9, 75.1, 74.9, 74.8, 74.2, 73.7, 73.1, 64.5, 54.9, 27.9, 26.3, 18.1, 16.8. HRMS (ESI): m/z calcd for C₄₅H₅₄O₁₀Na [M + Na] 777.3609 found 777.3592.

Methyl 2,3,6-tri-O-benzyl-4-O-(2,3,4,6-Tetra-O-benzyl-7-deoxy-l-glycero-α/β-d-galacto-heptopyranosyl)-α-d-glucopyranoside (42). 42α and 42β were obtained from the reaction of 12 (30.0 mg, 44.30 μmol) and acceptor 26 (22.7 mg, 48.80 μmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 1:4); combined yield (26.0 mg, 59%), α:β = 1:3.9

42β:

Colorless syrup; [α]_D²³ = +28.2 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.33 – 7.15 (m, 35H), 5.70 (d, J = 3.9 Hz, 1H), 5.02 (d, J = 11.4 Hz, 1H), 4.93 (d, J = 11.5 Hz, 1H), 4.82 (d, J = 11.6 Hz, 1H), 4.74 (d, J = 11.5 Hz, 1H), 4.69 – 4.61 (m, 4H), 4.59 – 4.49 (m, 6H), 4.37 (d, J = 12.3 Hz, 1H), 4.05 – 3.99 (m, 2H), 3.91 – 3.86 (m, 1H), 3.82 – 3.76 (m, 3H), 3.75 – 3.65 (m, 2H), 3.60 (dd, J = 10.6, 6.5 Hz, 1H), 3.56 (d, J = 8.2 Hz, 1H), 3.43 (dd, J = 9.6, 3.5 Hz, 1H), 3.36 (s, 1H), 0.93 (d, J = 6.3 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.5, 139.2, 138.7, 138.6, 138.4, 138.2, 128.4, 128.3, 128.29, 128.25, 127.9, 127.8, 127.74, 127.71, 127.6, 127.56, 127.50, 127.4, 127.2, 127.0, 126.9, 97.6, 97.1, 81.9, 80.2, 80.0, 76.0, 75.8, 75.6, 75.4, 74.3, 74.0, 73.5, 73.4, 73.4, 73.1, 72.8, 70.4, 69.6, 55.1, 16.5. HRMS (ESI): m/z calcd for C₆₃H₆₈O₁₁Na [M + Na] 1023.4653 found 1023.4630.

42α:

Colorless syrup; [α]_D²³ = +26.2 (c = 0.5, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.41 – 7.37 (m, 2H), 7.37 – 7.10 (m, 31H), 7.07 – 7.02 (m, 2H), 5.16 (d, J = 11.2 Hz, 1H), 5.09 (d, J = 10.5 Hz, 1H), 4.87 – 4.70 (m, 7H), 4.68 (d, J = 10.6 Hz, 1H), 4.58 (d, J = 12.0 Hz, 1H), 4.54 – 4.49 (m, 3H), 4.38 (d, J = 12.0 Hz, 1H), 4.32 (d, J = 7.7 Hz, 1H), 4.08 (d, J = 12.2 Hz, 1H), 3.94 (t, J = 9.6 Hz, 1H), 3.86 – 3.75 (m, 4H), 3.70 (p, J = 6.6 Hz, 1H), 3.60 (dt, J = 10.2, 2.7 Hz, 1H), 3.55 (dd, J = 10.6, 2.0 Hz, 1H), 3.39 – 3.32 (m, 4H), 3.19 (dd, J = 9.7, 3.7 Hz, 1H), 3.07 (d, J = 7.8 Hz, 1H), 1.01 (d, J = 6.4 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 140.2, 139.4, 139.0, 138.68, 138.62, 138.1, 129.0, 128.48, 128.40, 128.29, 128.25, 128.1, 128.0, 127.99, 127.93, 127.7, 127.67, 127.62, 127.5, 127.48, 127.42, 127.1, 126.7, 102.5, 98.7, 83.4, 80.5, 80.26, 80.21, 78.9, 75.9, 75.7, 75.2, 74.7, 74.6, 73.9, 73.5, 73.3, 73.2, 70.3, 68.1, 55.3, 17.7. HRMS (ESI): m/z calcd for C₆₃H₆₈O₁₁Na [M + Na] 1023.4653 found 1023.4633.

3-O-(2,3,4,6-Tetra-O-benzyl-7-deoxy-l-glycero-α/β-d-galacto-heptopyranosyl)-1,2:5,6-di-O-isopropylidene-α-d-glucofuranose (43). 43α and 43β were obtained from the reaction of 12 (60.0 mg, 88.60 μmol) and acceptor 27 (25.4 mg, 97.60 μmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 1:4); combined yield (44.0 mg, 61%), α:β = 1:10.2

43β:

Colorless syrup; [α]_D²³ = +14.0 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.39 – 7.19 (m, 20H), 5.83 (d, J = 3.6 Hz, 1H), 5.19 (d, J = 3.7 Hz, 1H), 5.08 (d, J = 11.4 Hz, 1H), 4.91 (d, J = 3.6 Hz, 1H), 4.88 (d, J = 11.7 Hz, 1H), 4.78 – 4.72 (m, 3H), 4.71 – 4.66 (m, 1H), 4.55 (dd, J = 11.8, 5.7 Hz, 2H), 4.47 (q, J = 6.3 Hz, 1H), 4.19 (dd, J = 6.8, 2.8 Hz, 1H), 4.15 (d, J = 2.8 Hz, 1H), 4.11 – 4.04 (m, 2H), 4.01 (dd, J = 8.5, 5.3 Hz, 1H), 3.88 – 3.83 (m, 2H), 3.76 (dq, J = 8.2, 6.3 Hz, 1H), 3.61 (d, J = 8.3 Hz, 1H), 1.41 (s, 3H), 1.40 (s, 3H), 1.21 (s, 3H), 1.02 – 0.91 (m, 6H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.2, 138.76, 138.71, 138.6, 128.49, 128.40, 128.29, 128.25, 128.1, 127.7, 127.68, 127.61, 127.5, 127.3, 111.6, 108.8, 105.3, 99.5, 82.9, 82.8, 81.0, 79.5, 76.1, 75.6, 75.5, 74.4, 73.6, 73.2, 73.0, 72.8, 66.7, 26.9, 26.8, 26.0, 25.3, 16.7. HRMS (ESI): m/z calcd for C₄₇H₅₆O₁₁Na [M + Na] 819. 3714 found 819.3712.

43α:

Colorless syrup; [α]_D²³ = −14.8 (c = 0.3, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.37 – 7.26 (m, 20H), 5.73 (d, J = 3.7 Hz, 1H), 5.06 (d, J = 11.6 Hz, 1H), 4.83 – 4.68 (m, 5H), 4.61 (d, J = 11.6 Hz, 1H), 4.57 (d, J = 11.6 Hz, 1H), 4.51 (d, J = 3.8 Hz, 1H), 4.43 (dd, J = 6.8, 4.1 Hz, 2H), 4.35 (d, J = 3.2 Hz, 1H), 4.30 (dd, J = 5.1, 3.1 Hz, 1H), 4.11 – 4.02 (m, 2H), 3.85 – 3.74 (m, 3H), 3.52 (dd, J = 9.7, 2.8 Hz, 1H), 3.24 (d, J = 8.1 Hz, 1H), 1.46 (s, 3H), 1.34 (s, 3H), 1.30 (s, 3H), 1.20 (s, 3H), 0.93 (d, J = 6.3 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.0, 138.6, 138.5, 138.3, 128.55, 128.50, 128.3, 128.04, 128.01, 127.8, 127.74, 127.70, 127.6, 127.5, 111.7, 108.6, 105.2, 101.7, 83.3, 82.7, 80.3, 80.1, 80.0, 79.3, 75.3, 74.5, 74.3, 74.2, 73.6, 73.3, 66.0, 26.7, 26.6, 26.1, 25.4, 16.9. HRMS (ESI): m/z calcd for C₄₇H₅₆O₁₁Na [M + Na] 819. 3714 found 819.3704.

Isopropyl 2,3,4,6-tetra-O-benzyl-7-deoxy-l-glycero-α-d-gluco-heptopyranoside (44). 44α was obtained from the reaction of 17 (35.0 mg, 51.70 μmol) and acceptor isopropyl alcohol (4.4 μL, 56.10 μmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 3:97); yield (17.2 mg, 57%), only α.

44α:

Colorless syrup; [α]²⁰_D = +15.7 (c = 0.2, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.42 – 7.19 (m, 18H), 7.13 (d, J = 7.2 Hz, 2H), 4.96 (d, J = 10.8 Hz, 1H), 4.92 (d, J = 10.8 Hz, 1H), 4.82 (d, J = 10.9 Hz, 1H), 4.76 – 4.63 (m, 3H), 4.39 (m, 3H), 4.06 – 3.93 (m, 2H), 3.83 (t, J = 9.2 Hz, 1H), 3.62 (t, J = 9.1 Hz, 1H), 3.46 (t, J = 8.5 Hz, 1H), 3.19 – 3.10 (m, 1H), 1.32 (d, J = 6.4 Hz, 3H), 1.30 (d, J = 6.1 Hz, 3H), 1.23 (d, J = 6.2 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 138.8, 138.73, 138.72, 128.44, 128.41, 128.3, 128.0, 127.9, 127.7, 127.65, 127.61, 127.5, 102.9, 85.4, 82.4, 78.0, 77.7, 75.7, 74.8, 74.7, 72.5, 71.4, 70.5, 23.8, 22.3, 15.6; HRMS (ESI): m/z calcd for C₃₈H₄₄O₆Na [M+Na]⁺ 619.3030 found 619.3007.

Adamantyl 2,3,4,6-tetra-O-benzyl-7-deoxy-l-glycero-α-d-gluco-heptopyranoside (45). 45α was obtained from the reaction of 17 (35.0 mg, 51.70 μmol) and 1-adamantanol (8.6 mg, 56.10 μmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 5:95); yield (19.8 mg, 56%), only α.

45α:

Colorless syrup; [α]²⁰_D = +13.6 (c = 0.8, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.40 – 7.18 (m, 18H), 7.14 (dd, J = 8.8, 7.3 Hz, 2H), 5.00 (d, J = 11.0 Hz, 1H), 4.90 (d, J = 10.8 Hz, 1H), 4.81 (d, J = 10.9 Hz, 1H), 4.75 – 4.64 (m, 3H), 4.60 (d, J = 7.8 Hz, 1H), 4.42 – 4.33 (m, 2H), 3.96 (tt, J = 6.4, 3.2 Hz, 1H), 3.82 (t, J = 9.3 Hz, 1H), 3.62 (dd, J = 12.2, 6.0 Hz, 1H), 3.49 – 3.41 (m, 1H), 3.13 (dd, J = 9.6, 2.0 Hz, 1H), 2.14 (s, 3H), 1.92 (d, J = 11.3 Hz, 3H), 1.80 (d, J = 11.4 Hz, 3H), 1.68 – 1.58 (m, 6H), 1.30 (t, J = 6.5 Hz, 3H); ¹³C{¹H} NMR (151 MHz, CDCl₃) δ 138.73, 138.71, 138.69, 138.66, 134.5, 133.7, 130.2, 129.8, 129.0, 128.5, 128.35, 128.31, 128.27, 128.25, 128.24, 128.0, 127.95, 127.56, 127.54, 127.4, 96.8, 85.6, 82.2, 77.9, 77.7, 75.7, 74.9, 74.9, 74.6, 71.2, 70.4, 45.3, 45.3, 42.9, 42.8, 36.3, 36.1, 30.7, 30.7, 30.7, 15.9; HRMS (ESI): m/z calcd for C₄₅H₅₂O₆Na [M+Na]⁺ 711.3656 found 711.3642.

Methyl 2,3,4-tri-O-benzyl-6-O-(2,3,4,6-tetra-O-benzyl-7-deoxy-l-glycero-α/β-d-gluco-heptopyranosyl)-α-d-glucopyranoside (46). 46α and 46β were obtained from the reaction of donor 17 (35.0 mg, 51.70 μmol) and acceptor 23 (26.0 mg, 56.93 μmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 1:9); combined yield (25.0 mg, 49%), α:β = 23.6:1.

46β:

Colorless syrup; [α]²⁰_D =+6.0 (c = 0.1, CHCl₃); ¹H NMR (900 MHz, CDCl₃) δ 7.71 – 6.93 (m, 35H), 5.04 (d, J = 3.5 Hz, 1H), 4.98 (d, J = 10.8 Hz, 1H), 4.95 (dd, J = 10.9, 7.0 Hz, 2H), 4.87 (d, J = 11.1 Hz, 1H), 4.83 (d, J = 10.8 Hz, 1H), 4.76 (d, J = 10.6 Hz, 1H), 4.73 (d, J = 12.0 Hz, 1H), 4.70 – 4.63 (m, 4H), 4.60 (d, J = 12.0 Hz, 1H), 4.57 (d, J = 3.6 Hz, 1H), 4.33 (dd, J = 11.5, 5.7 Hz, 2H), 4.01 (t, J = 9.3 Hz, 1H), 3.97 (t, J = 9.3 Hz, 1H), 3.92 (q, J = 6.9 Hz, 1H), 3.83 – 3.77 (m, 2H), 3.77 – 3.73 (m, 1H), 3.71 – 3.65 (m, 2H), 3.58 (dd, J = 9.6, 3.5 Hz, 1H), 3.54 (dd, J = 9.8, 1.7 Hz, 1H), 3.47 (dd, J = 9.5, 3.5 Hz, 1H), 3.37 (s, 3H), 1.23 (d, J = 6.4 Hz, 3H); ¹³C{¹H} NMR (226 MHz, CDCl₃) δ 138.8, 138.79, 138.6, 138.5, 138.4, 138.3, 128.5, 128.45, 128.43, 128.41, 128.37, 128.33, 128.27, 128.21, 128.1, 128.02, 128.01, 128.0, 127.9, 127.8, 127.7, 127.66, 127.63, 127.61, 127.59, 127.57, 127.4, 127.3, 97.9, 97.0, 82.2, 80.2, 79.9, 77.8, 77.6, 77.2, 75.7, 75.6, 75.0, 74.6, 73.4, 73.4, 72.3, 71.2, 70.8, 70.3, 65.8, 55.1, 14.1; HRMS (ESI): m/z calcd for C₆₃H₇₂O₁₁N [M+NH₄]⁺; 1018.5073; found: 1018.5068.

46α:

Colorless syrup; [α]²⁰_D = +25.3 (c = 0.4, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.71 – 6.93 (m, 35H), 4.97 (ddd, J = 10.1, 7.3, 2.0 Hz, 2H), 4.90 (dd, J = 10.8, 2.0 Hz, 1H), 4.83 – 4.60 (m, 8H), 4.58 (t, J = 2.8 Hz, 1H), 4.51 (dd, J = 11.2, 2.0 Hz, 1H), 4.41 (dd, J = 10.9, 2.0 Hz, 1H), 4.35 (dd, J = 12.0, 2.0 Hz, 1H), 4.28 (dd, J = 7.8, 2.0 Hz, 1H), 4.18 (dd, J = 10.8, 2.3 Hz, 1H), 3.98 (td, J = 9.1, 2.2 Hz, 2H), 3.90 – 3.79 (m, 2H), 3.66 – 3.57 (m, 2H), 3.50 (ddd, J = 9.3, 6.2, 2.9 Hz, 2H), 3.47 – 3.40 (m, 1H), 3.30 (d, J = 1.9 Hz, 3H), 3.11 (d, J = 9.5 Hz, 1H), 1.31 (dd, J = 6.5 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 138.8, 138.6, 138.5, 138.4, 138.1, 128.4, 128.3, 128.2, 128.1, 127.9, 127.8, 127.6, 127.6, 127.5, 127.49, 127.41, 104.6, 97.9, 85.2, 82.1, 82.0, 79.9, 78.2, 77.8, 77.6, 75.7, 75.6, 74.8, 74.8, 74.7, 73.3, 71.5, 70.3, 70.0, 68.9, 55.2, 15.4; HRMS (ESI): m/z calcd for C₆₃H₆₈O₁₁Na [M+Na]⁺ 1023.4653 found 1023.4614.

Methyl 4-O-(2,3,4,6-tetra-O-benzyl-7-deoxy-l-glycero-α/β-d-gluco-heptopyranosyl)-2,3-O-isopropylidene-α-L-rhamnopyranoside (47). 47α and 47β were obtained from the reaction of 17 (80.0 mg, 0.12 mmol) and acceptor 25 (28.3 mg, 0.13 mmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 7:93); combined yield (57.4 mg, 63%), α:β = 7.9:1.

47β:

Colorless syrup; [α]²⁰_D = +7.4 (c = 0.1, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.71 – 7.06 (m, 20H), 5.11 (d, J = 3.4 Hz, 1H), 4.96 (d, J = 10.6 Hz, 1H), 4.90 – 4.73 (m, 4H), 4.68 (dd, J = 11.7, 4.4 Hz, 2H), 4.39–4.33 (m, 2H), 4.17 – 4.06 (t, J = 6.5 Hz, 1H), 4.11–4.10 (d, J = 6.02 Hz, 1H), 4.05 – 3.98 (m, 2H), 3.85–3.79 (m, 2H), 3.74–3.69 (m, 1H), 3.61–3.59 (dd, J = 9.88, 3.42 Hz, 1H), 3.36 (s, 3H), 3.30 (dd, J = 10.0, 6.6 Hz, 1H), 1.48 (s, 3H), 1.39 (d, J = 6.4 Hz, 3H), 1.35 (d, J = 6.3 Hz, 3H), 1.29 (s, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 138.7, 138.7, 138.5, 138.2, 129.7, 128.5, 128.4, 128.2, 128.17, 128.15, 127.8, 127.65, 127.61, 127.5, 109.1, 98.5, 98.2, 83.1, 82.2, 80.5, 78.1, 77.4, 75.7, 74.9, 74.1, 73.9, 71.8, 70.7, 64.6, 54.8, 28.1, 26.2, 17.9, 15.7; HRMS (ESI): m/z calcd for C₄₅H₅₄O₁₀Na [M+Na]⁺ 777.3609 found 777.3598.

47α:

Colorless syrup; [α]²⁰_D = +13.5 (c = l.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 8.09 – 6.21 (m, 20H), 4.92 (dd, J = 11.0, 6.0 Hz, 2H), 4.88 – 4.80 (m, 3H), 4.74 (d, J = 10.9 Hz, 1H), 4.69–4.63 (m, 2H), 4.47 (d, J = 10.9 Hz, 1H), 4.40 (d, J = 11.9 Hz, 1H), 4.21 (t, J = 6.0 Hz, 1H), 4.09 (d, J = 5.7 Hz, 1H), 4.00 (dd, J = 6.3, 2.1 Hz, 1H), 3.84 (t, J = 9.3 Hz, 1H), 3.71 – 3.60 (m, 3H), 3.42 (t, J = 8.5 Hz, 1H), 3.38 (s, 3H), 3.17 (dd, J = 9.7, 2.1 Hz, 1H), 1.49 (s, 3H), 1.36 (d, J = 4.9 Hz, 3H), 1.33–1.32 (m, 6H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 138.9, 138.8, 138.7, 128.4, 128.4, 128.37, 128.32, 127.9, 127.7, 127.68, 127.64, 127.62, 127.57, 127.50, 109.4, 102.4, 98.1, 85.3, 82.4, 79.0, 78.4, 77.9, 77.7, 76.0, 75.6, 74.8, 74.7, 71.4, 70.1, 64.3, 54.9, 28.1, 26.3, 18.1, 15.7; HRMS (ESI): m/z calcd for C₄₅H₅₄O₁₀Na [M+Na]⁺ 777.3609; found: 777.3585.

Methyl 2,3,6-tri-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-7-deoxy-l-glycero-α/β-d-gluco-heptopyranosyl)-α-d-glucopyranoside (48). 48α and 48β were obtained from the reaction of 17 (80.0 mg, 0.12 mmol) and acceptor 26 (60.0 mg, 0.13 mmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 1:9); combined yield (71.0 mg, 59%), α:β = 7.7:1.

48β:

Colorless syrup; [α]²⁰_D = +30.0 (c = 0.1, CHCl₃); ¹H NMR (600 MHz, CDCl₃) δ 7.98 – 6.79 (m, 35H), 5.70 (d, J = 3.5 Hz, 1H), 5.00 (d, J = 11.6 Hz, 1H), 4.92 – 4.83 (m, 2H), 4.80 (dd, J = 11.9, 8.9 Hz, 1H), 4.73 (d, J = 10.6 Hz, 1H), 4.68 (d, J = 12.1 Hz, 1H), 4.63 – 4.59 (m, 2H), 4.59 – 4.53 (m, 3H), 4.51 – 4.45 (m, 2H), 4.37–4.32 (m, 2H), 4.06 (dd, J = 9.6, 8.4 Hz, 1H), 3.90 (dd, J = 9.9, 8.4 Hz, 1H), 3.88 – 3.82 (m, 2H), 3.81 – 3.71 (m, 2H), 3.69 (dd, J = 10.7, 2.3 Hz, 1H), 3.58 (ddd, J = 8.1, 6.0, 3.5 Hz, 2H), 3.54 (dd, J = 9.8, 1.9 Hz, 1H), 3.51 (dd, J = 9.9, 3.5 Hz, 1H), 3.38 (s, 3H), 1.19 (d, J = 6.4 Hz, 3H); ¹³C{¹H} NMR (151 MHz, CDCl₃) δ 139.0, 138.9, 138.6, 138.3, 138.1, 138.0, 137.9, 128.4, 128.38, 128.34, 128.30, 128.26, 128.21, 128.19, 128.12, 128.0, 127.9, 127.7, 127.65, 127.64, 127.57, 127.50, 126.8, 97.8, 96.2, 82.3, 82.1, 80.2, 79.7, 77.8, 75.6, 74.7, 74.3, 74.1, 73.4, 73.4, 73.2, 72.4, 71.4, 70.6, 69.6, 69.1, 55.1, 15.2,; HRMS (ESI): m/z calcd for C₆₃H₆₈O₁₁Na [M+Na]⁺ 1023.4653 found 1023.4615.

48α:

Colorless syrup; [α]²⁰_D = +23.0 (c = 0.2, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.44 – 7.38 (m, 2H), 7.34 – 7.21 (m, 28H), 7.20 – 7.15 (m, 2H), 7.14 – 7.06 (m, 3H), 5.19 (d, J = 11.4 Hz, 1H), 4.88 (d, J = 10.8 Hz, 1H), 4.85 – 4.71 (m, 6H), 4.65 (d, J = 12.0 Hz, 1H), 4.61 (m, 2H), 4.58–4.56 (m, 2H), 4.49 (d, J = 11.1 Hz, 1H), 4.41 (d, J = 12.1 Hz, 1H), 4.34 (d, J = 7.8 Hz, 1H), 4.03 – 3.90 (m, 2H), 3.86 (q, J = 9.5 Hz, 3H), 3.58 (d, J = 10.0 Hz, 1H), 3.52 – 3.45 (m, 3H), 3.40 (t, J = 8.5 Hz, 1H), 3.35 (s, 3H), 3.02 (dd, J = 9.7, 2.1 Hz, 1H), 1.30 (d, J = 6.3 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.8, 138.9, 138.8, 138.7, 138.6, 138.0, 128.6, 128.5, 128.49, 128.41, 128.38, 128.32, 128.2, 128.1, 128.0, 127.91, 127.88, 127.75, 127.6, 127.5, 127.35, 127.31, 127.0, 102.9, 98.6, 85.4, 83.0, 80.9, 79.0, 77.9, 77.8, 75.7, 75.7, 74.9, 74.7, 73.8, 73.5, 72.1, 70.3, 69.9, 67.9, 55.4, 15.3; HRMS (ESI): m/z calcd for C₆₃H₇₂O₁₁N [M+NH₄]⁺ 1018.5100; found: 1018.5063.

3-O-(2,3,4,6-Tetra-O-benzyl-7-deoxy-l-glycero-α/β-d-gluco-heptopyranosyl)-1,2:5,6-di-O-isopropylidene-α-d-glucofuranose (49). 49α and 49β were obtained from the reaction of 17 (40.0 mg, 59.10 μmol) and acceptor 27 (16.9 mg, 65.00 μmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 1:9); combined yield (30.0 mg, 63%), α:β = 1.7:1.

49β:

Colorless syrup; [α]²²_D = +40.9 (c = 0.5, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.35 – 7.22 (m, 18H), 7.16 – 7.12 (m, 2H), 5.87 (d, J = 3.7 Hz, 1H), 5.39 (d, J = 3.5 Hz, 1H), 4.96 (d, J = 10.8 Hz, 1H), 4.84 (d, J = 10.6 Hz, 1H), 4.79 – 4.74 (m, 2H), 4.71 – 4.64 (m, 2H), 4.58 (d, J = 3.7 Hz, 1H), 4.46 (ddd, J = 8.6, 6.1, 4.5 Hz, 1H), 4.36 (d, J = 11.6 Hz, 1H), 4.30 (d, J = 10.7 Hz, 1H), 4.25 (d, J = 2.8 Hz, 1H), 4.09 (dd, J = 8.5, 2.8 Hz, 1H), 4.06 – 3.99 (m, 3H), 3.95 (t, J = 9.4 Hz, 1H), 3.78 (t, J = 9.4 Hz, 1H), 3.60 (dd, J = 9.8, 3.6 Hz, 1H), 3.54 (dd, J = 9.8, 1.4 Hz, 1H), 1.48 (s, 3H), 1.42 – 1.34 (m, 6H), 1.27 (s, 3H), 1.24 (s, 3H). ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 138.6, 138.3, 138.1, 128.56, 128.50, 128.1, 128.0, 127.9, 127.89, 127.84, 127.80, 127.7, 127.6, 111.8, 109.2, 105.2, 97.5, 84.2, 81.9, 81.4, 79.9, 79.6, 77.7, 75.7, 75.2, 74.5, 73.0, 72.3, 71.1, 70.9, 67.3, 27.1, 26.8, 26.2, 25.6, 15.7. HRMS (ESI): m/z calcd for C₄₇H₅₆O₁₁Na [M + Na] 819. 3714 found 819.3724.

49α:

Colorless syrup; [α]²²_D = +6.7 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.34 – 7.21 (m, 18H), 7.17 (dd, J = 7.8, 1.8 Hz, 2H), 5.76 (d, J = 3.7 Hz, 1H), 4.90 (d, J = 10.9 Hz, 1H), 4.85 – 4.76 (m, 2H), 4.73 (s, 2H), 4.65 (d, J = 11.7 Hz, 1H), 4.52 – 4.44 (m, 3H), 4.43 – 4.34 (m, 3H), 4.27 (d, J = 3.0 Hz, 1H), 4.12 – 4.03 (m, 2H), 4.01 (qd, J = 6.4, 2.0 Hz, 1H), 3.85 (t, J = 9.3 Hz, 1H), 3.64 (t, J = 9.1 Hz, 1H), 3.40 (dd, J = 9.2, 7.8 Hz, 1H), 3.17 (dd, J = 9.6, 2.1 Hz, 1H), 1.48 (s, 3H), 1.42 (s, 3H), 1.34 (d, J = 6.5 Hz, 3H), 1.29 (s, 3H), 1.23 (s, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 138.7, 138.5, 138.4, 138.3, 128.5, 128.49, 128.40, 127.89, 127.86, 127.80, 127.77, 127.73, 127.70, 127.6, 127.5, 111.9, 108.5, 105.2, 102.2, 85.1, 82.9, 82.2, 80.8, 80.4, 78.1, 77.5, 75.7, 75.0, 74.9, 73.5, 71.4, 70.1, 65.9, 26.7, 26.7, 26.1, 25.2, 15.3. HRMS (ESI): m/z calcd for C₄₇H₅₆O₁₁Na [M + Na] 819. 3714 found 819.3729.

Isopropyl 2,3,4,6-tetra-O-benzyl-7-deoxy-d-glycero-α/β-d-gluco-heptopyranoside (50). 50α and 50β were obtained from the reaction of donor 19 (35.0 mg, 51.70 μmol) and acceptor isopropyl alcohol (4.4 μL, 56.10 μmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 3:97); combined yield (18.5 mg, 61%), α:β = 1.2:1.

50β:

Colorless syrup; [α]²⁰_D = +38.4 (c = 0.1, CHCl₃); ¹H NMR (600 MHz, CDCl₃) δ 7.82 – 6.79 (m, 20H), 5.02 (d, J = 10.8 Hz, 1H), 4.89 (d, J = 3.6 Hz, 1H), 4.80 (d, J = 10.7 Hz, 1H), 4.75 (d, J = 12.0 Hz, 1H), 4.66 (d, J = 11.3 Hz, 2H), 4.59 – 4.51 (m, 3H), 4.07 – 4.00 (m, 2H), 3.96 (dd, J = 8.8, 3.9 Hz, 1H), 3.78 (d, J = 6.7 Hz, 1H), 3.53 – 3.46 (m, 1H), 3.35 – 3.29 (m, 1H), 1.27 (dd, J = 6.3, 1.7 Hz, 3H), 1.17 (dd, J = 6.2, 1.7 Hz, 3H), 1.07 (dd, J = 6.6, 1.8 Hz, 3H); ¹³C{¹H} NMR (151 MHz, CDCl₃) δ 138.9, 138.7, 138.3, 138.0, 128.45, 128.42, 128.38, 128.3, 128.2, 128.14, 128.12, 128.0, 127.9, 127.8, 127.64, 127.60, 127.5, 127.4, 94.2, 82.5, 80.3, 78.6, 76.8, 75.8, 74.8, 73.1, 73.0, 72.1, 70.9, 70.6, 69.5, 68.5, 23.3, 21.0, 13.9; HRMS (ESI): m/z calcd for C₃₈H₄₄O₆Na [M+Na]⁺ 619.3030 found 619.3011.

50α:

Colorless syrup; [α]²⁰_D = +6.9 (c = 0.l, CHCl₃); ¹H NMR (600 MHz, CDCl₃) δ 7.66 – 7.17 (m, 18H), 7.17 (dd, J = 6.7, 2.9 Hz, 2H), 5.00 (d, J = 10.8 Hz, 1H), 4.96 (d, J = 10.9 Hz, 1H), 4.84 (d, J = 10.9 Hz, 1H), 4.79 (d, J = 10.9 Hz, 1H), 4.72 (d, J = 10.9 Hz, 1H), 4.62 – 4.56 (m, 2H), 4.48 (d, J = 7.8 Hz, 1H), 4.06–4.02 (m, 2H), 3.84 (qd, J = 6.6, 1.5 Hz, 1H), 3.67 (t, J = 9.0 Hz, 1H), 3.54 (dd, J = 9.9, 1.5 Hz, 1H), 3.42 (ddd, J = 9.9, 8.2, 3.4 Hz, 2H), 1.34 (d, J = 6.2 Hz, 3H), 1.27 (d, J = 6.1 Hz, 3H), 1.16 (d, J = 6.6 Hz, 3H); ¹³C{¹H} NMR (151 MHz, CDCl₃) δ 138.9, 138.6, 138.5, 138.0, 128.5, 128.4, 128.39, 128.31, 128.27, 128.21, 128.1, 127.9, 127.8, 127.7, 127.6, 127.5, 127.4, 102.4, 85.3, 82.5, 78.1, 76.8, 76.0, 75.7, 74.8, 74.6, 73.6, 72.6, 70.6, 29.7, 23.9, 22.4, 14.4; ESI-HRMS: m/z calc for C₃₈H₄₄O₆Na [M+Na]⁺; 619.3030; found: 619.3009.

Adamantyl 2,3,4,6-tetra-O-benzyl-7-deoxy-d-glycero-α/β-d-gluco-heptopyranoside (51). 51α and 51β were obtained from the reaction of donor 19 (35.0 mg, 51.70 μmol) and 1-adamantanol (8.6 mg, 56.10 μmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 5:95) as colorless syrup; combined yield (18.2 mg, 52%), α:β = 1.1:1.

51 α/β:

¹H NMR (600 MHz, CDCl₃) δ 7.99 – 6.88 (m, 40H), 5.31 (d, J = 3.7 Hz, 1H), 5.04 (dd, J = 10.9, 4.5 Hz, 2H), 4.95 (d, J = 10.8 Hz, 1H), 4.88–4.79 (m, 4H), 4.72 (dd, J = 9.6, 6.7 Hz, 5H), 4.64 – 4.54 (m, 6H), 4.23 (dd, J = 10.4, 1.5 Hz, 1H), 4.09 (t, J = 9.2 Hz, 1H), 3.82 (qt, J = 7.3, 3.5 Hz, 2H), 3.68 (t, J = 8.9 Hz, 1H), 3.55 (dd, J = 10.1, 1.7 Hz, 1H), 3.49 (dd, J = 9.7, 3.7 Hz, 1H), 3.46 – 3.33 (m, 3H), 2.17–2.13 (m, 8H), 1.97–1.92 (m, 7H), 1.89 – 1.81 (m, 8H), 1.68 – 1.59 (m, 12H), 1.16 (d, J = 6.6 Hz, 3H), 1.13 (d, J = 6.6 Hz, 3H); ¹³C{¹H} NMR (151 MHz, CDCl₃) δ 139.0, 138.9, 138.7, 138.6, 138.3, 138.1, 128.4, 128.39, 128.36, 128.24, 128.22, 128.14, 128.06, 128.0, 127.94, 127.90, 127.75, 127.72, 127.58, 127.54, 127.51, 127.4, 127.3, 127.28, 127.25, 96.5, 89.5, 85.7, 82.5, 82.4, 80.5, 78.9, 78.3, 77.2, 75.7, 75.6, 75.6, 74.8, 74.8, 74.6, 74.5, 73.7, 72.7, 70.7, 70.5, 70.5, 42.8, 42.5, 36.3, 36.3, 30.7, 30.7, 29.7, 22.7, 14.4, 14.3; HRMS (ESI): m/z calcd for C₄₅H₅₂O₆Na [M+Na]⁺; 711.3656; found: 711.3621.

Methyl 2,3,4-tri-O-benzyl-6-O-(2,3,4,6-tetra-O-benzyl-7-deoxy-d-glycero-α/β-d-gluco-heptopyranosyl)-α-d-glucopyranoside (52). 52α and 52β were obtained from the reaction of donor 19 (35.0 mg, 51.70 μmol) and acceptor 23 (26.0 mg, 56.10 μmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 1:9); combined yield (45.0 mg, 60%), α:β = 1.1:1

52β:

Colorless syrup; [α]²⁰_D = +6.0 (c = 0.7, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 8.48 – 6.58 (m, 35H), 4.99 (d, J = 3.5 Hz, 1H), 4.94 (dd, J = 10.9, 2.0 Hz, 2H), 4.89 (d, J = 11.0 Hz, 1H), 4.84 (d, J = 11.1, 1H), 4.80 (d, J = 10.9 Hz, 1H), 4.75 (d, J = 10.8 Hz, 1H), 4.70 – 4.58 (m, 4H), 4.57 – 4.46 (m, 4H), 4.42 (d, J = 12.2 Hz, 1H), 4.03 – 3.92 (m, 3H), 3.85 (dd, J = 11.6, 4.7 Hz, 1H), 3.78–3.73 (m, 3H), 3.62 (t, J = 9.4 Hz, 1H), 3.51 – 3.44 (m, 1H), 3.41 – 3.38 (m, 1H), 3.34 (s, 3H), 3.32 – 3.25 (m, 1H), 1.05 (d, J = 6.5 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.0, 138.8, 138.7, 138.6, 138.55, 138.53, 138.3, 128.5, 128.46, 128.43, 128.3, 128.2, 128.1, 128.0, 127.9, 127.7, 127.6, 127.5, 98.0, 96.8, 82.2, 80.4, 80.3, 78.3, 78.0, 75.8, 75.2, 74.6, 73.5, 73.3, 72.2, 71.0, 70.6, 70.5, 65.8, 55.2, 14.1; HRMS (ESI): m/z calcd for C₆₃H₆₈O₁₁Na [M+Na]⁺ 1023.4653 found 1023.4622.

52α:

Colorless syrup; [α]²⁰_D = −1.6 (c = 0.7, CHCl₃); ¹H NMR (600 MHz, CDCl₃) δ 7.67 – 6.28 (m, 35H), 4.99 (dd, J = 11.0, 5.7 Hz, 2H), 4.94 (d, J = 10.8 Hz, 1H), 4.89 – 4.76 (m, 5H), 4.73 – 4.63 (m, 3H), 4.58 (d, J = 9.1 Hz, 2H), 4.51 (d, J = 11.1 Hz, 1H), 4.34 (d, J = 7.7 Hz, 1H), 4.25 (dd, J = 10.6, 1.6 Hz, 1H), 4.01 (t, J = 9.3 Hz, 1H), 3.86 – 3.81 (m, 2H), 3.75 – 3.65 (m, 2H), 3.63 – 3.45 (m, 4H), 3.43 (d, J = 9.2 Hz, 1H), 3.36 (s, 3H), 1.15 (d, J = 6.6 Hz, 3H); ¹³C{¹H} NMR (151 MHz, CDCl₃) δ 138.9, 138.8, 138.5, 138.4, 138.3, 138.1, 137.9, 128.5, 128.4, 128.38, 128.36, 128.33, 128.24, 128.20, 128.1, 128.08, 128.03, 128.01, 127.96, 127.92, 127.89, 127.85, 127.78, 127.75, 127.6, 127.5, 127.4, 103.8, 98.1, 85.3, 82.2, 82.0, 79.7, 78.1, 77.9, 76.3, 75.8, 75.7, 74.9, 74.9, 74.6, 73.7, 73.4, 70.7, 69.8, 68.3, 55.2, 53.4, 53.2, 53.0, 52.9, 52.7, 14.5; HRMS (ESI): m/z calcd for C₆₃H₆₈O₁₁Na [M+Na]⁺ 1023.4653 found 1023.4620.

General procedure for VT ¹H NMR experiment.

A solution of 9, 12, 17 or 19 (20.0 mg, 0.03 mmol) in CD₂Cl₂ (0.7 mL) containing TTBP (7.3 mg, 0.03 mmol) was placed into an NMR tube and cooled to −80 °C in the NMR probe. The first ¹H spectrum was obtained, then the sample was quickly removed from the probe and addition of Tf₂O (9.9 μL, 0.06 mmol) precooled at −78 °C was done quickly. The sample was returned to the NMR probe and ¹H spectrum was recorded after 10 mins. The temperature was increased by 10 °C increments every 10 minutes and ¹H NMR spectra were acquired at each temperature.

1-O-(2,3,4,6-tetra-O-benzyl-7-deoxy-d-glycero-α/β-d-galacto-heptopyranosyl)-2,3,4,6-tetra-O-benzyl-7-deoxy-d-glycero-β-d-galacto-heptopyranoside (56 & 57). These compounds were obtained from the decomposition of donor 9 when variable temperature NMR studies were carried out following the general procedure for VT study. The reaction mixture was quenched with triethylamine (20 μL) at rt and diluted with dichloromethane (5 mL), washed with saturated NaHCO₃ (2 mL). The organic layer was separated and dried over Na₂SO₄, filtered, and concentrated under reduced pressure. Purification by flash column chromatography on silica gel (4:1, hexane /ethyl acetate) afforded the desired product as a colorless syrup (7.0 mg, 43%) in a 1:1.5 ratio of α:β anomers.

56β:

Colorless syrup; [α]_D²³ = +29.5 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.35 – 7.15 (m, 40H), 5.26 (d, J = 3.5 Hz, 2H), 4.97 (d, J = 11.2 Hz, 2H), 4.75 (s, 8H), 4.53 (d, J = 11.4 Hz, 2H), 4.46 (d, J = 11.2 Hz, 2H), 4.23 (d, J = 2.6 Hz, 2H), 4.19 (d, J = 11.4 Hz, 2H), 4.14 (dd, J = 10.1, 3.5 Hz, 2H), 4.06 (dd, J = 10.1, 2.6 Hz, 2H), 3.89 – 3.78 (m, 4H), 1.21 (d, J = 5.6 Hz, 6H). ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.2, 138.96, 138.90, 138.6, 128.3, 128.2, 128.0, 127.7, 127.5, 127.49, 127.43, 127.3, 92.3, 79.5, 75.7, 74.7, 73.8, 73.6, 72.8, 72.6, 70.2, 16.2. HRMS (ESI): m/z calcd for C₇₀H₇₄O₁₁Na [M + Na] 1113.5123 found 1113.5115.

57α:

Colorless syrup; [α]_D²³ = +4.9 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.36 – 7.13 (m, 40H), 5.24 (d, J = 3.0 Hz, 1H), 5.05 – 4.94 (m, 3H), 4.77 (d, J = 11.8 Hz, 1H), 4.76 – 4.66 (m, 5H), 4.67 – 4.57 (m, 2H), 4.56–4.47 (m, 4H), 4.25 – 4.13 (m, 3H), 4.12 (d, J = 2.9 Hz, 1H), 4.07 (dd, J = 6.3, 2.7 Hz, 2H), 3.93 – 3.77 (m, 4H), 3.52 (dd, J = 9.8, 2.8 Hz, 1H), 3.13 (d, J = 8.8 Hz, 1H), 1.31 (d, J = 6.0 Hz, 3H), 1.25 (d, J = 5.7 Hz, 6H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 139.3, 139.2, 139.1, 138.9, 138.8, 138.7, 138.4, 128.5, 128.4, 128.3, 128.25, 128.20, 128.0, 127.86, 127.81, 127.7, 127.6, 127.56, 127.52, 127.4, 127.28, 127.25, 102.5, 98.6, 82.6, 80.0, 79.4, 78.2, 76.3, 74.88, 74.82, 74.5, 74.3, 73.5, 73.3, 72.9, 70.6, 70.3, 16.9, 16.3. HRMS (ESI): m/z calcd for C₇₀H₇₄O₁₁Na [M + Na] 1113.5123 found 1113.5083.

1,6-Anhydro-2,3,4-tri-O-benzyl-7-deoxy-l-glycero-α-d-galacto-heptopyranose (59). This compound was obtained from the decomposition of donor 12 when variable temperature NMR studies were carried out following the general procedure for VT study. The reaction mixture was quenched with triethylamine (20.0 μL) at rt and diluted with dichloromethane (5 mL), washed with saturated NaHCO₃ (2 mL). The organic layer was separated and dried over Na₂SO₄, filtered, and concentrated under reduced pressure. Purification by flash column chromatography on silica gel (9:1, hexane /ethyl acetate) afforded the decomposed product 59 (7.1 mg, 53%) as colorless syrup.

[α]_D²³ = −32.1 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.36 – 7.26 (m, 13H), 7.25 – 7.22 (m, 2H), 5.36 (t, J = 1.6 Hz, 1H), 4.82 (q, J = 6.5 Hz, 1H), 4.61 (d, J = 12.1 Hz, 1H), 4.57 (s, 2H), 4.51 (d, J = 12.0 Hz, 1H), 4.45 (d, J = 12.3 Hz, 1H), 4.37 (d, J = 12.3 Hz, 1H), 3.98 (dd, J = 3.8, 1.4 Hz, 1H), 3.84 (dd, J = 5.2, 3.8 Hz, 1H), 3.79 (dt, J = 5.2, 1.5 Hz, 1H), 3.47 (t, J = 1.9 Hz, 1H), 1.15 (d, J = 6.4 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 138.4, 138.2, 137.7, 128.5, 128.4, 128.1, 128.0, 127.9, 127.7, 100.8, 77.9, 76.6, 74.3, 73.5, 73.1, 72.1, 71.3, 71.2, 21.3. HRMS (ESI): m/z calcd for C₂₈H₃₀O₅Na [M + Na] 469.1985 found 469.1985.

1,6-Anhydro-2,3,4-tri-O-benzyl-7-deoxy-l-glycero-α-d-gluco-heptopyranose (61). This compound was obtained from the decomposition of donor 17 when variable temperature NMR studies were carried out following the general procedure for VT study. The reaction mixture was quenched with triethylamine (20 μL) at rt and diluted with dichloromethane (5 mL), washed with saturated NaHCO₃ (2 mL). The organic layer was separated and dried over Na₂SO₄, filtered, and concentrated under reduced pressure. Purification by flash column chromatography on silica gel (9:1, hexane /ethyl acetate) afforded the decomposed product 61 (4.3 mg, 43%) as colorless syrup. [α]²⁰_D = −20.4 (c = 0.21, CHCl₃). ¹H NMR (600 MHz, CDCl₃) δ 7.36 – 7.24 (m, 15H), 5.47 (s, 1H), 4.61 (d, J = 12.5 Hz, 1H), 4.53 – 4.38 (m, 3H), 4.18 (qd, J = 6.2, 1.0 Hz, 1H), 4.14 – 4.10 (m, 1H), 3.60 (dq, J = 2.7, 1.3 Hz, 1H), 3.39 – 3.34 (m, 1H), 3.32 – 3.28 (m, 1H), 1.16 (d, J = 6.3 Hz, 3H); ¹³C{¹H} NMR (151 MHz, CDCl₃) δ 138.0, 137.9, 137.9, 128.5, 128.43, 128.41, 128.0, 127.9, 127.9, 127.7, 101.2, 79.7, 76.5, 72.7, 72.2, 71.7, 71.2, 29.7, 21.0; HRMS (ESI): m/z calcd for C₂₈H₃₀O₅Na [M+Na]⁺ 469.1985 found 469.1964.

1,6-Anhydro-2,3,4-tri-O-benzyl-7-deoxy-d-glycero-α-d-gluco-heptopyranose (63). This compound was obtained from the decomposition of donor 19 when variable temperature NMR studies were carried out following the general procedure for VT study. The reaction mixture was quenched with triethylamine (20.0 μL) at rt and diluted with dichloromethane (5 mL), washed with saturated NaHCO₃ (2 mL). The organic layer was separated and dried over Na₂SO₄, filtered, and concentrated under reduced pressure. Purification by flash column chromatography on silica gel (9:1, hexane /ethyl acetate) afforded the decomposed product 63 (8.0 mg, 29%) as colorless syrup. [α]²²_D = −11.4 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.36 – 7.27 (m, 15H), 5.37 (s, 1H), 4.69 – 4.56 (m, 6H), 4.34 (d, J = 4.3 Hz, 1H), 3.98 (qd, J = 6.5, 4.1 Hz, 1H), 3.70 (t, J = 4.7 Hz, 1H), 3.60 (d, J = 4.9 Hz, 1H), 3.35 (d, J = 4.5 Hz, 1H), 1.21 (d, J = 6.6 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 138.3, 138.0, 137.9, 128.5, 128.4, 128.0, 127.97, 127.92, 127.7, 101.3, 81.1, 79.9, 78.8, 75.0, 73.5, 73.2, 71.9, 71.7, 14.7. HRMS (ESI): m/z calcd for C₂₈H₃₀O₅Na [M+Na]⁺; 469.1985; found: 469.1988.

p-Methylphenyl 6-O-acetyl-2,3,4,-tri-O-benzyl-7-deoxy-1-thio-l-glycero-α-d-gluco-heptopyranoside (66). Acetic anhydride (0.11 mL, 1.16 mmol) was added to a stirred solution of 14 (0.33 g, 0.58 mmol) and 4-dimethylaminopyridine (7.0 mg, 0.06 mmol) in anhydrous pyridine (2.5 mL) at 0 °C. After complete addition it was shifted to room temperature and stirred for 2 hours. It was quenched with ice cold 1N HCl solution (5 mL) and diluted with Ethyl acetate (10 mL). The organic layer was washed with saturated NaHCO₃ solution (5 mL). The organic layer was dried over Na₂SO₄, filtered and concentrated, purified by silica gel chromatography (1:4, EtOAc/Hexane) to give 66 (0.32 g, 90%) as a white solid. m. p.: 130–134 °C, [α]²²_{D =} – 13.5 (c = 1.0, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.53 – 7.46 (m, 2H), 7.44 – 7.40 (m, 2H), 7.37 – 7.25 (m, 13H), 7.11 (d, J = 7.9 Hz, 2H), 5.30 (qd, J = 6.5, 1.8 Hz, 1H), 4.98 – 4.91 (m, 2H), 4.85 (d, J = 10.8 Hz, 1H), 4.82 (d, J = 10.0 Hz, 1H), 4.75 (d, J = 10.2 Hz, 1H), 4.57 (d, J = 9.7 Hz, 1H), 4.43 (d, J = 10.0 Hz, 1H), 3.70 (t, J = 8.9 Hz, 1H), 3.55 (t, J = 9.4 Hz, 1H), 3.50 (t, J = 9.3 Hz, 1H), 3.23 (dd, J = 9.7, 1.8 Hz, 1H), 2.34 (s, 3H), 2.10 (s, 3H), 1.34 (d, J = 6.5 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 170.5, 138.3, 138.08, 138.04, 137.6, 133.0, 129.7, 128.6, 128.5, 128.4, 128.3, 128.1, 128.0, 127.8, 88.2, 87.0, 81.0, 80.3, 75.9, 75.5, 75.3, 67.7, 21.4, 21.2, 16.5; HRMS (ESI): m/z calcd for C₃₇H₄₀O₆SNa [M + Na] 635.2437 found 635.2443.

p-Methylphenyl 6-O-acetyl-2,3,4-tri-O-benzyl-7-deoxy-1-thio-l-glycero-α-d-gluco-heptopyranosyl sulfoxide (67). It was obtained following the general protocol B for sulfoxide as white solid (0.17 g, 83%) in a 1:1.6 ratio of two unidentified isomer.

Mixture of (R) and (S) sulfoxides: ¹H NMR (500 MHz, CDCl₃) δ 7.55 (d, J = 7.9 Hz, 5.8H), 7.41 (d, J = 6.9 Hz, 2H), 7.38 – 7.18 (m, 48H), 5.23 (qd, J = 6.7, 1.7 Hz, 1.6H), 5.11 (qd, J = 6.5, 1.9 Hz, 1H), 5.06 (d, J = 10.3 Hz, 1H), 5.02 – 4.94 (m, 2H), 4.92 (d, J = 11.2 Hz, 1H), 4.89 – 4.76 (m, 8H), 4.72 (d, J = 10.2 Hz, 1.6H), 4.44 – 4.41 (m, 1.7H), 4.41 – 4.35 (m, 2.3H), 4.13 (t, J = 9.4 Hz, 1H), 3.86 (d, J = 9.8 Hz, 1H), 3.84 – 3.76 (m, 4.5H), 3.60 (t, J = 9.3 Hz, 1H), 3.48 – 3.41 (m, 1.6H), 3.37 (dd, J = 9.8, 1.7 Hz, 1.6H), 2.99 (dd, J = 9.7, 2.0 Hz, 1H), 2.40 (s, 3H), 2.38 (s, 5.1H), 2.06 (s, 3H), 2.00 (s, 5.1H), 1.24 (d, J = 6.5 Hz, 5.4H), 0.75 (d, J = 6.5 Hz, 3H).¹³C{¹H} NMR (151 MHz, CDCl₃) δ 170.5, 170.2, 141.8, 141.5, 138.2, 137.9, 137.6, 137.4, 137.1, 136.0, 129.6, 129.4, 128.66, 128.63, 128.5, 128.47, 128.45, 128.3, 128.2, 128.1, 128.0, 127.96, 127.93, 127.90, 127.6, 126.1, 125.3, 95.0, 93.8, 86.9, 86.0, 81.4, 79.8, 77.3, 77.1, 76.9, 76.7, 75.9, 75.7, 75.4, 75.2, 74.9, 74.1, 67.6, 67.3, 21.5, 21.4, 21.2, 16.4, 15.4; HRMS (ESI): m/z calcd for C₃₇H₄₀O₇SNa [M + Na] 651.2387 found 651.2386.

Adamantyl 6-O-acetyl-2,3,4-tri-O-benzyl-7-deoxy-l-glycero-α/β-d-gluco-heptopyranoside (68). 68α and 68β were obtained from the reaction of 67 (33.0 mg, 52.50 μmol) and 1-adamantanol (8.8 mg, 57.70 μmol) following the general procedure for glycosylation (Ethyl acetate/hexane, 1:9); combined yield (21.0 mg, 61%), α:β = 1:1.94.

68β:

Colorless syrup; [α]²²_D = +22.5 (c = 0.9, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.37 – 7.26 (m, 15H), 5.39 (qd, J = 6.6, 1.5 Hz, 1H), 5.36 (d, J = 3.6 Hz, 1H), 5.00 (d, J = 10.6 Hz, 1H), 4.85 (d, J = 9.8 Hz, 1H), 4.81 (d, J = 10.6 Hz, 1H), 4.69 (d, J = 2.0 Hz, 2H), 4.40 (d, J = 9.9 Hz, 1H), 4.04 (t, J = 9.3 Hz, 1H), 3.84 (dd, J = 10.0, 1.6 Hz, 1H), 3.52 (dd, J = 9.7, 3.6 Hz, 1H), 3.42 (dd, J = 10.0, 8.8 Hz, 1H), 2.23 – 2.10 (m, 3H), 2.07 (s, 3H), 1.88 – 1.74 (m, 6H), 1.68 – 1.51 (m, 8H), 1.29 (d, J = 6.4 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 170.5, 138.8, 138.2, 137.9, 128.6, 128.56, 128.53, 128.2, 128.1, 128.0, 127.98, 127.93, 127.7, 89.8, 82.0, 80.0, 78.1, 76.9, 75.7, 75.5, 74.8, 73.0, 71.8, 68.1, 42.9, 42.7, 36.3, 30.7, 21.3, 17.1. HRMS (ESI): m/z calcd for C₄₀H₄₈O₇Na [M + Na] 663.3292 found 663.3278.

68α:

Colorless syrup; [α]²²_D = +2.9 (c = 0.7, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.36 – 7.33 (m, 2H), 7.32 – 7.22 (m, 13H), 5.27 (qd, J = 6.5, 2.0 Hz, 1H), 5.01 (d, J = 11.0 Hz, 1H), 4.93 (d, J = 10.9 Hz, 1H), 4.79 (d, J = 10.1 Hz, 1H), 4.76 (d, J = 10.9 Hz, 1H), 4.72 (d, J = 11.0 Hz, 1H), 4.63 (d, J = 7.8 Hz, 1H), 4.37 (d, J = 10.2 Hz, 1H), 3.64 (t, J = 9.0 Hz, 1H), 3.54 (t, J = 9.3 Hz, 1H), 3.44 (dd, J = 9.2, 7.8 Hz, 1H), 3.19 (dd, J = 9.7, 2.0 Hz, 1H), 2.16 (p, J = 3.0 Hz, 3H), 2.04 (s, 3H), 1.95 – 1.88 (m, 3H), 1.80 (dq, J = 11.4, 2.6 Hz, 3H), 1.68 – 1.57 (m, 6H), 1.53 (s, 2H), 1.32 (d, J = 6.3 Hz, 3H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 170.7, 138.6, 138.5, 137.8, 128.5, 128.49, 128.46, 128.3, 128.0, 127.9, 127.7, 96.7, 85.3, 82.2, 77.4, 76.3, 75.8, 75.3, 75.2, 75.0, 67.5, 42.9, 36.3, 30.7, 21.4, 16.7. HRMS (ESI): m/z calcd for C₄₀H₄₈O₇Na [M + Na] 663.3292 found 663.3290.