Structural Bias Effect On Azidation at C‑1 and C‑2 of Alkyl-3,6-anhydro‑d‑hexofuranosides: Synthetic Approach to Natural Products and Derivatives

Abstract

3,6-Anhydro hexofuranose sugars are the structural motif of natural product furanodictines A–B and sauropunols A–D, F, and H. Conversion of the 2-hydroxyl group of alkyl-3,6-anhydro-5-O-benzoyl-d-glucofuranosides to triflate intermediates followed by azidation reaction yielded 2-deoxy-2-azido derivatives when the substituents at C-1and C-2 are in cis relation; on the other hand, in the case of trans substituents, the products were α-glycosyl azide analogues. A similar reaction of butyl-3,6-anhydro-5-O-benzoyl- d-mannofuranosides, obtained from the corresponding α- or β-d-glucofuranoside through appropriate oxidation and reduction reactions, yielded only 2-deoxy-2-azido products. We report here in a synthetic approach to 2-substituted sauropunols, furanodictines A–B, and related analogues, along with 1,4-disubstituted 1,2,3-triazolyl glycoconjugates and N-glycosyl amide starting from d-glucose derived precursors.

Introduction

Glycosyl and nonglycosyl azidosugars are versatile precursors in organic and bioorganic chemistry. The glycosyl azides are the pioneers of various triazolyl glycoconjugates, , N-glycosides, , and glycosyl ureas. , They are also used as anomeric protecting groups as well as useful glycosyl donors. , 1,4-Disubstituted 1,2,3-triazolyl glycoconjugates, derived from glycosyl azides of structurally diverse carbohydrates, emerged as promising anti-inflammatory, antidiabetic, anticancer, antitubercular, antileishmanial, antimalarial, antimicrobial and insecticide, antifungal and antibacterial, and antiviral HIV-1 agents, whereas various N-glycosyl amides involved in several cell recognition processes including immune response, inflammation, tumor proliferation, and metastasis. Besides, nonglycosyl azides are mainly used for the synthesis of natural/unnatural nitrogen heterocycles and aminosugars, , which are also utilized as living cell probes in activity-based proteomic profiling to metabolic labeling. Recent study demonstrated that they hamper glycan acceptance by carbohydrate processing enzymes. The different carbohydrate moieties present in various classes of bioactive molecules are important for their properties. Recently, 3,6-anhydro-d-hexofuranose-based natural products sauropunols (A–D, F and H) (1–6), 7, , 8 , and furanodictines (A–B) (9–10) ,,, were isolated from different natural sources (Figure ). Medicinal plant-generated 1–4 are noncytotoxic and possess anti-inflammatory activities, and for 2, it is comparable to the drug indomethacin. Compounds 3/4 have strong inhibition activities on TGF-β1-induced lung fibroblast differentiation, while 5 and 8 have low toxicity. Amino sugars 9 and 10 together approve neuritis creation in the presence of nerve growth factor, but 10 increases neuritis formation in vitro in rat pheochromocytoma PC-12 cells.

1.

Natural 3,6-anhydro-d-hexofuranose analogues (1–10).

Inspired by the biochemical properties of sauropunols, Xie et al. reported several nitrate derivatives of sauropunols A–B, including 11–14, which have potent nitric oxide (NO) liberating ability and vasodilatory capacity, and among them, 11 has greater vasorelaxation activities than the drug isosorbide dinitrate. They also reported synthesis of 7 and its several O-glycosyl analogues which emerged as anti-inflammatory agents. Synthetic azido nucleoside 15 exhibited exciting therapeutic efficacy in controlling cancer cells without any untoward effects on normal host cells, and it also reduces the tumor trouble and survives in cells to a greater extent than the anticancer drug 5-fluorouracil, whereas, triazolyl glycoconjugate 16, based on l-glucurono-3,6-lactone core, shows potent anticancer activity (Figure ).

2.

3,6-Anhydro-d-hexofuranose core containing bioactive compounds (11–16).

Even with important biological properties, very little attention has been paid to the synthetic analogues of these natural products. Also, the competent synthesis of furanodictines A–B continues unabated as their previous preparation involved either multisteps or costly starting materials. ,,, The above studies indicate that syntheses of 2-substituted sauropunols, 1,2,3-triazole-linked glycoconjugates and N-glycosyl amide using 3,6-anhydro-d-hexofuranose moiety would be an appropriate goal for new molecules to meet the demand for chiral drug molecules as well. Toward the objective, we thought to introduce azido group at C-1 and C-2 of the methyl/ethyl/butyl-3,6-anhydro-5-O-benzoyl-d-glucofuranosides (17a–e) (Schemes , , and ) using their structural bias to obtain α-glycosyl and nonglycosyl azides, respectively. The initiation generated a new strategy for obtaining literally scarce but biochemically important , α-glycosyl azides in comparison to previous reports starting from 1,6-anhydro sugars, glycosyl halides, or thioglycosyl ester. , The glycosyl azides could be exploited to prepare 1,4-disubstituted α-1,2,3-triazolyl glyconjugates and N-glycosyl amide. It was conceivable that the nonglycosyl azides could potentially be used to generate corresponding 2-azido and 2-acetamido sauropunols (A–D, F, and H), furanodictines (A–B), and other related analogues using a strategy previously reported from 18 , (Scheme ) to generate 19 (mixture of anomers).

2. Synthesis of 2-β-Azido Sauropunol A (25) and Its Analogue (24), 2-β-Acetamido Sauropunol A (27) and Its Analogue (26), and 2-β-Azido Sauropunol C/D (28)­ .

^a Reagents and conditions: (i) (a) Tf₂O, Py, DCM, 0 °C, 3 h; (b) NaN_3, DMF, 80 °C, 8 h; (ii) (a) PPh₃, THF-MeCN (1:1), rt, 2 h; (b) Ac₂O, Py, 12 h; (iii) K₂CO₃, MeOH, 2 h; (iv) 4% H₂SO₄ in 3:1 MeCN-H₂O, rt, 48 h.

4. Synthesis of Glycosyl Azides (41–43) Based on 3,6-Anhydro-d-hexofuranose .

^a Reagents and conditions: (i) (a) Tf₂O, Py, DCM, 0 °C, 2 h; (b) NaN_3, DMF, (90–100)°C, (10–17) h; (ii) K₂CO₃, MeOH, 2 h.

7. Synthesis of 2-β-Hydroxy- (55), 2-α-Azido- (58), 2-α-Acetamido­(59)-Sauropunol B, and Furanodictine A (9) and Its β-Anomeric Butylglycoside (60) Analogue .

^a Reagents and conditions: (i) (a) Phl­(OAc)₂, TEMPO, DCM, rt, 12 h; (b) NaBH₄, THF, rt, 15 min; (ii) K₂CO₃, MeOH, 2 h; (iii) (a) Tf₂O, Py, DCM, 0 °C, 3 h; (b) NaN₃, DMF, 80 °C, 8h; (iv) (a) PPh₃, THF-MeCN (1:1), rt, 2h; (b) Ac₂O, Py, 12 h; (v) isovaleryl chloride, Et₃N, DCM, rt, 10 h; (vi) 4% H₂SO₄ in 3:1 MeCN-H₂O, rt, 40 h.

8. Synthesis of 2-α-Azido Sauropunol A (66)­ .

^a Reagents and conditions: (i) (a) Phl­(OAc)₂, TEMPO, DCM, rt, 12 h; (b) NaBH₄, THF, rt, 15 min; (ii) (a) Tf₂O, Py, DCM, 0 °C, 3 h; (b) NaN₃, DMF, 80 °C, 5h; (iii) k₂CO₃, MeOH, 2 h.

1. Previous Reports of Azidation at C-2 of Anomeric Mixture of 18 .

Results and Discussion

Synthesis of 2-β-Azido Sauropunols (A, C/D), 2-β-Acetamido Sauropunol A, and Their Analogues

The substrates 17a–b were separately treated with triflic anhydride in the presence of pyridine at low temperature, and the respective triflate intermediates were then directly heated with NaN₃in DMF to furnish 20–21 (79–85)% (Scheme ), which upon PPh₃-mediated reduction in THF-MeCN and subsequent acetylation yielded the corresponding acetamido products 22 (78%) and 23 (inseparable from Ph₃PO). Debenzoylation reaction of 20–21 and 22–23 by treatment with K₂CO₃ in MeOH smoothly furnished 2-β-azido sauropunol A (25) (94%) and its analogue (24) (91%), 2-β-acetamido sauropunol A (27) (71% in two stems), and its analogue (26) (92%). Hydrolysis of 24 by using 4% H₂SO₄ in 3:1 MeCN-H₂O produced 2-β-azido sauropunol C/D (28) (85%) as a mixture of anomers. Regarding structure of the compounds, the presence of azido functionality in 20–21 was confirmed by the appearance of the peak atν_max (2099–2113) cm^–1 in their IR spectra, and their structures were established from the X-ray structure analysis of the representative molecule 21 (Figure S1, Supporting Information). The absence of benzoyl protons signals in 24–27, appearance of a sharp singlet of methyl protons of the acetamido group at δ (1.85–1.99) in 26–27, and the absence of methyl protons signals in 28, in the ¹H NMR spectra, confirmed their formation.

Synthesis of Furanodictine B and Its Analogue

Further, as the structural core of 22–23 and 26–27 are very close to furanodictine B, we used this opportunity for its synthesis along with its analogues. For this, the compounds 26–27 were esterified separately with isovaleryl chloride and Et₃N to obtain the desired glycoside analogues (29–30) (Scheme ) with (91–94)% yield. Selective acid-catalyzed hydrolysis of glycoside bonds of 29 and 22 using 4% H₂SO₄ in 3:1 MeCN-H₂O produced furanodictine B (10) (84%) and its 5-O-benzoate analogue (31) (82%), respectively. The NMR spectra of 10 was consistent with the literature, while the formation of 31 was obvious from disappearance of proton signals of the aglycon methyl group in its ¹H NMR spectrum.

3. Synthesis of Furanodictine B (10) and Its Glycosides (29–30) and Benzoate (31) Analogue .

^a Reagents and conditions: (i) isovaleryl chloride, Et₃N, DCM, rt, 10 h; (ii) 4% H₂SO₄ in 3:1 MeCN-H₂O, rt, 40 h.

Installation of Azide Functionality at C-1: Synthesis of Triazolyl and Acetomidyl Glycoconjugates

Next, an attempt was made to prepare the intermediate 38a (Scheme ) of 2-β-azido sauropunol H via the azidation reactions of β-anomers as in Scheme . For this, treatment of methyl 3,6-anhydro-5-O-benzoyl-β-d-glucofuranoside (17c) with triflic anhydride and pyridine at low temperature, and after workup, subsequent reaction of the triflate intermediate 32 with NaN₃ led to an unexpected glycosyl azide 38 (71%) with migration of glycosyl methoxy group to C-2. In the similar reaction condition, β-anomers 17d–e were also produced the glycosyl azides 39–40 (26–57)%. Debenzoylation reaction of 38–40 smoothly produced the desired products 41–43 with (89–93)% yields. In the azidation reaction of 32–34, the required temperature and time were the least for 32 (with higher yield) and the most for 34 (with lower yield). From the above observation, it was concluded that the azidation reaction went through exclusively formed oxirane ion intermediates 35–37, which were nucleophilic attacked by the N₃ ^–at more reactive C-1 center from the least hindered side (exo face) to yield 38–40. The other side (endo face) was blocked by cis-fused 5,5-bicyclic ring with a β-glycosyl alkoxy group, and the product 38a was not formed from 17c. Besides, the oxirane ring was formed in the less available endo face more favorably for less hindered glycosyl methoxy group compared to more hindered glycosyl n-butoxy group, and this also reflected in their respective reaction temperature, time, and yield. Previously, DAST-mediated similar 1,2-migration of anomeric groups (OMe and OBn) in α-l-tallofuranoside system was reported by Kiso et al. to generate α-glycosyl fluoride through concomitant attack of fluoride ion at the C-1 center and migration of alkoxy groups. Our proposed mechanism of azide attack through oxirane ion intermediates (35–37) is also supported by literature reports involving N-, O-, , and S , -linked anomeric group migration and the “stereoelectronic guidelines for the anionic nucleophilic displacement of furanoside”. The azido functionality in 38–40 was confirmed by the presence of a peak at ν_max(2112–2113) cm^–1 in the IR spectra, while the appearance of the C-1 signals was attached to nitrogen atom at δ (93.74–94.95) in their ¹³C NMR spectra. These values are quite low as compared to the C-1 signals (joined to the oxygen atom) at δ (109.82–111.14) of 17c–e. Finally, the absolute structure of 38 was confirmed by subsequent X-ray diffraction analysis of 50 (in Scheme ) (Figure S2, Supporting Information). This analysis also settles the absolute structure of 39 and 40.

6. Synthesis of N-Glycosyl Acetamides on 3,6-Anhydro-d-mannofuranose Core (50 and 52)­ .

^a Reagents and conditions: (i) (a) PPh_3, THF-MeCN (1:1), rt, 2 h; (b) Ac₂O, Py, 12 h; (ii) K₂CO₃, MeOH, 2 h.

Accordingly, utilizing the benefit of the above α-glycosyl azides, we decided to synthesize biochemically important 1,4-disubstituted α-1,2,3-triazolyl glycoconjugates. To pursue, we chose 38, which on treatment with the alkynes 44 and 45 in the presence of CuSO₄ and sodium ascorbate (NaAsc) in t-BuOH-H₂O through click chemistry yielded the respective triazole adducts 46–47 (69–73)% (Scheme ), which on debenzoylation reaction smoothly afforded the desired products 48–49. Appearance of the four proton signals of the phenyl ring in 48, and the proton signals for the n-propyl group in 49 along with a sharp singlet at δ (7.46–8.24) for the C-5 proton of their triazole rings in the ¹H NMR spectra established the success of the reactions.

5. Synthesis of 1,4-Disubstituted Triazolyl Glycoconjugates Based on 3,6-Anhydro-d-mannofuranose (46–49)­ .

^a Reagents and conditions: (i) CusO_4, NaAsc, t-BuOH-H₂O (3:2), rt, 16 h; (ii) K₂CO_3, MeOH, rt, 2 h.

On the other hand, PPh₃ mediated azide reduction of 38 (Scheme ) and subsequent acetylation reaction furnished α-N-glycosyl acetamide 50 (78%), which after debenzoylation reaction using K₂CO₃ in MeOH furnished 52 as anomeric mixture through the possible furanose ring opening imine intermediate 51. The existence of an acetamide group in 50 was evident from the appearance of the sharp singlet of methyl protons at δ 1.92 in the ¹H NMR spectrum. The structural confirmation of 50 was also obtained from single crystal X-ray analysis (Figure S4, Supporting Information).

Synthesis of 2-β-Hydroxy Sauropunol B, 2-α-Azido Sauropunols B, 2-α-Acetamido Sauropunol B, Furanodictine A, and Its Analogues

Then, we utilized the structural disparity of 17e with respect to 17b to synthesize 2-substituted sauropunol B along with furanodictine A and its glycoside analogue. To achieve the target, TEMPO-BAIB-mediated oxidation of 17e afforded the ketone intermediate 53, which on NaBH₄ reduction in THF produced the alcohol 54 (82%, two steps) with inversion of configuration (Scheme ). The hydride ion attacks the ketone functionality at C-2 from the less hindered exo face as the endo face is blocked by the cis-fused 5,5-bicyclic ring with a β-glycosyl n-butoxy substituent. The structural confirmation of 54 was confirmed from single crystal X-ray analysis (Figure S3, Supporting Information). Debenzoylation reaction of 54 produced 2-β-hydroxy sauropunol B (55) (95%). While converting the 2-OH group to OTf of 55, the azide group was introduced by using NaN₃ adopting the same procedure as described in Scheme to prepare 56 (86%), which on selective azide reduction and reaction of 56–57 produced 2-α-azido sauropunol B (58) (95%) and 2-α-acetamido sauropunol B (59) (97%), which treated with isovaleryl chloride and Et₃N in dichloromethane to obtain 60 (95%), the glycoside analogue of furanodictine A. Selective glycoside bonds cleavage of 60 using 4% H₂SO₄ in 3:1 MeCN-H₂O furnished the natural product furanodictine A (9) with 85% yield. ¹H and ¹³CNMR spectra of 9 was consistent with the literature values.

Synthesis of 2-α-Azido Sauropunol A (66)

Finally, an effort was made to prepare 2-α-azido sauropunol A (66) from 17b. For this, 17b was oxidized to obtain the ketone intermediate 61 (Scheme ), which, upon NaBH₄ reduction, produced the alcohols 62 and 17b as an inseparable mixture on silica gel with 84% yield in a 2:1 ratio, as predicted from the ¹H NMR spectrum. The presence of a cis-fused 5,5-bicyclic ring makes the endo face of 61 less accessible to hydride ion compared to the exo face, though the endo face of 61 is more open compared to 53 due to the absence of β-anomeric group in the endo face. As a result, the hydride ion attacks the ketone functionality at C-2 of 61 preferentially from the less hindered exo face to obtain 62 as a major product. However, the mixture of OTf intermediates 63 and 64, obtained from the mixture of 17b and 62, was treated with NaN₃ in DMF to obtain 65 and 21 with 45 and 22% yield, respectively, from 17b. The debenzoylation reaction of 65 smoothly produced the desired product 66 (92%). Interestingly, despite having an antiperiplanar arrangement between C-1 and C-2 substituents, 63 does not undergo the NGP reaction like 32 – 34. The plausible explanation is that in the case of 32–34, the approach of N₃ ^– from the endo face was forbidden as the face was blocked by the β-anomeric alkoxy group with a cis-fused 5,5-bicyclic ring, and that created the possibility of less favorable oxirane ion intermediate formation through the NGP reaction. In case of 63, alone α-anomeric alkoxy group failed to oppose the direct attack of N₃ ^– at C-2 from the exo face, and that ruled out any other possibility of azidation reaction. Similar observation was reported by Yoda et.al, and it is also supported by literature guidelines. The azido functionality at C-2 of 65 was confirmed by the appearance of a peak at ν_max 2110 cm^–1 in the IR spectrum, while a sharp doublet appeared for C-1 proton at δ 5.17 with coupling constant (J) 4.2 Hz ¹H NMR spectra due to the cis-relationship of C-1 and C-2 hydrogen, and existence of C-1 peak at δ 105.12 in ¹³C NMR confirmed the presence of -O ⁿ Bu group at anomeric position.

Conclusions

In conclusion, this work describes a general and efficient strategy for the synthesis of α-glycosyl azides along with 2-azido analogues of alkyl-3,6-anhydro-d-hexofuranosides using the stereochemical bias of the said carbohydrate precursors. One of the glycosyl azides was converted to structurally important 1,4-disubstituted α-1,2,3-triazolyl glycoconjugates and N-glycosyl acetamides. 2-Azido analogues were converted to furanodictine A (26%) and furanodictine B (12%) in 11 and 9 steps, respectively, starting from d-glucose along with their benzoate and glycoside derivatives. These substrates were also utilized for the synthesis of 2-β-azido-, 2-β-acetamido and 2-α-azido-sauropunol A, 2-β-hydroxy-, 2-α-azido- and 2-α-acetamido sauropunol B, and 2-β-azido sauropunol C/D with good yields. Using the structural bias of the above carbohydrate precursors, syntheses of furanodictine B in high yield and 2-fluoro analogue of sauropunols (A–D, F, and H) are in progress in our laboratory for structure activity measurement studies. At last, our strategy for α-glycosyl azide synthesis could be used in other appropriate alkyl glycosides to explore a new dimension of N-glycoside chemistry.

Experimental Section

General Information

For the moisture-sensitive reactions, oven-dried glass-wares were used under N₂ (g). Precoated plates (0.25 mm, Silica Gel 60 F₂₅₄) were used for TLC analysis and visualized by UV light (254 nm) and chemical staining with the Liebermann–Burchard reagent. Melting points were determined in open capillaries and are uncorrected. Specific rotations were measured with an Anton Paar Modular Circular Polarimeter (MCP) 200 using a sodium lamp source (589 nm) and are reported as ${[\alpha ]}_D^{T{}^{°}\mathrm{C}}$ (c = g/100 mL, solvent). Infrared spectroscopy was done in a PerkinElmer FT-IR spectrometer spectrum II. ¹H and ¹³C NMR spectra were recorded using Bruker 300 and 400 MHz spectrometers. For reference, residual solvent signals or internal standards were used. NMR spectra are reported as chemical shifts (δ) in parts per million (ppm) and to show multiplicities, the following abbreviations were used: s = singlet, d = doublet, dd = doublet of doublet, ddd = doublet of doublet of doublet, t = triplet, q = quartet, dt = doublet of triplet, dq = doublet of quartet, hept = heptet, and m = multiplet. Coupling constants (J) are reported in Hz. HRMS (ESI, M/Z) analysis was recorded using an LCQ-ORBITRAP-XL instrument. X-ray diffraction data of compounds 21, 50, and 54 were collected on a Bruker SMART APEX2 area detector. CCDC (2425143–2425145) contains the crystallographic data (Supporting Information S2, S3, and S4) of the compounds and can be obtained at https://summary.ccdc.cam.ac.uk/structure-summary form.

General Procedure 1 (G.P-1) for Triflate Formation and Subsequent Azidation with NaN₃

Suitable starting material (17a–17e, 54, and 62) was dissolved in dry dichloromethane (DCM) along with pyridine (3.5 equiv) and cooled 0 °C. Tf₂O (2 equiv) was slowly added, and the reaction mixture was stirred at 0 °C for 3 h. It was washed with water followed by brine. The organic layer was dried (Na₂SO₄) and evaporated to dryness under vacuum. Residue was dissolved in minimum volume of dry DMF. NaN₃ (15 equiv) was added to the solution heated at (80–100) °C for (8–17) h. The solvent was evaporated, and crude mass was extracted with EtOAc. The organic layer was washed with water, dried (Na₂SO₄), and concentrated. The crude product was purified by column chromatography.

General Procedure 2 (G.P-2) for Staudinger Reduction and Subsequent Acetylation with Ac₂O

Designated starting material (20–21, 38, and 56) was dissolved in THF-MeCN (1:1), and PPh₃ (1.5eq) was added to it. The reaction mixture was stirred at room temperature for 2 h. The solvent was evaporated under vacuum. The residue was dissolved in pyridine and cooled in an ice bath. Ac₂O (3 equiv) was slowly added to the solution and stirred at room temperature for 12h. It was concentrated in vacuum, and residue was then extracted with EtOAc. The organic layer was washed with water, dried (Na₂SO₄), and concentrated. Crude mass was purified by column chromatography to obtain the desired compound.

General Procedure 3 (G.P-3) for Debenzoylation using K₂CO₃/MeOH

To a solution of suitable starting material (20– 23, 38– 40, 46– 47, 50, 54, 56–57, and 65) in methanol was added K₂CO₃ (1.5 equiv) and serried at room temperature for 2 h. It was concentrated, and the residue was extracted with EtOAc. The organic layer was washed with water, dried (Na₂SO₄), and evaporated. The residue was purified by column chromatography to obtain the desired product.

General Procedure 4 (G.P4) for Acid-Catalyzed Glycoside Bond Cleavage

A solution of the required starting material (24, 29–30, and 60) in H₂SO₄ + H₂O + MeCN (1:6:18) was stirred at room temperature for (40–48) h. The reaction mixture was neutralized by portion-wise addition of solid CaCO₃. It was filtered and filtrate was concentrated. The residue was purified by column chromatography to obtain the desired product.

General Procedure 5 (G.P-5) for Esterification with Isovaleryl Chloride/Et₃N

Suitable starting material (26–27, 59) was dissolved in dry DCM along with Et₃N (2.4 equiv) and cooled in an ice bath. Isovaleryl chloride (1.5eq) was added to the reaction mixture and stirred at room temperature for further 10 h. It was diluted with DCM and washed with saturated aqueous NaHCO₃ solution and then water. The organic layer was then dried (Na₂SO₄), concentrated, and purified by column chromatography to obtain the desired isovalerate ester.

Methyl-3,6-anhydro-2-azido-2-deoxy-5-O-benzoyl-α-d-mannofuranoside (20)

20 was prepared from 17a using G.P-1 after heating at 80 °C for 8 h. The crude product was purified by silica gel (100–200 mesh) column chromatography using 7% ethyl acetate (EA) in hexane as an eluent to obtain 20 (85%) as white solid. mp 45–47 °C; ${[\alpha ]}_D^{25}$ = 288.45 (c 0.52, MeOH); IR (KBr): ν_max 2099.12, 1724.50, 1276.61 cm^–1; ¹H NMR (400 MHz, CDCl₃) δ 8.11–8.09 (m, 2H), 7.61–7.57 (m, 1H), 7.48–7.44 (m, 2H), 5.34–5.30 (m, 1H), 4.94–4.91 (m, 2H), 4.84 (t, J = 5.6 Hz, 1H), 4.22 (dd, J = 9.3, 6.4 Hz, 1H), 4.09 (dd, J = 9.3, 7.1 Hz, 1H), 3.88 (dd, J = 6.0, 2.9 Hz, 1H), 3.28 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 166.05, 133.50, 130.01 (2C), 129.56, 128.60 (2C), 108.52, 82.19, 79.46, 73.34, 70.52, 66.80, 56.00; HRMS (ESI, m/z) calcd for C₁₄H₁₅N₃O₅ (M+H) 306.1090, found 306.1096.

Butyl-3,6-anhydro-2-azido-2-deoxy-5-O-benzoyl-α-d-mannofuranoside (21)

21 was prepared from 17b using G.P-1 after heating at 80 °C for 8 h. Crude was purified by silica gel (100–200 mesh) column chromatography using 2% EA in hexane as an eluent to furnish 21 (79%) as a white crystalline solid. m.p. < 30 °C; ${[\alpha ]}_D^{25}$ = 189.91­(c 0.52, MeOH); IR (KBr): ν_max 2110.10, 1726.10, 1273.20 cm^–1; ¹H NMR (400 MHz, DMSO-d ₆) δ 8.01 (d, J = 8.3 Hz, 2H), 7.68 (t, J = 7.4 Hz, 1H), 7.55 (t, J = 7.7 Hz, 2H), 5.34–5.30 (m, 1H), 4.93 (d, J = 4.6 Hz, 1H), 4.89 (t, J = 5.4 Hz, 1H), 4.71 (t, J = 5.5 Hz, 2H), 4.08 (dd, J = 9.8, 5.7 Hz, 1H), 3.99 (dd, J = 9.8, 5.2 Hz, 1H), 3.94 (t-like, J = 6.0, 4.4 Hz, 1H), 3.37 (dt, J = 10.0, 6.6 Hz, 1H), 3.23 (dt, J = 10.1, 6.7 Hz, 1H), 1.38–1.30 (m, 2H), 1.20–1.11 (m, 2H), 0.76 (t, J = 7.4 Hz, 3H); ¹³C NMR (100 MHz, DMSO-d ₆) δ 164.93, 133.50, 129.19 (2C), 129.17, 128.75 (2C), 106.17, 80.69, 78.89, 73.58, 70.29, 68.19, 64.98, 30.92, 18.40, 13.42; HRMS (ESI, m/z) calcd for C₁₇H₂₁N₃O₅ (M+H) 348.1559, found 348.1571.

Methyl-3,6-anhydro-2-acetamido-2-deoxy-5-O-benzoyl-α-d-mannofuranoside (22)

22 was prepared from 20 using G.P-2. The crude product was purified by silica gel (100–200 mesh) column chromatography using 35% EA in hexane as an eluent to obtain 22 (78%) as a white solid. mp (117–118)°C; ${[\alpha ]}_D^{25}$ = 170.40 (c 0.25, MeOH); ¹H NMR (400 MHz, CDCl₃) δ 8.08–8.05 (m, 2H), 7.61–7.57 (m, 1H), 7.48–7.44 (m, 2H), 6.16 (d, J = 5.5 Hz, 1H), 5.41 (m, 1H), 4.95–4.93 (m, 2H), 4.74 (t-like, J = 6.0 Hz, 1H), 4.34–4.29 (m, 1H), 4.20 (m, 1H), 4.08 (dd, J = 9.5, 5.5 Hz, 1H), 3.32 (s, 3H), 2.02 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 170.27, 165.90, 133.61, 129.88 (2C), 129.52, 128.64 (2C), 110.51, 80.80, 80.37, 73.35, 71.36, 56.85, 55.57, 23.40; HRMS (ESI, m/z) calcd for C₁₆H₁₉NO₆Na (M+Na) 344.1110, found 344.1115.

Butyl-3,6-anhydro-2-acetamido-2-deoxy-5-O-benzoyl-α-d-mannofuranoside (23)

23 was prepared from 21 using G.P-2. Purification of crude product by silica gel (100–200 mesh) was unsuccessful to separate 23 from Ph₃PO as pure compound, and it was subjected to next steps without further purification.

Methyl-3,6-anhydro-2-azido-2-deoxy-α-d-annofuranoside (24)

24 was prepared from 20 using G.P-3. Crude mass was purified by neutral alumina (70–230 mesh) column chromatography using 25% EA in hexane as an eluent to produce 24 (91%) as colorless oil. IR (KBr): ν_max 3437.15, 2942.60, 2114.08 cm^–1; ${[\alpha ]}_D^{25}$ = 194.41 (c 0.26, MeOH); ¹H NMR (400 MHz, CD₃OD) δ 4.93 (d, J = 2.4 Hz, 1H), 4.82 (dd, J = 5.9, 4.8 Hz, 1H), 4.55 (t, J = 4.8 Hz, 1H), 4.30–4.24 (m, 1H), 3.98 (dd, J = 8.3, 6.7 Hz, 1H), 3.94 (dd, J = 6.0, 2.4 Hz, 1H), 3.62 (t-like, J = 8.8 Hz, 8.4 Hz, 1H), 3.41 (s, 3H); ¹³C NMR (75 MHz, CD₃OD) δ 108.83, 82.84, 81.41, 72.21, 71.64, 67.88, 54.98; HRMS (ESI, m/z) calcd for C₇H₁₁N₃O₄ (M+Na) 224.0647, found 224.0645.

Butyl-3,6-anhydro-2-azido-2-deoxy-α-d-mannofuranoside (25)

25 was prepared from crude 21 using G.P-3. It was purified by neutral alumina (70–230 mesh) column chromatography using 25% EA in hexane as an eluent to produce 25 (94%) as yellowish oil. IR (KBr): ν_max 3436.50, 2959.47, 2874.20, 2113.42 cm^–1; ${[\alpha ]}_D^{25}$ = 231.56 (c 0.52, MeOH); ¹H NMR (400 MHz, DMSO-d ₆) δ 5.02 (d, J = 6.8 Hz, 1H), 4.99 (d, J = 2.1 Hz, 1H), 4.70 (t, J = 4.2 Hz, 1H), 4.42 (t, J = 4.6 Hz, 1H), 4.16–4.09 (m, 1H), 3.94–3.91 (m, 1H), 3.85 (t, J = 6.4 Hz, 1H), 3.65–3.60 (m, 1H), 3.48–3.39 (m, 2H), 1.53–1.47 (m, 2H), 1.37–1.28 (m, 2H), 0.88 (t, J = 7.4 Hz, 3H); ¹³C NMR (100 MHz, DMSO-d ₆) δ 106.20, 81.29, 80.69, 71.46, 70.80, 67.44, 66.57, 31.06, 18.68, 13.58; HRMS (ESI, m/z) calcd for C₁₀H₁₇N₃O₄ (M+Na) 266.1117, found 266.1118.

Methyl-3,6-anhydro-2-acetamido-2-deoxy-α-d-mannofuranoside (26)

26 was prepared from 22 using G.P-3; 27 has considerable solubility in water. So, to prohibit any loss of compound, MeOH was evaporated completely and the residue was washed with EtOAc carefully and repeatedly to completely extract 26 as crude, which was then purified by neutral alumina (70–230 mesh) column chromatography using isocratic EA as an eluent to produce 26 (92%) as a white solid. m.p = 169–171 C; ${[\alpha ]}_D^{25}$ = 170.40 (c 0.25, MeOH); ¹H NMR (300 MHz, CDCl₃) δ 6.34 (s, 1H), 5.01 (d, J = 1.4 Hz, 1H), 4.79–4.65 (m, 2H), 4.39–4.16 (m, 2H), 3.93 (d, J = 3.9 Hz, 2H), 3.38 (s, 3H); ¹H NMR (400 MHz, CD₃OD) δ 4.91 (d, J = 3.5 Hz, 1H), 4.62–4.57 (m, 2H), 4.29–4.24 (m, 2H), 3.92 (dd, J = 8.7, 6.1 Hz, 1H), 3.63 (dd, J = 8.6, 7.3 Hz, 1H), 3.39 (s, 3H), 1.99 (s, 3H); ¹³C NMR (100 MHz, CD₃OD) δ 172.63, 110.17, 82.39, 80.94, 72.67, 72.32, 58.63, 55.35, 21.84; HRMS (ESI, m/z) calcd for C₉H₁₅NO₅ (M+Na) 240.0848, found 240.0859.

Butyl-3,6-anhydro-2-acetamido-2-deoxy-α-d-mannofuranoside (27)

27 was prepared from 23 using G.P.-3. Crude mass was purified by neutral alumina (70–230 mesh) column chromatography using 40% EA in hexane as an eluent to obtain 27 (71%, from 21 in two steps) as colorless oil. ${[\alpha ]}_D^{25}$ = 122.16 (c 0.50, MeOH); ¹H NMR (400 MHz, DMSO-d ₆) δ 7.81 (d, J = 8.2 Hz, 1H), 4.98 (d, J = 6.3 Hz, 1H), 4.89 (d, J = 4.6 Hz, 1H), 4.46 (t, J = 4.4 Hz, 1H), 4.39 (t-like, J = 5.6, 4.4 Hz, 1H), 4.13–4.07 (m, 2H), 3.79–3.76 (m, 1H), 3.61 (dt, J = 9.9, 6.7 Hz, 1H), 3.44–3.37 (m, 2H), 1.85 (s, 3H), 1.50–1.46 (m, 2H), 1.35–1.26 (m, 2H), 0.87 (t, J = 7.4 Hz, 3H); ¹³C NMR (100 MHz, DMSO-d ₆) δ 169.12, 107.22, 80.92, 79.53, 71.51, 71.07, 67.35, 57.56, 31.17, 22.46, 18.70, 13.64; HRMS (ESI, m/z) calcd for C₁₂H₂₁NO₅ (M+Na) 282.1317, found 282.1324.

3,6-Anhydro-2-azido-2-deoxy-d-mannofuranose (28)

28 was prepared from 24 using G.P4. Reaction was completed in 48 h. Purification of crude product by silica gel (100–200 mesh) column chromatography using 35% EA in hexane as an eluent produced the anomeric mixture 28 as a white semisolid (85%). IR (KBr): ν_max 3413.50, 2117.51 cm^–1.

Minor anomer: ¹H NMR (400 MHz, CDCl₃)­δ 5.42 (d, J = 3.0 Hz, 1H), 4.86 (t-like, J = 5.6, 5.2 Hz, 1H), 4.78 (t, J = 5.3 Hz, 1H), 4.33–4.29 (m, 1H), 4.12–4.05 (m, 1H, merged with another H-signal of major anomer), 3.94–3.92 (m, 1H), 3.73 (dd, J = 9.4, 6.9 Hz, 1H), two −OH signals not discernible; ¹³C NMR (100 MHz, CDCl₃) δ 102.47, 81.95, 81.00, 74.21, 71.76, 67.74.

Major anomer: ¹H NMR (400 MHz, CDCl₃) δ 5.50 (d, J = 4.9 Hz, 1H), 4.74 (t, J = 5.7 Hz, 1H), 4.59 (t-like, J = 5.2, 4.8 Hz, 1H), 4.39–4.35 (m, 1H), 4.12–4.05 (m, 1H, merged with another H-signal of minor anomer), 3.84 (dd, J = 10.2, 5.2 Hz, 1H), 3.68 (t, J = 5.2 Hz, 1H), two −OH signals not discernible; ¹³C NMR (100 MHz, CDCl₃) δ 98.27, 82.99, 82.14, 75.65, 71.62, 62.91. HRMS (ESI, m/z) calcd for C₆H₉N₃O₄ (M-H) 186.0515, found 186.0514.

Methyl-3,6-anhydro-2-acetamido-2-deoxy-5-O-isovaleryl-α-d-mannofuranoside (29)

29 was prepared from 26 using G.P-5. Purification of crude was done by silica gel (100–200 mesh) column chromatography using 40% EA in hexane as an eluent to furnish 29 (94%) as yellow oil; ${[\alpha ]}_D^{25}$ = 139.38 (c 0.26, MeOH); ¹H NMR (400 MHz, CDCl₃) δ 6.14 (d, J = 5.6 Hz, 1H), 5.21–5.16 (m, 1H), 4.91 (d, J = 1.8 Hz, 1H), 4.81 (t, J = 4.8 Hz, 1H), 4.69 (dd, J = 6.5, 5.0 Hz, 1H), 4.28 (td, J = 6.6, 1.8 Hz, 1H), 4.10 (dd, J = 9.3, 5.9 Hz, 1H), 3.89 (dd, J = 9.3, 6.2 Hz, 1H), 3.35 (s, 3H), 2.25 (m, 2H), 2.17–2.08 (m, 1H), 2.03 (s, 3H), 0.97 (d, J = 6.6 Hz, 6H); ¹³C NMR (100 MHz, CDCl₃) δ 172.32, 170.28, 110.57, 80.81, 80.09, 72.52, 70.91, 57.06, 55.40, 43.18, 25.85, 23.35, 22.46, 22.41·; HRMS (ESI, m/z) calcd for C₁₄H₂₃NO₆ (M+Na) 324.1423, found 324.1433.

Butyl-3,6-anhydro-2-acetamido-2-deoxy-5-O-isovaleryl-α-d-mannofuranoside (30)

30 was prepared from 27 using G.P-5. Crude was purified by silica gel (100–200 mesh) column chromatography using 40% EA in hexane as an eluent to yield 30 (91%) as colorless oil. ${[\alpha ]}_D^{25}$ = 139.67 (c 0.51, MeOH); ¹H NMR (400 MHz, DMSO-d ₆) δ 7.92 (d, J = 8.1 Hz, 1H), 5.04–4.99 (m, 1H), 4.86 (d, J = 5.3 Hz, 1H), 4.76 (t, J = 4.8 Hz, 1H), 4.39 (t-like, J = 5.6, 4.8 Hz, 1H), 4.09 (dt, J = 7.7, 5.5 Hz, 1H), 3.91 (dd, J = 9.3, 6.2 Hz, 1H), 3.71 (dd, J = 9.3, 6.2 Hz, 1H), 3.55 (dt, J = 9.5, 6.7 Hz, 1H), 3.39 (dt, J = 9.5, 6.5 Hz, 1H), 2.22 (d, J = 7.1 Hz, 2H), 2.05–1.95 (m, 1H), 1.85 (s, 3H), 1.50–1.43 (m, 2H), 1.33–1.24 (m, 2H), 0.93 (d, J = 6.6 Hz, 6H), 0.85 (t, J = 5.2 Hz, 3H); ¹³C NMR (100 MHz, DMSO-d ₆) δ 171.43, 169.23, 106.67, 79.60, 78.74, 73.33, 69.20, 67.86, 57.07, 42.27, 31.11, 25.15, 22.36, 22.00, 18.60, 13.54; HRMS (ESI, m/z) calcd for C₁₇H₂₉NO₆ (M+Na) 366.1893, found 366.1890.

3,6-Anhydro-2-acetamido-2-deoxy-5-O-benzoyl-d-mannofuranose (31)

31 was prepared from 22 using G.P4. Reaction was completed in 40 h. Crude product was purified by silica gel (100–200 mesh) column chromatography using isocratic EA as an eluent (82%) to furnish anomeric mixture (31) as a white semisolid.

Minor anomer: ¹H NMR (400 MHz, CDCl₃) δ 8.09–8.04 (m, 2H, merged with H signal of major anomer), 7.60–7.56 (m, 1H, merged with H signal of major anomer), 7.47–7.42 (m, 2H, merged with H signal of major anomer), 6.20 (d, J = 7.9 Hz, 1H), 5.40–5.36 (m, 1H, overlapped with H signal of major anomer), 5.27 (d, J = 4.3 Hz, 1H), 5.09 (t, J = 5.0 Hz, 1H), 4.66–4.63 (m, 1H), 4.26–4.22 (m, 1H, partially merged with H signal of major anomer), 4.17 (dd, J = 9.6, 5.9 Hz, 1H), 3.99 (dd, J = 9.6, 5.8 Hz, 1H), 2.04 (s, 3H), −OH signal not discernible;¹³C NMR (75 MHz, CDCl₃) δ171.26, 170.41 (merged with C signal of major anomer), 133.61, 129.93 (2C), 129.48 (merged with C signal of major anomer), 128.64 (2C, merged with C signal of major anomer), 103.81, 80.54, 80.11, 73.76, 71.05, 59.25, 22.82.

Major anomer: ¹H NMR (400 MHz, CDCl₃) δ 8.09–8.06 (m, 2H, merged with H signal of minor anomer), 7.60–7.56 (m, 1H, merged with H signal of minor anomer), 7.47–7.42 (m, 2H, merged with H signal of minor anomer), 6.20 (d, J = 7.9 Hz, 1H), 5.39 (d, J = 5.2 Hz, 1H, partially merged with H signal of minor anomer), 5.34–5.29 (m, 1H, partially masked by residual solvent peak), 4.97 (t, J = 5.2 Hz, 1H), 4.60 (t, J = 5.0 Hz, 1H), 4.48 (dt, J = 8.5, 5.3 Hz, 1H), 4.29 (dd, J = 9.3, 6.4 Hz, 1H), 4.11 (dd, J = 9.3, 6.7 Hz, 1H), 2.05 (s, 3H), −OH signal not discernible; ¹³C NMR (75 MHz, CDCl₃) δ 170.41 (merged with C signal of minor anomer), 166.01, 133.56, 129.97 (2C), 129.48 (merged with C signal of minor anomer), 128.64 (2C, merged with C signal of major anomer), 96.59, 81.13, 81.00, 74.39, 70.25, 54.75, 23.25; HRMS (ESI, m/z) calcd for C₁₅H₁₇NO₆ (M+Na) 330.0954, found 330.0967.

3,6-Anhydro-2-acetamido-2-deoxy-5-O-isovaleryl-d-mannofuranose (Furanodictine B) (10)

10 was prepared from 29 using G.P4. Reaction was completed in 40 h. Crude was purified by silica gel column chromatography to yield the anomeric mixture 10 (84%) as yellow oil.

Minor anomer: ¹H NMR (400 MHz, CDCl₃) δ 6.19 (d, J = 8.0 Hz, 1H), 5.23 (d, J = 4.1 Hz, 1H), 5.18–5.14 (m, 1H), 4.97 (t, J = 4.9 Hz, 1H), 4.61 (t, J = 5.4 Hz, 1H), 4.22 (td, J = 6.4, 3.9 Hz, 1H), 4.06–4.04 (m, 1H, partially merged with H signal of major anomer), 3.82 (dd, J = 9.5, 5.9 Hz, 1H), 2.28–2.22 (m, 2H, merged with two H signals of major anomer), 2.15–2.09 (m, 1H, merged with H signal of major anomer), 2.04 (s, 3H), 0.97 (d, J = 6.8 Hz, 3H), 0.96 (d, J = 6.8 Hz, 3H), −OH signal not discernible; ¹³C NMR (100 MHz, CDCl₃) δ 172.40, 171.21, 103.74, 80.43, 79.83, 72.99, 70.89, 59.12, 43.10, 25.75, 23.24, 22.52 (merged with C-signal major anomer), 22.45.

Major anomer: ¹H NMR (400 MHz, CDCl₃) δ 6.19 (d, J = 8.0 Hz, 1H), 5.38 (d, J = 5.2 Hz, 1H), 5.13–5.08 (m, 1H), 4.82 (t, J = 5.0 Hz, 1H), 4.53 (t, J = 4.9 Hz, 1H), 4.44 (dt, J = 8.3, 5.3 Hz, 1H), 4.09 (dd, J = 9.0, 6.4 Hz, 1H, partially merged with H signal of minor anomer), 3.97 (dd, J = 9.1, 6.7 Hz, 1H), 2.28–2.22 (m, 2H, merged with two H signals of minor anomer), 2.15–2.09 (m, 1H, merged with H signal of minor anomer), 2.05 (s, 3H), 0.97 (d, J = 6.8 Hz, 3H), 0.96 (d, J = 6.8 Hz, 3H), −OH signal not discernible; ¹³C NMR (100 MHz, CDCl₃) δ 172.47, 170.44, 96.64, 80.94, 80.87, 73.57, 69.99, 54.76, 43.02, 25.67, 23.22, 22.52 (merged with C signal of minor anomer), 22.48; HRMS (ESI, m/z) calcd for C₁₃H₂₁NO₆ (M+Na) 310.1267, found 310.1258.

3,6-Anhydro-2-O-methyl-5-O-benzoyl-α-d-mannofuranosyl azide (38)

36 was prepared from 17c using G.P-1 after heating at 80 °C for 10h. Crude was purified by silica gel (100–200 mesh) column chromatography using 3% EA in hexane as an eluent to furnish 38 (71%) as an off-white semisolid. IR (KBr): ν_max 2113.50, 1724.48, 1274.50 cm^–1; ${[\alpha ]}_D^{25}$ = 156.29 (c 0.50, MeOH); ¹H NMR (400 MHz, CDCl₃) δ 8.08 (d, J = 7.9 Hz, 2H), 7.59 (t, J = 7.3 Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), 5.38–5.33 (m, 1H), 5.25 (d, J = 5.0 Hz, 1H), 5.03 (t, J = 5.0 Hz, 1H), 4.66 (t, J = 5.0 Hz, 1H), 4.18 (dd, J = 9.3, 6.4 Hz, 1H), 4.05 (dd, J = 9.3, 6.8 Hz, 1H), 3.63 (t, J = 5.2 Hz, 1H), 3.53 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 166.09, 133.57, 129.97 (2C), 129.38, 128.63 (2C), 94.88, 85.28, 80.66, 79.81, 73.83, 70.62, 59.01; HRMS (ESI, m/z) calcd for C₁₄H₁₅N₃O₅ (M+Na) 328.0909, found 328.0908.

3,6-Anhydro-2-O-ethyl-5-O-benzoyl-α-d-mannofuranosyl azide (39)

39 was prepared from 17d using G.P-1 after heating at 80 °C for 15h. Purification of crude product was done by silica gel (100–200 mesh) column chromatography using 7% EA in hexane as an eluent to obtain 39 (57%) as yellow oil. ${[\alpha ]}_D^{25}$ = 114.53 (c 0.25, MeOH); IR (KBr): ν_max 2113.58, 1724.56, 1274.37 cm^–1; ¹H NMR (300 MHz, CDCl₃) δ 8.10–8.06 (m, 2H), 7.61–7.55 (m, 1H), 7.48–7.36 (m, 2H), 5.38–5.32 (m, 1H), 5.24 (d, J = 5.2 Hz, 1H), 5.01 (t, J = 5.1 Hz, 1H), 4.62 (t-like, J = 5.1, 4.8 Hz, 1H), 4.16 (dd, J = 9.5, 6.3 Hz, 1H), 4.07 (dd, J = 9.5, 6.5 Hz, 1H), 3.79–3.59 (m, 3H), 1.28 (t, J = 6.9 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 166.11, 133.54, 129.96 (2C), 129.39, 128.61 (2C), 94.95, 83.66, 80.56, 80.03, 73.91, 70.67, 67.02, 15.39; HRMS (ESI, m/z) calcd for C₁₅H₁₇N₃O₅ (M+Na) 342.1066, found 342.1065.

3,6-Anhydro-2-O-butyl-5-O-benzoyl-α-d-mannofuranosyl azide (40)

40 was prepared from 17e using G.P-1 after heating at 100 °C for 17h. Purification of crude by silica gel (100–200 mesh) column chromatography using 7–10% EA in hexane as an eluent produced 40 (26%) as yellow oil. ${[\alpha ]}_D^{25}$ = 139.95 (c 0.48, MeOH); IR (KBr) ν_max 2113.11, 1725.27, 1273.71 cm^–1; ¹H NMR (400 MHz, DMSO-d ₆) δ 8.00 (d, J = 8.0 Hz, 2H), 7.69 (t, J = 7.4 Hz, 1H), 7.56 (t, J = 6.9 Hz, 2H), 5.32–5.28 (m, 1H), 5.25 (d, J = 5.6 Hz, 1H), 4.99 (t-like, J = 5.6. 4.8 Hz, 1H), 4.64 (t, J = 5.0 Hz, 1H), 4.09–4.05 (m, 1H), 3.94–3.91 (m, 1H), 3.77 (t, J = 5.3 Hz, 1H), 3.67–3.55 (m, 1H), 3.53–3.46 (m, 1H), 1.55–1.49 (m, 2H), 1.39–1.31 (m, 2H), 0.89 (t, J = 7.4 Hz, 3H); ¹³C NMR (100 MHz, DMSO-d ₆) δ 165.07, 133.50, 129.19 (2C), 129.06, 128.74 (2C), 93.74, 82.61, 80.16, 79.02, 73.76, 69.80, 69.59, 31.21, 18.59, 13.59; HRMS (ESI, m/z) calcd for C₁₇H₂₁N₃O₅ (M+H) 348.1559, found 348.1568.

3,6-Anhydro-2-O-methyl-α-d-mannofuranosyl azide (41)

41 was prepared from 38 using G.P-3. Crude mass was purified by silica gel (100–200 mesh) column chromatography using 20% EA in hexane as an eluent to obtain 41 (91%) as colorless oil. ${[\alpha ]}_D^{25}$ = 258.63 (c = 0.26, MeOH); IR (KBr): ν_max 3428.79, 2924.16, 2853.27, 2113.75 cm^–1; ¹H NMR (400 MHz, CD₃OD) δ 5.26 (d, J = 4.7 Hz, 1H), 4.67–4.63 (m, 2H), 4.29–4.24 (m, 1H), 3.93 (dd, J = 8.5, 6.7 Hz, 1H), 3.67 (t, J = 4.8 Hz, 1H), 3.54 (t, J = 8.4 Hz, 1H), 3.45 (s, 3H); ¹³C NMR (100 MHz, CD₃OD) δ 95.74, 86.38, 83.03, 80.41, 72.76, 72.24, 58.19; HRMS (ESI, m/z) calcd for C₇H₁₁N₃O₄ (M+Na) 224.0647, found 224.0646.

3,6-Anhydro-2-O-ethyl-α-d-mannofuranosyl azide (42)

42 was prepared from 39 using G.P-3. It was purified by silica gel (100–200 mesh) column chromatography using 20% EA in hexane as an eluent to furnish 42 (93%) as yellowish oil. ${[\alpha ]}_D^{25}$ = 140.80 (c 0.52, CHCl₃); IR (KBr): ν_max 3434.97, 2977.35, 2881.69, 2113.77 cm^–1; ¹H NMR (400 MHz, CDCl₃) δ 5.39 (d, J = 3.2 Hz, 1H), 4.76 (t, J = 5.5 Hz, 1H), 4.66 (t, J = 5.3 Hz, 1H), 4.28–4.22 (m, 1H), 4.01 (dd, J = 9.5, 5.5 Hz, 1H), 3.79–3.71 (m, 2H), 3.69 (dd, J = 5.1, 3.3 Hz, 1H), 3.61 (dq, J = 8.9, 7.0 Hz, 1H), 2.98 (d, J = 10.1 Hz, 1H), 1.25 (t, J = 7.0 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 96.12, 82.66, 82.16, 80.32, 75.20, 71.57, 67.22, 15.22; HRMS (ESI, m/z) calcd for C₈H₁₃N₃O₄ (M+Na) 238.0804, found 238.0805.

3,6-Anhydro-2-O-butyl-α-d-mannofuranosyl azide (43)

43 was prepared from 40 using G.P-3; purification of crude was done by silica gel (100–200 mesh) column chromatography using 20% EA in hexane as an eluent to obtain 43 (89%) as yellowish oil. ${[\alpha ]}_D^{25}$ = 240.11 (c 0.25, MeOH); IR (KBr): ν_max 3435.22, 2959.23, 2932.83, 2873.27, 2112.69 cm^–1; ¹H NMR (300 MHz, CDCl₃) δ 5.39 (d, J = 3.0 Hz, 1H), 4.76 (t-like, J = 5.7, 5.4 Hz, 1H), 4.66 (t-like, J = 5.1 Hz, 1H), 4.24 (brs, 1H), 4.00 (dd, J = 9.5, 5.4 Hz, 1H), 3.76 (dd, J = 9.5, 5.6 Hz, 1H), 3.72–3.65 (m, 2H), 3.52 (dt, J = 9.0, 6.6 Hz, 1H), 3.01 (brs, 1H), 1.64–1.55 (m, 2H, partially merged with solvent water peak), 1.44–1.34 (m, 2H), 0.92 (t, J = 7.3 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 96.20, 82.79, 82.17, 80.33, 75.25, 71.67, 71.51, 31.73, 19.14, 13.82; HRMS (ESI, m/z) calcd for C₁₀H₁₇N₃O₄ (M+Na) 266.1117, found 266.1116.

General Procedure of Triazole Construction for the Preparation of 46–47

To a solution of 38 (3 mol) in t-BuOH-H₂O (3:2) mixture (30 mL, for 200 mg substrate) were added anhydrous CuSO₄ (5.0 equiv), sodium ascorbate (0.3 equiv), and aryl or aliphatic alkyne (44 or 45) (1.0 equiv) and stirred at room temperature for 16 h. It was filtered and filtrate was concentrated. The residue was extracted with ethyl acetate (3 × 30 mL) and the organic layer was washed with water (3 × 30 mL), dried (Na₂SO₄), and concentrated. The crude mass on purification through silica gel (100–200 mesh) column chromatography using EA–hexane (1:4) as an eluent furnished the desired products.

3,6-Anhydro-2-O-methyl-5-O-benzoyl-α-d-mannofuranosyl (4′-o-Methoxyphenyl) Triazole (46)

46 was prepared by reacting 38 with 44 using the above procedure. Yield = 69% as yellow semisolid. ${[\alpha ]}_D^{25}$ = 44.37 (c 0.51, CHCl₃); ¹H NMR (400 MHz, CDCl₃) δ 8.33–8.31 (m, 1H), 8.09 (d, J = 7.8 Hz, 2H), 8.03 (s, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.46 (t, J = 7.8 Hz, 2H), 7.31 (t, J = 8.0 Hz, 1H), 7.07 (t, J = 7.5 Hz, 1H), 6.95 (d, J = 8.3 Hz, 1H), 6.07 (d, J = 5.4 Hz, 1H), 5.44–5.41 (m, 1H), 5.17 (t, J = 4.9 Hz, 1H), 4.95–4.93 (m, 1H), 4.76 (t, J = 5.4 Hz, 1H), 4.30–4.26 (m, 1H), 4.21–4.17 (m, 1H), 4.13–4.09 (m, 1H), 3.88 (s, 3H), 3.51 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 165.94, 155.79, 143.45, 133.53, 129.95 (2C), 129.33, 129.25, 128.60 (2C), 127.76, 123.18, 121.10, 118.97, 110.84, 91.64, 84.49, 81.34, 79.93, 73.96, 70.80, 59.14, 55.41; HRMS (ESI, m/z) calcd for C₂₃H₂₃N₃O₆ (M+H) 438.1660, found 438.1666.

3,6-Anhydro-2-O-methyl-5-O-benzoyl-α-d-mannofuranosyl (4′-n-Propyl) Triazole (47)

47 was prepared by reacting 38 with 45 using the procedure described above. Yield = 73% as a colorless semisolid. ${[\alpha ]}_D^{25}$ = 54.27 (c 0.51, CHCl₃); ¹H NMR (400 MHz, CDCl₃) δ 8.07 (d, J = 7.7 Hz, 2H), 7.59 (t, J = 7.5 Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), 7.20 (s, 1H), 5.95 (d, J = 5.5 Hz, 1H), 5.43–5.39 (m, 1H), 5.12 (t, J = 5.0 Hz, 1H), 4.88 (t, J = 4.8 Hz, 1H), 4.70 (t, J = 5.4 Hz, 1H), 4.25 (dd, J = 9.5, 6.4 Hz, 1H), 4.17 (dd, J = 9.6, 6.4 Hz, 1H), 3.49 (s, 3H), 2.65 (t, J = 7.7 Hz, 2H), 1.68–1.64 (m, 2H, partially merged with solvent H₂O), 0.94 (t, J = 7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 165.93, 133.56, 129.90 (2C), 129.29, 128.60 (2C), 121.02, 91.46, 84.35, 81.25, 79.78, 73.99, 70.75, 59.05, 27.58, 22.51, 13.86 (one triazole carbon signal not discernible); HRMS (ESI, m/z) calcd for C₁₉H₂₃N₃O₅ (M+H) 374.1710, found 374.1715.

3,6-Anhydro-2-O-methyl-α-d-mannofuranosyl (4′-o-Methoxyphenyl) Triazole (48)

48 was prepared from 46 using G.P-3. Purification was done by silica gel (100–200 mesh) column chromatography using 70% EA in hexane to obtain 48 (91%) as a colorless viscous liquid. ${[\alpha ]}_D^{25}$ = 83.87 (c 0.50, CHCl₃); ¹H NMR (400 MHz, CDCl₃) δ 8.38 (d, J = 7.7 Hz, 1H), 8.24 (s, 1H), 7.36 (t, J = 8.0 Hz, 1H), 7.12 (t, J = 7.6 Hz, 1H), 7.01 (d, J = 8.3 Hz, 1H), 6.13 (d, J = 4.2 Hz, 1H), 4.98 (t, J = 5.0 Hz, 1H), 4.88 (t, J = 5.1 Hz, 1H), 4.78 (t, J = 4.8 Hz, 1H), 4.39–4.38 (m, 1H), 4.13 (dd, J = 9.3, 6.0 Hz, 1H), 3.98 (s, 3H), 3.85 (dd, J = 9.2, 6.3 Hz, 1H), 3.54 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 155.67, 143.37, 129.23, 127.56, 123.03, 120.97, 118.64, 110.73, 92.10, 84.47, 82.92, 79.97, 73.89, 72.11, 59.09, 55.33; HRMS (ESI, m/z) calcd for C₁₆H₁₉N₃O₅ (M+H) 334.1394, found 334.1403.

3,6-Anhydro-2-O-methyl-α-d-mannofuranosyl (4′-n-Propyl) Triazole (49)

49 was prepared from 47 using G.P-3. Crude mass was purified by silica gel (100–200 mesh) column chromatography using 70% EA in hexane as an eluent to furnish 49 (95%) as a yellowish semisolid. ${[\alpha ]}_D^{25}$ = 87.30 (c 1.02, CHCl₃); ¹H NMR (400 MHz, CDCl₃) δ 7.46 (s, 1H), 6.01 (d, J = 4.4 Hz, 1H), 4.91 (t, J = 5.1 Hz, 1H), 4.81 (t, J = 5.1 Hz, 1H), 4.68 (t, J = 4.8 Hz, 1H), 4.37–4.32 (m, 1H), 4.09 (dd, J = 9.5, 6.1 Hz, 1H), 3.81 (dd, J = 9.4, 6.4 Hz, 1H), 3.50 (s, 3H), 2.72 (t, J = 7.7 Hz, 2H), 1.74–1.67 (m, 2H, merged with solvent H₂O), 0.98 (t, J = 7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 148.55, 120.86, 91.96, 84.71, 83.00, 79.83, 73.70, 72.28, 59.02, 27.51, 22.56, 13.81; HRMS (ESI, m/z) calcd for C₁₂H₁₉N₃O₄ (M+Na) 292.1273, found 292.1274.

3,6-Anhydro-2-O-methyl-5-O-benzoyl-α- d-mannofuranosyl-N-acetamide (50)

50 was prepared from 38 using G.P-2. Crude product was purified by neutral alumina (70–230 mesh) column chromatography using 45% EA in hexane as an eluent to furnish 50 (78%) as a white solid. mp 184–185 °C; ${[\alpha ]}_D^{25}$ = 131.78 (c 0.25, MeOH); ¹H NMR (300 MHz, CD₃OD) δ 8.11–8.08 (m, 2H), 7.62–7.57 (m, 1H), 7.51–7.45 (m, 2H), 5.53 (d, J = 7.9 Hz, 1H), 5.39–5.33 (m, 1H), 4.95 (t, J = 5.4 Hz, 1H), 4.62 (t, J = 4.9 Hz, 1H), 4.12–4.01 (m, 2H), 3.73 (dd, J = 7.9, 4.9 Hz, 1H), 3.48 (s, 3H), 1.92 (s, 3H); ¹³C NMR (75 MHz, CD₃OD) δ 172.50, 166.28, 132.97, 129.54 (2C), 129.49, 128.15 (2C), 83.57, 82.31, 78.98, 78.38, 74.50, 70.98, 57.12, 21.43; HRMS (ESI, m/z) calcd for C₁₆H₁₉NO₆ (M+Na) 344.1110, found 344.1122.

3,6-Anhydro-2-O-methyl-α-d-mannofuranosyl-N-acetamide and 3,6-Anhydro-2-O-methyl-β-d-mannofuranosyl-N-acetamide (52)

Benzoyl deprotection of 50 using G.P-3 furnished a crude mass, which on purification by neutral alumina (70–230 mesh) column chromatography using 70% EA in hexane as an eluent produced anomeric mixture 52 (93%) as a colorless liquid. Separation of above anomeric mixture by neutral alumina column chromatography was unsuccessful, though a tiny quantity of minor anomer was separated as a colorless liquid in a single effort out of several trials. We recorded NMR spectra of both pure minor anomer and the anomeric mixture.

Minor anomer (pure form): ${[\alpha ]}_D^{25}$ = 47.99 (c 0.25, MeOH); ¹H NMR (300 MHz, CD₃OD) δ 5.31 (d, J = 7.8 Hz, 1H), 4.62 (t, J = 4.5 Hz, 1H), 4.54 (t-like, J = 4.8, 4.2 Hz, 1H), 4.27–4.20 (m, 1H), 3.97 (dd, J = 8.6, 6.9 Hz, 1H), 3.76 (dd, J = 7.8, 4.6 Hz, 1H), 3.54 (t, J = 8.5 Hz, 1H), 3.44 (s, 3H), 2.00 (s, 3H); ¹³C NMR (75 MHz, CD₃OD) δ 173.92, 84.89, 83.22, 80.89, 78.89, 73.45, 72.39, 57.47, 21.91.

Major anomer (present in the anomeric mixture): ¹H NMR (400 MHz, CD₃OD) δ 5.75 (d, J = 5.9 Hz, 1H), 4.59–4.56 (m, 1H), 4.41 (t, J = 6.1 Hz, 1H), 4.30–4.26 (m, 1H), 4.00–3.95 (m, 1H, partially merged with peak of minor anomer), 3.89 (t, J = 7.7 Hz, 1H), 3.78–3.73 (m, 1H, merged with peak of minor anomer), 3.46 (s, 3H), 2.01 (s, 3H); ¹³C NMR (100 MHz, CD₃OD) δ 173.32, 81.72, 81.50, 80.65, 80.51, 73.45, 72.40, 58.45, 22.29; HRMS (ESI, m/z) calcd for C₉H₁₅NO₅ (M+Na) 240.0848, found 240.0847.

Butyl-3,6-anhydro-5-O-benzoyl-β-d-mannofuranoside (54)

17e (2.5 g, 7.75 mmol) was dissolved in dry DCM (50 mL) along with TEMPO (15 mol %, 181 mg) and BAIB (1.3eq, 3.25g). The resultant mixture was stirred at room temperature for 12h. The reaction mixture was diluted with DCM (50 mL) and washed with saturated aqueous NaHCO₃ (3 × 80 mL) solution and then water (2 × 50 mL). The organic layer was dried (Na₂SO₄) and evaporated to obtain crude ketone intermediate 53 as a viscous orange residue, which was used for next step without further purification. To the solution of 49 in THF (40 mL) was added NaBH₄ (1.5 equiv, 440 mg) and stirred at room temperature for 15 min. It was quenched by slow addition of aqueous NH₄Cl under an ice-cold condition. The solvent of the reaction mixture was evaporated under reduced pressure, and the residue was extracted with DCM (3 × 50 mL). The organic layer was washed with water (2 × 50 mL), dried (Na₂SO₄) and concentrated. The crude product was purified by silica gel (100–200 mesh) column chromatography using 15% EA in hexane as an eluent to furnish 54 (82% in two steps) as a white solid. mp 63 °C; ${[\alpha ]}_D^{25}$ = 94.64 (c 0.50, MeOH); ¹H NMR (400 MHz, DMSO-d ₆) δ 7.99–7.96 (m, 2H), 7.71–7.66 (m, 1H), 7.57–7.52 (m, 2H), 5.12 (ddd, J = 9.2, 7.7, 5.5 Hz, 1H), 4.80 (t, J = 5.2 Hz, 1H, partially merged with a doublet), 4.78 (d, J = 5.2 Hz, 1H), 4.46 (t, J = 5.4 Hz, 1H, partially merged with a doublet), 4.43 (d, J = 10.1 Hz, 1H), 4.11 (t-like, J = 8.0, 7.6 Hz, 1H), 4.04 (dd, J = 9.3, 7.8 Hz, 1H), 3.96 (dt, J = 10.4, 5.5 Hz, 1H), 3.63 (dt, J = 9.5, 6.9 Hz, 1H), 3.28 (dt, J = 9.4, 6.9 Hz, 1H), 1.55–1.48 (m, 2H), 1.29–1.22 (m, 2H), 0.82 (t, J = 7.4 Hz, 3H); ¹³C NMR (100 MHz, DMSO-d ₆) δ 165.01, 133.69, 129.17 (3C), 128.85 (2C), 101.07, 80.09, 78.30, 74.16, 72.99, 67.61, 67.45, 31.11, 18.82, 13.77; HRMS (ESI, m/z) calcd for C₁₇H₂₂O₆ (M+Na) 345.1314, found 345.1310.

Butyl-3,6-anhydro-β-d-mannofuranoside (55)

55 was prepared from 54 using G.P-3. The crude product was purified by neutral alumina (70–230 mesh) column chromatography using 50–60% EA in hexane as an eluent to obtain 55 (95%) as colorless oil. ${[\alpha ]}_D^{25}$ = −14.67 (c 0.50, MeOH); ¹H NMR (400 MHz, DMSO-d ₆) δ 4.80 (d, J = 5.2 Hz, 1H), 4.65 (d, J = 6.2 Hz, 1H), 4.32 (t, J = 4.6 Hz, 1H), 4.27 (t-like, J = 5.2, 4.4 Hz, 1H), 4.10–4.02 (m, 2H), 3.94–3.89 (m, 1H), 3.78 (dt, J = 9.5, 6.6 Hz, 1H), 3.70 (t, J = 7.5 Hz, 1H), 3.60 (dd, J = 9.7, 7.3 Hz, 1H), 3.35–3.29 (m, 1H, partially merged with solvent H₂O), 1.55–1.48 (m, 2H), 1.39–1.30 (m, 2H), 0.88 (t, J = 7.3 Hz, 3H); ¹³C NMR (100 MHz, DMSO-d ₆) δ 100.99, 80.52, 79.88, 73.15, 71.57, 69.75, 67.43, 31.13, 18.86, 13.80; HRMS (ESI, m/z) calcd for C₁₀H₁₈O₅ (M+Na) 241.1052, found 241.1050.

Butyl-3,6-anhydro-2-azido-2-deoxy-5-O-benzoyl-β-d-glucofuranoside (56)

56 was prepared from 54 using G.P-1. It was heated at 80 °C for 8h. Crude was purified by silica gel (100–200 mesh) column chromatography using 10% EA in hexane as an eluent to furnish 56 (86%) as yellowish oil. ${[\alpha ]}_D^{25}$ = 34.08 (c 0.53, MeOH); IR (KBr): ν_max 2108.42, 1726.34, 1273.54 cm^–1; ¹H NMR (400 MHz, DMSO-d ₆) δ 7.99–7.97 (m, 2H), 7.71–7.67 (m, 1H), 7.57–7.52 (m, 2H), 5.18 (ddd, J = 8.6, 7.4, 5.6 Hz, 1H), 5.06 (s, 1H), 5.00 (t, J = 5.4 Hz, 1H), 4.67 (dd, J = 5.1, 1.0 Hz, 1H), 4.17–4.13 (m, 2H), 3.99 (t, J = 8.6 Hz, 1H), 3.58 (dt, J = 9.4, 6.9 Hz, 1H), 3.35–3.30 (m, 1H, merged with solvent H₂O), 1.49–1.42 (m, 2H), 1.23–1.16 (m, 2H), 0.80 (t, J = 7.4 Hz, 3H); ¹³C NMR (100 MHz, DMSO-d ₆) δ 164.97, 133.73, 129.21 (2C), 129.07, 128.85 (2C), 107.19, 85.18, 81.07, 73.38, 69.76, 68.32, 67.37, 30.84, 18.74, 13.66; HRMS (ESI, m/z) calcd for C₁₇H₂₁N₃O₅ (M+H) 348.1559, found 348.1573.

Butyl-3,6-anhydro-2-acetamido-2-deoxy-5-O-benzoyl-β-d-glucofuranoside (57)

57 was prepared from 56 using G.P-2. Crude mass was purified by repeated silica gel (100–200 mesh) column chromatography using 50% EA in hexane as an eluent to obtain 57 (88%) as white solid. m.p 84–85 °C; ¹H NMR (400 MHz, DMSO-d ₆) δ 8.20 (d, J = 7.4 Hz, 1H), 7.99 (d, J = 8.1 Hz, 2H), 7.69 (t, J = 7.4 Hz, 1H), 7.55 (t, J = 7.1 Hz, 2H), 5.19–5.13 (m, 1H), 5.02 (t, J = 5.5 Hz, 1H), 4.86 (s, 1H), 4.45 (d, J = 5.0 Hz, 1H), 4.12 (t, J = 7.8 Hz, 1H), 4.07 (d, J = 7.2 Hz, 1H), 4.02 (t, J = 8.4 Hz, 1H), 3.58 (dt, J = 9.5, 7.0 Hz, 1H), 3.32–3.28 (m, 1H), 1.84 (s, 3H), 1.51–1.44 (m, 2H), 1.25–1.19 (m, 2H), 0.82 (t, J = 7.4 Hz, 3H); ¹³C NMR (100 MHz, DMSO-d ₆) δ 168.92, 164.97, 133.56, 129.16 (2C), 129.09, 128.73 (2C), 108.54, 86.19, 80.96, 73.70, 67.95, 66.97, 61.67, 30.86, 22.39, 18.71, 13.59; HRMS (ESI, m/z) calcd for C₁₉H₂₅NO₆ (M+Na) 364.1760, found 364.1771.

Butyl-3,6-anhydro-2-azido-2-deoxy-β-d-glucofuranoside (58)

58 was prepared from 56 using G.P-3 and it was purified by neutral alumina (70–230 mesh) column chromatography using 30% EA in hexane as an eluent to obtain 58 (95%) as colorless oil. ${[\alpha ]}_D^{25}$ = −28.96 (c 0.51, MeOH); IR (KBr): ν_max 3436.30, 2959.73, 2855.10, 2108.56 cm^–1; ¹H NMR (400 MHz, DMSO-d ₆) δ 5.03 (s, 1H), 4.91 (d, J = 5.8 Hz, 1H), 4.51 (t, J = 4.9 Hz, 1H), 4.46 (d, J = 4.6 Hz, 1H), 4.12–4.05 (m, 1H), 4.01 (s, 1H), 3.81–3.71 (m, 2H), 3.54 (t-like, J = 9.2, 7.6 Hz, 1H), 3.40–3.34 (m, 1H), 1.53–1.46 (m, 2H), 1.36–1.27 (m, 2H), 0.88 (t, J = 7.4 Hz, 3H); ¹³C NMR (100 MHz, DMSO-d ₆) δ 106.94, 84.47, 83.07, 70.93, 69.85 (d, J = 1.6 Hz, 1C), 69.76, 67.26, 30.88, 18.79, 13.64; HRMS (ESI, m/z) calcd for C₁₀H₁₇N₃O₄ (M+Na) 266.1117, found 266.1116.

Butyl-3,6-anhydro-2-acetamido-2-deoxy-β-d-glucofuranoside (59)

59 was prepared from 57 using G.P-3. The crude product was purified by neutral alumina (70–230 mesh) column chromatography using 65% EA in hexane as an eluent to obtain 59 (97%) as white solid. m.p 81–82 °C; ${[\alpha ]}_D^{25}$ = −1.21 (c 0.49, MeOH); ¹H NMR (400 MHz, DMSO-d ₆) δ 8.12 (d, J = 7.5 Hz, 1H), 4.86 (s, 1H), 4.79 (d, J = 6.0 Hz, 1H), 4.53 (t, J = 4.6 Hz, 1H), 4.23 (d, J = 4.5 Hz, 1H), 4.09–4.02 (m, 1H), 3.97 (d, J = 7.6 Hz, 1H), 3.74 (dt, J = 9.5, 6.6 Hz, 1H), 3.69 (t, J = 7.5 Hz, 1H), 3.56 (dd, J = 9.5, 7.4 Hz, 1H), 3.31–3.27 (m, 1H, partially merged with solvent H₂O), 1.81 (s, 3H), 1.52–1.45 (m, 2H), 1.35–1.26 (m, 2H), 0.88 (t, J = 7.3 Hz, 3H); ¹³C NMR (100 MHz, DMSO-d ₆) δ 169.03, 108.44, 85.58, 83.35, 71.25, 69.84, 66.95, 61.61, 31.03, 22.47, 18.92, 13.79; HRMS (ESI, m/z) calcd for C₁₂H₂₁NO₅ (M+Na) 282.1317, found 282.1308.

Butyl-3,6-anhydro-2-acetamido-2-deoxy-5-O-isovaleryl-β-d-glucofuranoside (60)

60 was prepared from 59 using G.P-5. Crude product was purified by silica gel (100–200 mesh) column chromatography using 55% EA in hexane as an eluent to obtain 60 (95%) as white solid. mp (67–68 °C); ${[\alpha ]}_D^{25}$ = 61.34 (c 0.25, MeOH); ¹H NMR (400 MHz, DMSO-d ₆) δ 8.17 (d, J = 7.5 Hz, 1H), 4.92–4.86 (m, 2H), 4.85 (s, 1H), 4.36 (d, J = 4.5 Hz, 1H), 4.02 (d,J = 7.6 Hz,1H), 3.98–3.95 (m, 1H), 3.83–3.79 (m, 1H), 3.65 (dt, J = 9.5, 6.8 Hz, 1H), 3.33–3.29 (m, 1H, merged with solvent H₂O peak), 2.22 (d, J = 7.1 Hz, 2H), 2.05–1.95 (m, 1H), 1.81 (s, 3H), 1.54–1.47 (m, 2H), 1.36–1.27 (m, 2H), 0.92 (d, J = 6.8 Hz, 6H), 0.88 (t, J = 7.6 Hz, 3H); ¹³C NMR (100 MHz, DMSO-d ₆) δ 171.70, 169.06, 108.42, 86.09, 80.77, 72.99, 67.62, 66.99, 61.65, 42.44, 30.97, 25.37, 22.48, 22.10 (2C), 18.97, 13.77; HRMS (ESI, m/z) calcd for C₁₇H₂₉NO₆ (M+Na) 366.1893, found 366.1882.

3,6-Anhydro-2-azido-2-deoxy-5-O-isovaleryl-d-glucofuranose (Furanodictine A) (9)

9 was synthesized from 60 using G.P4. Reaction was completed in 40 h. Crude mass was purified by silica gel (100–200 mesh) column chromatography using isocratic EA as an eluent to obtain anomeric mixture 9 (85%) as a yellow oily liquid.

Minor anomer: ¹H NMR (300 MHz, CDCl₃) δ 5.95 (d, J = 7.5 Hz, 1H), 5.24 (d, J = 8.3 Hz, 1H), 5.12–5.07 (m, 1H), 4.93–4.87 (m, 1H, overlapped with another proton signal of major anomer), 4.40–4.35 (m, 1H, merged with another proton signal of major anomer), 4.24 (brs,1H), 4.13 (dd, J = 10.0, 4.4 Hz, 1H), 3.90 (dd, J = 10.0, 6.0 Hz, 1H), 2.30–2.23 (m, 2H, overlapped with another two proton signals of major anomer), 2.14–2.05 (m, 1H, merged with another proton signal of major anomer), 1.99 (s, 3H), 0.96 (d, J = 6.6 Hz, 6H, merged with another six proton signals of major anomer), −OH signal not discernible; ¹³C NMR (75 MHz, CDCl₃) δ 172.78, 170.37, 103.64, 86.80, 81.98, 73.30, 71.23, 61.05, 43.03, 25.60, 23.17, 22.52 (one signal merged with another carbon signal of major anomer).

Major anomer: ¹H NMR (300 MHz, CDCl₃) δ 6.23 (d, J = 7.9 Hz, 1H), 5.54 (d, J = 4.8 Hz, 1H), 5.02–4.95 (m, 1H), 4.88 (t-like, J = 5.7, 5.4 Hz, 1H, merged with another proton signal of minor anomer), 4.56 (dd, J = 5.5, 3.9 Hz, 1H), 4.40–4.35 (m, 1H, merged with another proton signal of minor anomer), 4.05 (dd, J = 9.4, 6.1 Hz, 1H), 3.81 (dd, J = 9.4, 7.3 Hz, 1H, merged with another proton signal of minor anomer), 2.26–2.23 (m, 2H, partially merged with another two proton signals of minor anomer), 2.14–2.05 (m, 1H, merged with another proton signal of minor anomer), 2.03 (s, 3H), 0.96 (d, J = 6.6 Hz, 6H, merged with another six proton signals of minor anomer), −OH signal not discernible;¹³C NMR (75 MHz, CDCl₃) δ 172.78, 170.78, 98.26, 87.13, 78.07, 72.37, 68.74, 58.86, 43.12, 25.79, 23.30, 22.50, 22.46; HRMS (ESI, m/z) calcd for C₁₃H₂₁NO₆ (M+Na) 310.1267, found 310.1273.

Butyl-3,6-anhydro-5-O-benzoyl-α-d-mannofuranoside (62) and Butyl-3,6-anhydro-5-O-benzoyl-α-d-glucofuranoside (17b)

Compound 17b (500 mg, 1.55 mmol) was oxidized to obtain ketone intermediate 61 using the procedure as adopted for the preparation of 53 from 17e. Then, 61 was subjected to NaBH₄ reduction to obtain the crude mass using the procedure as applied for the preparation of 54 from 53. Attempted purification of the crude product over silica gel (100–200 mesh) column chromatography using 15% EA in hexane as an eluent furnished the diastereomeric mixture of 62 and 17b as yellowish oil with 84% yield in the ratio of 2:1 as predicted from the ¹H NMR spectrum.

Major isomer (62): ¹H NMR (400 MHz, CDCl₃) δ 8.12–8.03 (m, 2H, merged with a signal of 17b), 7.62–7.53 (m, 1H, merged with a signal of 17b), 7.50–7.41 (m, 2H, merged with a signal of xx), 5.37 (q, J = 5.8 Hz, 1H), 5.02 (d, J = 1.4 Hz, 1H), 4.94–4.89 (m, 1H, merged with a signal of 17b), 4.73 (t, J = 5.7 Hz, 1H), 4.24 (dd, J = 9.3, 5.8 Hz, 1H), 4.09–4.05 (m, 2H); 3.60 (dt, J = 9.7, 6.7 Hz, 1H), 3.34 (dt, J = 9.7, 6.6 Hz, 1H), 2.94 (s, 1H), 1.57–1.45 (m, 2H, merged with a signal of 17b), 1.36–1.23 (m, 2H, merged with a signal of 17b), 0.87 (t, J = 7.6 Hz, 3H, merged with a signal of 17b); ¹³C NMR (100 MHz, CDCl₃) δ 166.06, 133.47, 130.02, 129.70, 128.59 (merged with a signal of 17b), 110.58, 81.43, 79.88, 75.21, 73.08, 71.36, 68.02, 31.64, 19.31, 13.92.

Minor isomer (17b): ¹H NMR (400 MHz, CDCl₃) δ 8.12–8.03 (m, 2H, merged with a signal of 62), 7.62–7.53 (m, 1H, merged with a signal of 62), 7.50–7.41 (m, 2H, merged with a signal of 62), 5.27 (q, J = 6.0 Hz, 1H), 5.11 (d, J = 4.2 Hz, 1H), 4.92 (m, 1H, merged with a signal of 62), 4.51 (dd, J = 5.3, 2.6 Hz, 1H), 4.18 (s, 1H), 4.11 (dd, J = 9.4, 5.9 Hz, 1H), 3.94 (dd, J = 9.5, 6.4 Hz, 1H), 3.73 (dt, J = 9.6, 6.6 Hz, 1H), 3.42 (dt, J = 9.7, 6.6 Hz, 1H), 2.71 (brs, 1H), 1.57–1.45 (m, 2H, merged with a signal of 62), 1.36–1.23 (m, 2H, merged with a signal of 62), 0.88 (t, J = 7.6 Hz, 3H, merged with a signal of 62); ¹³C NMR (100 MHz, CDCl₃) δ 165.99, 133.43, 129.93, 129.70, 128.59 (merged with a signal of 62), 103.95, 87.98, 78.53, 73.36, 69.43, 68.89, 31.61, 19.27, 13.89.

HRMS (ESI, m/z) calcd for C₁₇H₂₂O₆ (M+Na) 345.1314, found 345.1306

Butyl-3,6-anhydro-2-deoxy-2-a-azido-5-O-benzoyl-α-d-glucofuranoside (65) and Butyl-3,6-anhydro-2-azido-2-deoxy-5-O-benzoyl-α-d-mannofuranoside (21)

Compounds 65 and 21 were prepared from the mixture of 62 and 17b using G.P-1 after heating at 80 °C for 5h. The crude product was purified by silica gel (100–200 mesh) column chromatography using 2% EA in hexane as an eluent to furnish 65 (45% from 17b) as yellowish oil and 21 (22% from 17b) as a white solid.

Compound 65. ${[\alpha ]}_D^{25}$ = 111.5 (c 0.38, MeOH); IR (KBr) 2979.42, 2929.98, 2873.25, 2110.15, 1727.28, 1273.55 cm^–1; ¹H NMR (400 MHz, CDCl₃) δ 8.08–8.05 (m, 2H), 7.61–7.57 (m, 1H), 7.48–7.44 (m, 2H), 5.29 (q, J = 5.7 Hz, 1H), 5.17 (d, J = 4.2 Hz, 1H), 4.94 (t, J = 5.8 Hz, 1H), 4.75 (dd, J = 5.9, 4.3 Hz, 1H), 4.15 (dd, J = 9.8, 5.6 Hz, 1H), 3.99 (dd, J = 9.8, 6.0 Hz, 1H), 3.72–3.66 (m, 2H), 3.38 (dt, J = 9.6, 6.6 Hz, 1H), 1.57–1.51 (m, 2H), 1.39–1.31 (m, 2H), 0.89 (t, J = 7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ165.85, 133.51, 129.92, 129.59, 128.63, 105.12, 84.86, 78.40, 72.78, 69.86, 68.75, 66.49, 31.63, 19.27, 13.90; HRMS (ESI, m/z) calcd for C₁₇H₂₁N₃O₅ (M+Na) 370.1379, found 370.1372.

Butyl-3,6-anhydro-2-deoxy-2-azido-α-d-glucofuranoside (66)

66 was prepared from 65 using G.P-3. Crude mass was purified by silica gel (100–200 mesh) column chromatography using 20% EA in hexane as an eluent to produce 66 (92%) as colorless oil. ${[\alpha ]}_D^{25}$ = 190.9 (c 0.36, MeOH); IR (KBr) 2959.52, 2934.92, 2873.84, 2110.84 cm^–1; ¹H NMR (400 MHz, CDCl₃)­δ 5.25 (d, J = 4.3 Hz, 1H), 4.69–4.63 (m, 2H), 4.21 (q, J = 5.8 Hz, 1H), 3.95 (dd, J = 9.6, 5.5 Hz, 1H), 3.79 (dt, J = 9.5, 6.6 Hz, 1H), 3.65 (t, J = 4.2 Hz, 1H), 3.61 (dd, J = 9.6, 6.4 Hz, 1H), 3.51 (dt, J = 9.5, 6.5 Hz, 1H), 2.42 (brs, 1H), 1.63–1.58 (m, 2H), 1.45–1.35 (m, 2H), 0.93 (t, J = 7.3 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 105.23, 84.72, 79.36, 72.52, 70.93, 68.81, 66.75, 31.64, 19.32, 13.90; HRMS (ESI, m/z) calcd for C₁₀H₁₇N₃O₄ (M+Na) 266.1117, found 266.1106.

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.5c05437.

• Additional experimental details of single-crystal X-ray structure of 21, 50, and 54 spectroscopy and analytical data for all compounds (PDF)

• X-ray crystal data for compound 21 (CIF)

• X-ray crystal data for compound 50 (CIF)

• X-ray crystal data for compound 54 (CIF)

CCDC 2425143–2425145 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: + 44 1223 336033.

The authors declare no competing financial interest.