Reaction Steps
To a solution of commercially available L-ascorbic acid 163 (30.0 g, 0.17 mmol) in distilled water (200 mL), palladium on activated carbon (10%, 1.0 g) was added as a catalyst at RT. The reaction mixture was placed in a steel reaction vessel and underwent hydrogenation (100 psi) at 60° C. for 48 h. The progress of the reaction was followed by TLC analysis of aliquots (EtOAc: MeOH: H2O=10:3:1). When the starting material 163 had been essentially consumed, the reaction was stopped and the reaction mixture was filtered under vacuum, and washed with water (2×50 mL). The filtrate and the wash were combined and the water was then evaporated under reduced pressure. The residue was recrystallized from methanol-ethyl acetate to give compound 164 as a white solid (21.5 g, 71%). The NMR spectrum of compound 164 matched that of the published.105 To a suspension of the lactone 164 (10.0 g, 56.1 mmol) in dry acetone (200 mL), 2,2-dimethoxypropane (40 mL, 0.32 mmol) was added at RT. To this mixture, p-toluenesulfonic acid (200 mg) was added as a catalyst. The progress of the reaction was followed by TLC analysis of aliquots (Hexane:EtOAc, 1:1). When the starting material 164 had been essentially consumed, the reaction was stopped by addition of triethylamine (1 mL). The solvent was then evaporated under reduced pressure, and the residue was purified by column chromatography (Hexane:EtOAc, 1:1) to give compound 165 as a white solid. The NMR spectrum of compound 164 matched that of the published data.105 The lactone 165 (5.0 g, 19.3 mmol) was dissolved in THF (20 mL), and MeOH (50 mL) was then added. To this solution, NaBH4 was added portionwise at 0° C. The progress of the reaction was followed by TLC analysis of aliquots (Hexane:EtOAc, 1:1). When the starting material 165 had been consumed, the solvent was evaporated under reduced pressure. The residue was redissolved in EtOAc (50 mL), washed with aqueous tartaric acid solution (2×10 mL), brine (50 mL), and dried over Na2SO4. After evaporating the solvent, the crude diol was used directly in the next step. The crude diol was dissolved in CH2Cl2 (50 mL), and the solution was added dropwise to a mixture of pyridine (100 mL) and methanesulfonyl chloride (6 mL, 77.5 mmol) cooled to 0° C. The reaction mixture was stirred at 0° C. for 30 min, then allowed to warm to room temperature for 6 h. When TLC analysis of aliquots (Hexane:EtOAc, 1:1) showed total consumption of the starting material, the reaction mixture was poured into ice water, extracted with CH2Cl2 (3×100 mL), washed with brine (50 mL), and dried over Na2SO4. Purification by column chromatography (Hexane:EtOAc, 2:1) yielded compound 166 as a colorless syrup (3.6 g, 45% o for two steps). [α]22D +54 (c 4, CH2Cl2); 1H NMR ((CD3)2O) δ: 4.87 (dd, 1H, J3,4=6.1, J4,5=4.8, H-4), 4.57 (ddd, 1H, J1b,2=6.0, J1a,1b=12.0, H-1b), 4.56-4.48 (m, 3H, H-2, H-3, H-1a), 4.45 (ddd, 1H, H-5), 4.13 (dd, 1H, J5,6b=6.7, J6a,6b=8.6, H-6b), 4.03 (dd, 1H, J5,6a=6.6, H-6a), 3.24, and 3.15 (2 s, 6H, 2×OSO2CH3), 1.52, 1.41, 1.38, and 1.34 (4 s, 12H, 4×CH3). 13C NMR ((CD3)2O) δ: 114.3, 113.8 ((CH3)2C(OR)2), 83.3 (C-4), 79.7 (C-3), 79.0 (C-2), 78.9 (C-1), 72.9 (C-5), 69.6 (C-6), 43.0, 40.9 (2×OSO2CH3), 31.3, 29.9, 29.3, and 29.2 (4×CH3). Anal. Calcd. for C14H26O10S2: C, 40.18; H, 6.26. Found: C, 39.89; H, 6.02.
