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. Author manuscript; available in PMC: 2010 Jan 5.
Published in final edited form as: Carbohydr Res. 2008 Oct 14;344(1):140–144. doi: 10.1016/j.carres.2008.10.007

Dimethylthexylsilyl 2-acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-β-d-glucopyranoside, dimethylthexylsilyl 3,4,6-tri-O-benzyl-β-d-mannopyranosyl-(1→4)-2-acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-β-d-glucopyranoside, and dimethylthexylsilyl 2-O-(benzylsulfonyl)-3,4,6-tri-O-benzyl-β-d-mannopyranosyl-2-acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-β-d-glucopyranoside: synthesis of authentic samples*

David Crich a,b,†, Ming Li a, Prasanna Jayalath b
PMCID: PMC2669226  NIHMSID: NIHMS88110  PMID: 18954867

Abstract

Dimethylthexylsilyl 2-acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-β-d-glucopyranoside was prepared by reduction of the corresponding 4,6-O-(4-methoxybenzylidene) acetal with sodium cyanoborohydride and trifluoroacetic acid. This alcohol was coupled to 2-O-benzoyl-3,4,6-tri-O-benzyl-α-d-glucopyranosyl trichloroacetimidate to give a β-glucoside that was converted to dimethylthexylsilyl 3,4,6-tri-O-benzyl-β-d-mannopyranosyl-(1→4)-2-acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-β-d-glucopyranoside by saponification, Dess-Martin oxidation and sodium borohydride reduction. Sulfonylation then gave dimethylthexylsilyl 2-O-(benzylsulfonyl)-3,4,6-tri-O-benzyl-β-d-mannopyranosyl-(1→4)-2-acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-β-d-glucopyranoside.

Keywords: Glycosylation, Uloside, Mannoside

The NMR spectral data for dimethylthexylsilyl 2-acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-β-d-glucopyranoside (4) and dimethylthexylsilyl 3,4,6-tri-O-benzyl-β-d-mannopyranosyl-(1→4)-2-acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-β-d-glucopyranoside (11), as described by Schmidt and co-workers,1 is incorrect.2,3 We describe unambiguous syntheses of authentic samples of both compounds and of the 2-benzylsulfonyl derivative (12) of 11, and provide full characterization data for all three compounds.

Synthesis of the glycosyl acceptor 4 began with the known dimethylthexylsilyl glycoside 14 from which the esters were removed with catalytic sodium methoxide to give a triol that was immediately converted to the 4-methoxybenzylidene acetal 2 (Scheme 1). The 3-O-allyl ether 6 was then obtained by treatment with sodium hydride and allyl bromide. Reductive cleavage of the 4-methoxybenzylidene acetal with sodium cyanoborohydride and trifluoroacetic acid5 finally gave the acceptor 4 in 70% yield together with 6% of the 4-O-(4-methoxybenzyl) ether 5 (Scheme 1). The regioselectivity of the reductive ring opening reaction is supported by the chemical shift (δ 70.7) of C-6 in the 6-O-(4-methoxybenzyl) isomer 4, which is consistent of that of C-6 in a closely related compound, allyl 3-O-benzyl-2-deoxy-2-acetamido-β-d-glucopyranoside, which was accessed by a different route.6 Additional confirmation was obtained by acetylation of both 4 and 5, giving 6 and 7, respectively, when the anticipated chemical shift changes were observed in the NMR spectra.

Scheme 1.

Scheme 1

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Synthesis of acceptor 4

Adapting the classical Lindberg approach to β-mannosides,7,8 2-O-benzoyl-3,4,6-tri-O-benzyl-α-d-glucopyranosyl trichloroactimidate (8)9 was activated with trimethylsilyl triflate10 in the presence of 4, leading to the isolation of the β-glucoside 9 in 51% yield (Scheme 2). Saponification gave the alcohol 10, Dess-Martin oxidation11 of which then provided a uloside that was immediately reduced with sodium borohydride to give the β-mannoside 11 in 84% yield along with 4.5% of the gluco-isomer 10. Finally, sulfonylation of 11 with benzylsulfonyl chloride in pyridine gave 12 in 97% yield (Scheme 2).

Scheme 2.

Scheme 2

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Unambiguous synthesis of the β-mannosides 11 and 12

1. Experimental

1.1. General Methods

Optical rotations were determined with an Autopol III polarimeter for solutions in CHCl3. NMR spectra were recorded for CDCl3 solutions with a Varian 400 or 500 MHz spectrometer. Chemical shifts are in ppm downfield from tetramethylsilane. High resolution mass spectra were recorded with a Waters Micromass-LCT-Premier-XE instrument.

1.2. Dimethylthexylsilyl 2-Acetamido-4,6-di-O-(4-methoxybenzylidene)-2-deoxy-β-d-glucopyranoside (2)

To a solution of 14 (3.38 g, 6.89 mmol) in MeOH–CH2Cl2 (1:1 v:v, 30 mL) was added a solution of NaOMe in MeOH (25 wt%, 0.2 mL, 0.88 mmol). The resulting mixture was stirred for 2.5 h at ambient temp under N2 atmosphere. Monitoring by TLC (MeOH– CH2Cl2 1:4) indicated that the reaction went to completion. The reaction was neutralized with Amberlist-15 resin (H+), filtered and the filtrate was concentrated to furnish a white foam, which was dissolved in DMF (20 mL). PPTS (184 mg, 0.73 mmol) and p-methoxybenzaldehyde dimethyl acetal (1.40 mL, 8.26 mmol) were added. The mixture was evaporated on a rotary evaporator at 50 °C to remove the methanol produced during the reaction. After 2 h TLC (EtOAc–hexane 1:3) showed that the reactant was completely consumed. The mixture was poured into 1 N aq NaHCO3 and extracted with CH2Cl2. The organic phase was washed with brine, dried over Na2SO4, and concentrated. The residue was subjected to silica gel column chromatography (EtOAc–CH2Cl2 3:2 → 2:1) to give 2 (2.22 g, 4.62 mmol, 67%). [α]d22 = −49.7 (c 1.1); 1H NMR (400 MHz) δ 7.40 (d, 2 H, J = 8.8 Hz, Ar-H), 6.86 (d, 2 H, J = 8.0 Hz, Ar-H), 5.83 (d, 1 H, J = 6.7 Hz, CH3CONH), 5.47 (s, 1 H, PhCHO2), 4.87 (d, 1 H, J = 8.0 Hz, H-1), 4.23 (dd, 1 H, J = 3.2, 10.0 Hz, H-6a), 4.18 (br. s, 1 H, OH), 4.02 (t, 1 H, J = 9.9 Hz, H-3), 3.77 (s, 3 H, OCH3), 3.73 (t, 1 H, J = 10.2 Hz, H-6b), 3.52 (t, 1 H, J = 9.2 Hz, H-4), 3.48–3.40 (m, 2 H, H-5, H-2), 1.99 (s, 3 H, CH3CONH), 1.65–1.58 (m, 1 H, SiC(CH3)2CH(CH3)2), 0.88–0.84 (m, 12 H, SiC(CH3)2CH(CH3)2), 0.15 (s, 3 H, SiCH3), 0.14 (s, 3 H, SiCH3); 13C NMR (100 MHz) δ 171.8, 160.4, 129.9, 127.9, 113.8, 102.0, 96.2, 81.9, 71.4, 68.8, 66.6, 61.0, 55.5, 34.2, 25.0, 23.8, 20.3, 20.2, 18.8, 18.7, −1.5, −3.2. ESIMS m/z Calcd for C24H39NO7SiNa [M + Na+]: 504.2394. Found: 504.2407.

1.3. Dimethylthexylsilyl 2-Acetamido-3-O-allyl-4,6-di-O-(4-methoxybenzylidene)-2-deoxy-β-d-glucopyranoside (3)

To a solution of alcohol 2 (2.15 g, 4.46 mmol) in anhydr DMF (15 mL) was added 60% NaH in mineral oil (284 mg, 7.10 mmol) at 0 °C under N2 atmosphere. After stirring for 10 min, allyl bromide (0.50 mL, 5.91 mmol) was added. The resulting mixture was stirred for 30 min at 0 °C, then was allowed to warm to ambient temperature and stirred for another 1.5 h. The mixture was poured into aq NH4Cl and extracted with CH2Cl2.

The organic phase was washed with brine, dried over Na2SO4, and concentrated. The residue was subjected to silica gel column chromatography to furnish 3 (1.59 g, 3.04 mmol, 68%). [α]d22 = −14.6 (c 1.0); 1H NMR (400 MHz) δ 7.38 (d, 2 H, J = 8.0 Hz, Ar-H), 6.87 (d, 2 H, J = 8.0 Hz, Ar-H), 5.93 (br. s, 1 H, CH3CONH), 5.89–5.81 (m, 1 H, CH2CH=CH2), 5.46 (s, 1 H, ArCHO2), 5.23–5.16 (m, 2 H, H-1, CH2CH=CH2), 5.10 (d, 1 H, J = 10.4 Hz, CH2CH=CH2), 4.31 (dd, 1 H, J = 5.6, 13.2 Hz, CH2CH=CH2), 4.24 (dd, 1 H, J = 4.8, 10.8 Hz, H-6a), 4.14–4.07 (m, 2 H, CH2CH=CH2, H-3), 3.78 (s, 3 H, OCH3), 3.72 (t, 1 H, J = 10.6 Hz, H-6b), 3.58 (t, 1 H, J = 9.0 Hz, H-4), 3.50–3.44 (m, 1 H, H-5), 3.24–3.21 (m, 1 H, H-2), 1.95 (s, 3 H, CH3CONH), 1.62–1.57 (m, 1 H, SiC(CH3)2CH(CH3)2), 0.86 (s, 3 H, SiC(CH3)2CH(CH3)2), 0.85 (s, 3 H, SiC(CH3)2CH(CH3)2), 0.83 (s, 6 H, SiC(CH3)2CH(CH3)2), 0.13 (s, 3 H, SiCH3), 0.12 (s, 3 H, SiCH3); 13C NMR (100 MHz) δ 170.4, 160.2, 135.3, 130.2, 127.6, 117.1, 113.8, 101.3, 95.5, 82.7, 76.8, 73.5, 69.0, 66.2, 60.2, 55.5, 34.2, 25.0, 23.8, 20.2, 18.8, −1.6, −3.2. ESIMS m/z Calcd for C27H43NO7SiNa [M + Na+]: 544.2693. Found: 544.2693.

1.4. Dimethylthexylsilyl 2-Acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-β-d-glucopyranoside (4) and Dimethylthexylsilyl 2-Acetamido-3-O-allyl-2-deoxy-4-O-(4-methoxybenzyl)-β-d-glucopyranoside (5)

To a solution of 3 (1.59 g, 3.04 mmol), in anhydr DMF (22 mL) in the presence of 4Å MS was added NaBH3CN (1.91 g, 30.4 mmol) followed by a solution of TFA (4.70 mL, 61 mmol) in anhydr DMF (24 mL) at 0 °C over 25 min. After 1 h at 0 °C, the reaction mixture was warmed to room temperature and stirred for another 4 h. At this point the reaction mixture was poured into H2O (500 mL) and solid NaHCO3 was slowly added to neutralize the mixture to pH = 7.0. The water phase was extracted with CH2Cl2 (3 × 100 mL). The collected organic phase was washed with brine, dried over Na2SO4 and concentrated. The resulting residue was purified by flash chromatography on silica gel to afford 4 (1.11 g, 2.12 mmol, 70%) and 5 (90.5 mg, 0.17 mmol, 6%).

For 4 [α]d21 = −20.5 (c 0.8); 1H NMR (400 MHz) δ 7.23 (d, 2 H, J = 8.0 Hz, Ar-H), 6.85 (d, 1 H, J = 8.8 Hz, Ar-H), 5.92–5.83 (m, 1 H, CH2CH=CH2), 5.72 (d, 1 H, J = 7.2 Hz, CH3CONH), 5.24 (d, 1 H, J = 17.2 Hz, CH2CH=CH2), 5.13 (d, 1 H, J = 9.6 Hz, CH2CH=CH2), 5.02 (d, 1 H, J = 7.2 Hz, H-1), 4.53–4.46 (m, 2 H, ArCH2O), 4.24 (dd, 1 H, J = 5.6, 13.2 Hz, CH2CH=CH2), 4.15 (dd, 1 H, J = 6.0, 13.2 Hz, CH2CH=CH2), 3.85 (t, 1 H, J = 10.0 Hz, H-3), 3.79 (s, 3 H, OCH3), 3.69 (d, 2 H, J = 4.8 Hz, H-6a, H-6b), 3.56 (t, 1 H, J = 8.8 Hz, H-4), 3.51–3.46 (m, 1 H, H-5), 3.25–3.20 (m, 1 H, H-2), 3.08 (br. s, 1 H, OH), 1.94 (s, 3 H, CH3CONH), 1.63–1.56 (m, 1 H, SiC(CH3)2CH(CH3)2), 0.86 (s, 3 H, SiC(CH3)2CH(CH3)2), 0.84 (s, 3 H SiC(CH3)2CH(CH3)2), 0.82 (s, 6 H, SiC(CH3)2CH(CH3)2), 0.14 (s, 3 H, SiCH3), 0.11 (s, 3 H, SiCH3); 13C NMR (100 MHz) δ 170.4, 159.5, 135.4, 130.2, 129.5, 117.2, 114.0, 95.2, 80.6, 77.6, 74.0, 73.5, 73.2, 59.2, 55.5, 34.1, 25.0, 23.8, 20.1, 18.7, −1.6, −3.3. ESIMS m/z Calcd for C27H45NO7SiNa [M + Na+]: 546.2851. Found: 546.2863.

For 5 [α]d21 = +5.2 (c 0.6); 1H NMR (500 MHz) δ 7.23 (d, 2 H, J = 8.5 Hz, Ar-H), 6.85 (d, 1 H, J = 8.0 Hz, Ar-H), 5.92–5.86 (m, 1 H, CH2CH=CH2), 5.84 (d, 1 H, J = 8.5 Hz, CH3CONH), 5.24 (d, 1 H, J = 17.0 Hz, CH2CH=CH2), 5.14 (d, 1 H, J = 10.5 Hz, CH2CH=CH2), 5.02 (d, 1 H, J = 7.5 Hz, H-1), 4.73 (d, 1 H, J = 10.5 Hz, ArCH2O), 4.54 (d, 1 H, J = 11.0 Hz, ArCH2O), 4.28 (dd, 1 H, J = 5.0, 12.5 Hz, CH2CH=CH2), 4.14 (dd, 1 H, J = 6.0, 13.0 Hz, CH2CH=CH2), 3.93 (t, 1 H, J = 10.0 Hz, H-3), 3.78 (s, 4 H, OCH3, H-6a), 3.64–3.62 (m, 1 H, H-6b), 3.45 (t, 1 H, J = 9.5 Hz, H-4), 3.42–3.38 (m, 1 H, H-5), 3.30–3.25 (m, 1 H, H-2), 1.98 (s, 3 H, CH3CONH), 1.63–1.56 (m, 1 H, SiC(CH3)2CH(CH3)2), 0.86 (s, 3 H, SiC(CH3)2CH(CH3)2), 0.84 (s, 3 H, SiC(CH3)2CH(CH3)2), 0.82 (s, 6 H, SiC(CH3)2CH(CH3)2), 0.14 (s, 3 H, SiCH3), 0.10 (s, 3 H, SiCH3); 13C NMR (125 MHz) δ 170.4, 159.6, 135.3, 130.4, 129.9, 117.0, 114.1, 95.2, 80.8, 78.3, 75.2, 74.6, 73.7, 62.5, 59.6, 55.5, 34.2, 25.0, 23.8, 20.2, 18.7, −1.5, −3.2. ESIMS m/z Calcd for C27H45NO7SiNa [M + Na+]: 546.2863. Found: 546.2863

1.5. Dimethylthexylsilyl 2-Acetamido-4-O-acetyl-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-β-d-glucopyranoside (6)

To a solution of 4 (65.0 mg, 124 μmol) in anhydrous pyridine (1 mL) was added Ac2O (80.0 μL, 846 μmol). The resulting mixture was stirred for 4 h at room temperature under N2 atmosphere. The reaction was quenched with MeOH and the volatiles were removed under reduced pressure. The residue was dissolved in CH2Cl2 and washed with 0.1 N HCl, satd. NaHCO3 and brine. The organic phase was dried over Na2SO4 and concentrated. The residue was subjected to silica gel column chromatography (EtOAc–hexane 2:3) to afford acetate 6 (63.9 mg, 113 μmol, 91%) as a syrup. [α]d22 = +15.1 (c 1.1); 1H NMR (500 MHz) δ 7.22 (d, 2 H, J = 8.5 Hz, Ar-H), 6.84 (d, 2 H, J = 9.0 Hz, Ar-H), 5.82–5.74 (m, 2 H, CH3CONH, CH2CH=CH2), 5.21–5.15 (m, 2 H, H-1, CH2CH=CH2), 5.10 (dd, 1 H, J = 1.5, 10.5 Hz, CH2CH=CH2), 4.89 (t, 1 H, J = 9.5 Hz, H-4), 4.43 (s, 2 H, Ar-CH2), 4.17 (t, 1 H, J = 9.5 Hz, H-3), 4.06–4.04 (m, 2 H, CH2CH=CH2), 3.78 (s, 3 H, OCH3), 3.63–3.59 (m, 1 H, H-5), 3.49–3.48 (m, 2 H, H-6a, H-6b), 3.14–3.09 (m, 1 H, H-2), 1.96 (s, 3 H, CH3COO), 1.94 (s, 3 H, CH3CONH), 1.64–1.58 (m, 1 H, SiC(CH3)2CH(CH3)2), 0.86 (d, 3 H, J = 2.0 Hz, SiC(CH3)2CH(CH3)2), 0.85 (d, 3 H, J = 2.0 Hz, SiC(CH3)2CH(CH3)2), 0.83 (s, 3 H, SiC(CH3)2CH(CH3)2), 0.82 (s, 3 H, SiC(CH3)2CH(CH3)2), 0.16 (s, 3 H, SiCH3), 0.12 (s, 3 H, SiCH3); 13C NMR (125 MHz) δ 170.5, 170.0, 159.4, 134.9, 130.4, 129.5, 116.9, 113.9, 94.6, 77.8, 73.3, 72.8, 72.1, 69.9, 60.2, 55.5, 34.3, 25.0, 23.8, 21.2, 20.3, 18.8, −1.6, −3.3. ESIMS m/z Calcd for C29H47NO8SiNa [M + Na+]: 588.2969. Found: 588.2970

1.6. Dimethylthexylsilyl 2-Acetamido-6-O-acetyl-3-O-allyl-2-deoxy-4-O-(4-methoxybenzyl)-β-d-glucopyranoside (7)

Following a similar protocol for 6, 5 (87.2 mg, 166 μmol) was allowed to react with Ac2O (100 μL, 1.1 mmol) in pyridine (1 mL) to furnish 7 (78.0 mg, 138 μmol, 83%) as a syrup. [α]d22 = +20.8 (c 1.1); 1H NMR (500 MHz) δ 7.22 (d, 2 H, J = 8.5 Hz, Ar-H), 6.85 (d, 2 H, J = 8.5 Hz, Ar-H), 5.94–5.86 (m, 1 H, CH2CH=CH2), 5.80–5.76 (m, 1 H, CH3CONH), 5.25 (dd, 1 H, J = 1.5, 17.5 Hz, CH2CH=CH2), 5.14 (d, 1 H, J = 10.5 Hz, CH2CH=CH2), 4.97 (d, 1 H, J = 8.0 Hz, H-1), 4.73 (d, 1 H, J = 10.5 Hz, Ar-CH2), 4.48 (d, 1 H, J = 10.5 Hz, ArCH2), 4.30–4.25 (m, 2 H, CH2CH=CH2, H-6a), 4.17–4.10 (m, 2 H, CH2CH=CH2, H-6b), 3.95 (t, 1 H, J = 9.5 Hz, H-3), 3.78 (s, 3 H, OCH3), 3.54–3.51 (m, 1 H, H-5), 3.38 (t, 1 H, J = 9.0 Hz, H-4), 3.31–3.26 (m, 1 H, H-2), 2.01 (s, 3 H, CH3COO), 1.94 (s, 3 H, CH3CONH), 1.61–1.56 (m, 1 H, SiC(CH3)2CH(CH3)2), 0.85 (d, 3 H, J = 1.5 Hz, SiC(CH3)2CH(CH3)2), 0.83 (d, 3 H, 1.0 Hz, SiC(CH3)2CH(CH3)2), 0.81 (s, 3 H, SiC(CH3)2CH(CH3)2), 0.80 (s, 3 H, SiC(CH3)2CH(CH3)2), 0.11 (s, 3 H, SiCH3), 0.10 (s, 3 H, SiCH3); 13C NMR (125 MHz) δ 171.0, 170.3, 159.6, 135.2, 130.1, 130.0, 117.1, 114.1, 95.0, 80.8, 78.2, 74.4, 73.7, 73.0, 63.6, 59.5, 55.5, 34.3, 25.0, 23.8, 21.0, 20.3, 20.2, 18.7, −1.7, −3.3. ESIMS m/z Calcd for C29H47NO8SiNa [M + Na+]: 588.2969. Found: 588.2967

1.7. Dimethylthexylsilyl 2-O-Benzoyl-3,4,6-tri-O-benzyl-β-d-glucopyranosyl-(1→4)-2-acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-β-d-glucopyranoside (9)

A solution of 4 (253 mg, 483 μmol) in CH2Cl2 (15 mL) was stirred for 2 h in the presence of 5Å MS (820 mg) at ambient temperature under N2 atmosphere after which TMSOTf (48 μL, 265 μmol) was added followed by a solution of 89 (605.8 mg, 867 mmol) in CH2Cl2 (8 mL) over 1.5 h. The mixture was stirred for another 2.5 h until TLC (EtOAc–hexane 2:3) showed that the reactant was completely consumed. The reaction mixture was diluted with CH2Cl2 and the solid was filtered off. The filtrate was washed with satd. aq NaHCO3 and brine. The collected organic phase was dried over Na2SO4 and concentrated. The resulting residue was purified by flash chromatography (EtOAc–hexane 2:5) on silica gel to afford disaccharide 9 (260.0 mg, 245 μmol, 51%). [α]d21 = +13.1 (c 0.8); 1H NMR (500 MHz) δ 7.97 (d, 2 H, J = 7.5 Hz, Ar-H), 7.58 (t, 1 H, J = 7.5 Hz, Ar-H), 7.46–7.57 (t, 2 H, J = 8.0 Hz, Ar-H), 7.38–7.11 (m, 17 H, Ar-H), 6.88 (d, 2 H, J = 8.5 Hz, Ar-H), 5.88–5.82 (m, 2 H, CH3CONH, CH2CH=CH2), 5.24–5.18 (m, 2 H, H”-2, CH2CH=CH2), 5.05 (d, 1 H, J = 10.5 Hz, CH2CH=CH2), 4.81 (d, 1 H, J = 10.5 Hz, ArCH2), 4.76 (d, 1 H, J = 6.5 Hz, H’-1), 4.74 (d, 1 H, J = 11.5 Hz, ArCH2), 4.66–4.52 (m, 6 H, H”-1, ArCH2), 4.31 (d, 1 H, J = 11.5 Hz, ArCH2), 4.28 (dd, 1 H, J = 5.0, 13.0 Hz, CH2CH=CH2), 4.11 (dd, 1 H, J = 5.5, 13.0 Hz, CH2CH=CH2) 3.96 (t, 1 H, J = 7.0 Hz, H’-3), 3.83–3.69 (m, 8 H, OCH3, H’-4, H’-6a, H’-6b, H”-6a, H”-6b), 3.58–3.53 (m, 3 H, H”-3, H”-4, H’-5), 3.46–3.42 (m, 1 H, H”-5), 3.41–3.38 (m, 1 H, H’-2), 1.99 (s, 3 H, CH3CONH), 1.59–1.54 (m, 1 H, SiC(CH3)2CH(CH3)2), 0.84 (d, 3 H, J = 2.5 Hz, SiC(CH3)2CH(CH3)2), 0.82 (d, 3 H, J = 2.5 Hz, SiC(CH3)2CH(CH3)2), 0.78 (s, 3 H, SiC(CH3)2CH(CH3)2), 0.77 (s, 3 H, SiC(CH3)2CH(CH3)2), 0.03 (s, 3 H, SiCH3), −0.02 (s, 3 H, SiCH3); 13C NMR (125 MHz, CDCl3) δ 170.1, 165.6, 159.5, 138.4, 138.3, 138.1, 135.6, 133.5, 130.6, 130.0, 129.8, 128.7, 128.6, 128.5, 128.2, 128.1, 128.0, 127.8, 116.5, 114.1, 99.9 (C1”, JC1”-H1” = 163.4), 95.2 (C1’, J C1’-H1’ = 164.2), 83.1, 78.3, 78.2, 75.4, 75.2, 74.6, 74.4, 73.8, 73.3, 72.6, 68.9, 68.8, 56.5, 55.4, 34.2, 25.0, 23.7, 20.3, 18.8, −1.8, −3.4. ESIMS m/z Calcd for C61H77NO13SiNa [M + Na+]: 1082.5062. Found: 1082.5066.

1.8. Dimethylthexylsilyl 3,4,6-Tri-O-benzyl-β-d-glucopyranosyl-(1→)-2-acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-β-d-glucopyranoside (10)

To a solution of 9 (160.0 mg, 151 μmol) in MeOH–THF (1:1, v:v, 6 mL) was added a solution of NaOMe in MeOH (25 wt%, 150 μL, 656 μmol). The resultant mixture was stirred for 18 h at ambient temperature under N2 atmosphere. Monitoring by TLC (MeOH–CH2Cl2 1:4) indicated that the reaction went to completion. The reaction was neutralized with Amberlite IR-120 resin (H+), filtered and the filtrate was concentrated. The residue was purified by flash chromatography on silica gel (EtOAc–CH2Cl2 1:5) to furnish alcohol 10 (110.5 mg, 116 μmol, 77%). [α]d21 = +17.5 (c 1.3); 1H NMR (500 MHz) δ 7.39–7.27 (m, 15 H, Ar-H), 7.17 (d, 2 H, J = 7.5 Hz, Ar-H), 6.87 (d, 2 H, J = 9.0 Hz, Ar-H), 5.88–5.81 (m, 1 H, CH2CH=CH2), 5.75 (d, 1 H, J = 7.5 Hz, CH3CONH), 5.19 (d, 1 H, J = 12.5 Hz, CH2CH=CH2), 5.06–5.03 (m, 2 H, CH2CH=CH2, H’-1), 4.94 (d, 1 H, J = 11.5 Hz, ArCH2), 4.84–4.80 (m, 2 H, ArCH2), 4.62 (d, 1 H, J = 12.0 Hz, ArCH2), 4.58–4.47 (m, 5 H, ArCH2, H”-1), 4.45 (dd, 1 H, J = 5.0, 12.5 Hz, CH2CH=CH2), 4.08–4.02 (m, 2 H, CH2CH=CH2, H’-3), 3.96–3.91 (m, 2 H, H’-4, H’-6a), 3.76 (s, 3 H, OCH3), 3.70–3.66 (m, 3 H, H’-6b, H”-6a, H”-6b), 3.63–3.59 (m, 2 H, H”-4, OH), 3.52–3.45 (m, 3 H, H”-2, H”-3, H’-5), 3.42–3.39 (m, 1 H, H”-5), 3.25–3.20 (m, 1 H, H’-2), 1.94 (s, 3 H, CH3CONH), 1.65–160 (m, 1 H, SiC(CH3)2CH(CH3)2), 0.88 (d, 3 H, J = 2.5 Hz, SiC(CH3)2CH(CH3)2), 0.87 (d, 3 H, J = 2.5 Hz, SiC(CH3)2CH(CH3)2), 0.84 (s, 3 H, SiC(CH3)2CH(CH3)2), 0.83 (s, 3 H, SiC(CH3)2CH(CH3)2), 0.16 (s, 3 H, SiCH3), 0.12 (s, 3 H, SiCH3); 13C NMR (125 MHz) δ 170.3, 159.5, 139.1, 138.5, 138.4, 135.7, 129.9, 128.6, 128.5, 128.2, 128.1, 128.0, 127.9, 127.8, 116.2, 114.0, 103.4 (C1”, JC1”-H1” = 165.7), 95.0 (C1’, J C1’-H1’ = 164.1), 84.8, 79.5, 77.7, 76.1, 75.3, 75.2, 74.4, 73.7, 73.6, 73.3, 69.1, 68.9, 59.1, 55.4, 34.3, 25.0, 23.8, 20.3, 18.8, −1.6, −3.2. ESIMS m/z Calcd for C54H73NO12SiNa [M + Na+]: 978.4800. Found: 978.4823

1.9. Dimethylthexylsilyl 3,4,6-Tri-O-benzyl-β-d-mannopyranosyl-(1→)-2-acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-β-d-glucopyranoside (11)

To a solution of 10 (110.5 mg, 116 μmol) in CH2Cl2 (6 mL) was added Dess-Martin periodinane (97 mg, 229 μmol). The resulting mixture was stirred for 2 h at ambient temperature under N2 temperature. Monitoring by TLC (EtOAc–hexane 1:1) showed the reaction went to completion. The mixture was diluted with CH2Cl2, washed with aq NaHCO3 containing Na2S2O3 and brine. The organic phase was dried over Na2SO4 and concentrated. The resulting residue was dissolved in MeOH–CH2Cl2 (1:1, v:v, 6 mL). The solution was cooled to 0 °C, and NaBH4 (58 mg, 1.5 mmol) was added. The resulting mixture was stirred for 12 h while the temperature was elevated to the ambient. TLC (EtOAc–CH2Cl2 1:1) showed that the reaction went to completion. The reaction was quenched with AcOH and concentrated. The residue was diluted with CH2Cl2 and washed with brine. The organic phase was dried over Na2SO4 and concentrated. The residue was applied to silica gel column (EtOAc–CH2Cl2 1:2) to afford 11 (92.3 mg, 97 μmol, 84%) and 10 (5.0 mg, 5.2 μmol, 4.5%).

11: [α]d21 = +2.8 (c 1.0); 1H NMR (500 MHz) δ 7.36–7.20 (m, 17 H, Ar-H), 6.85 (d, 2 H, J = 8.5 Hz, Ar-H), 5.94 (d, 1 H, J = 8.0 Hz, CH3CONH), 5.87–5.81 (m, 1 H, CH2=CHCH2), 5.19 (d, 1 H, J = 12.5 Hz, CH2=CHCH2), 5.05 (d, 1 H, J = 10.0 Hz, CH2=CHCH2), 5.02 (d, 1 H, J = 6.5 Hz, H’-1), 4.86 (d, 1 H, J = 11.0 Hz, ArCH2), 4.67 (d, 1 H, J = 12.0 Hz, ArCH2), 4.61 (s, 1 H, H”-1), 4.58–4.51 (m, 5 H, ArCH2), 4.43 (d, 1 H, J = 11.5 Hz, ArCH2), 4.28 (dd, 1 H, J = 5.5, 12.5 Hz, CH2=CHCH2), 4.10 (dd, 1 H, J = 6.0, 12.5 Hz, CH2=CHCH2), 4.03 (d, 1 H, J = 3.0 Hz, H”-2), 3.99 (t, 1 H, J = 8.0 Hz, H’-3), 3.93 (t, 1 H, J = 8.0 Hz, H’-4), 3.87 (t, 1 H, J = 9.5 Hz, H”-4), 3.77–3.69 (m, 7 H, OCH3, H’-6a, H’-6b, H”-6a, H”-6b), 3.60–3.57 (m, 1 H, H’-5), 3.47–3.42 (m, 2 H, H’-2, H”-3), 3.36–3.33 (m, 1 H, H”-5), 2.60 (br. s, 1 H, OH), 1.94 (s, 3 H, CH3CONH), 1.66–1.60 (m, 1 H, SiC(CH3)2CH(CH3)2), 0.87 (d, 3 H, J = 2.5 Hz, SiC(CH3)2CH(CH3)2), 0.86 (d, 3 H, J = 2.5 Hz, SiC(CH3)2CH(CH3)2), 0.84 (s, 6 H, SiC(CH3)2CH(CH3)2), 0.15 (s, 3 H, SiCH3), 0.13 (s, 3 H, SiCH3); 13C NMR (125 MHz) δ 170.2, 159.4, 138.5, 138.4, 135.6, 130.4, 129.6, 128.7, 128.6, 128.5, 128.3, 128.1, 127.9, 127.7, 116.6, 114.1, 100.0 (C1”, JC1”-H1” = 160.6), 95.0 (C1’, J C1’-H1’ = 165.0), 81.9, 78.6, 76.0, 75.6, 75.4, 74.7, 74.3, 73.7, 73.4, 73.0, 71.6, 69.4, 68.1, 57.8, 55.4, 34.3, 25.0, 23.8, 20.3, 18.8, −1.7, −3.2. ESIMS m/z Calcd for C54H73NO12SiNa [M + Na+]: 978.4800. Found: 978.4818

1.10. Dimethylthexylsilyl 2-O-(Benzylsulfonyl)-3,4,6-tri-O-benzyl-β-d-mannopyranosyl-(1→)-2-acetamido-3-O-allyl-O-2-deoxy-6-O-(4-methoxybenzyl)-β-d-glucopyranoside (12)

To a solution of 11 (89.0 mg, 93 μmol) in pyridine (2 mL) was added benzylsulfonyl chloride (31.0 mg, 162 μmol) at 0 °C under N2 atmosphere. After stirring 7 h, TLC (EtOAc–hexane 1:1) showed that the reaction went to completion. The reaction was diluted with CH2Cl2, washed with 0.1 N HCl, satd. NaHCO3 and brine. The combined organic phase was dried over Na2SO4 and concentrated. The residue was purified by flash chromatography on silica gel (EtOAc–hexane 2:3) to afford sulfonate 12 (100 mg, 90 μmol, 97%) as a syrup. [α]d22 = −43.6 (c 0.8); 1H NMR (500 MHz) δ 7.42–7.26 (m, 22 H, Ar-H), 6.85 (d, 2 H, J = 9.0 Hz, Ar-H), 5.93 (d, 1 H, J = 8.5 Hz, CH3CONH), 5.84–5.78 (m, 1 H, CH2=CHCH2), 5.17 (d, 1 H, J = 17.0 Hz, CH2=CHCH2), 5.11 (d, 1 H, J = 2.0 Hz, H”-2), 5.03 (d, 1 H, J = 10.5 Hz, CH2=CHCH2), 4.93 (d, 1 H, J = 7.5 Hz, H’-1), 4.90 (d, 1 H, J = 10.5 Hz, ArCH2), 4.76 (d, 1 H, J = 11.0 Hz, ArCH2), 4.63–4.49 (m, 6 H, ArCH2, H”-1), 4.43 (d, 1 H, J = 12.0 Hz, ArCH2), 4.38 (s, 2 H, ArCH2SO2), 4.22 (dd, 1 H, J = 5.0, 13.0 Hz, CH2=CHCH2), 4.13 (dd, 1 H, J = 5.5, 13.0 Hz, CH2=CHCH2), 3.97 (t, 1 H, J = 6.0 Hz, H’-3), 3.81–3.65 (m, 11 H, OCH3, H’-2, H’-4, H’-5, H’-6a, H’-6b, H”-4, H”-6a, H”-6b), 3.53–3.50 (dd, 1 H, J = 3.0, 9.5 Hz, H”-3), 3.34–3.32 (m, 1 H, H”-5) 1.80 (s, 3 H, CH3CONH), 1.64–1.60 (m, 1 H, SiC(CH3)2CH(CH3)2), 0.88–0.84 (m, 12 H, SiC(CH3)2CH(CH3)2), 0.15 (s, 3 H, SiCH3), 0.14 (s, 3 H, SiCH3); 13C NMR (125 MHz) δ 170.1, 159.5, 138.5, 138.3, 137.4, 135.7, 131.1, 130.5, 129.7, 129.0, 128.9, 128.8, 128.7, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 127.8, 116.4, 114.1, 98.3 (C1”, JC1”-H1” = 160.4), 95.3 (C1’, J C1’-H1’ = 163.4), 80.3, 79.0, 77.8, 75.9, 75.6, 75.5, 74.3, 73.8, 73.4, 72.8, 72.1, 69.8, 69.1, 57.9, 56.6, 55.4, 34.3, 25.0, 23.4, 20.3, 18.8, −1.7, −3.2. ESIMS m/z Calcd for C61H79NO14SiNa [M + Na+]: 1132.4888. Found: 1132.4905.

Supplementary Material

01

Acknowledgments

We thank the NIH (GM62160) for support of this work.

Footnotes

*

Supplementary data is available for this Note

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