反应详情

BF3.Et2O (7.7 mL, 60.7 mmol) was added dropwise over the course of 15 minutes to a solution of 1,2,3,4,6-penta-O-acetyl-α,β-D-mannose (5d) (See FIG. 7) (4.7 g, 12.1 mmol) and Br(CH2)2OH (1.05 mL, 14.8 mmol) in CH2Cl2 (22 mL) at 0° C. under N2. After 1 hour, the solution was warmed to room temperature. After 25 hours, the reaction solution was added to ice water (20 mL) and extracted with CH2Cl2 (20 mL×2). These extracts were combined, washed with water (20 mL), sat. NaHCO3 (aq., 20 mL), water (20 mL), dried (MgSO4), filtered, and the solvent removed. The residue was crystallized from EtOAc/iso-octane to give 2-bromoethyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside (4i) (See FIG. 7) (3.52 g, 64%). Purification of the resulting mother liquor by flash chromatography (EtOAc:hexane, 1:3) gave further 4i (See FIG. 7) (320 mg, 6%; 70% in total) as a white highly crystalline solid; mp 121-123° C. [lit., (Dahmén et al., “2-Bromoethyl Glycosides—Synthesis and Characterization,” Carbohydr. Res., 116:303-307 (1983), which is hereby incorporated by reference) 118-119° C. (EtOAc/iso-octane)]; [α]28D=+48.3 (c 1.31, CHCl3) [lit., (Dahmén et al., “2-Bromoethyl Glycosides—Synthesis and Characterization,” Carbohydr. Res., 116:303-307 (1983), which is hereby incorporated by reference) [α]23D=+45 (c 0.6, CDCl3)]; 1H NMR (200 MHz, CDCl3) δ 1.99, 2.05, 2.10, 2.16 (s×4, 3H×4, Ac×4), 3.52 (t, J6 Hz, 2H, —CH2Br), 3.82-4.04 (m, 2H, —OCH2—), 4.09-4.16 (m, 1H, H-5), 4.13 (dd, J5,6 2 Hz, J6,6′ 12 Hz, 1H, H-6) 4.28 (dd, J5,6′ 6 Hz, J6,6′ 12 Hz, 1H, H-6′), 4.87 (br s, 1H, H-1), 5.22-5.40 (m, 3H, H-2, H-3, H-4). NaSSO2CH3 (230 mg, 1.72 mmol) was added to a solution of 4i (See FIG. 7) (600 mg, 1.32 mmol) in DMF (17 mL) under N2 and warmed to 55° C. After 20 hours, the solution was cooled and the solvent removed. The residue was purified by flash chromatography (EtOAc:hexane, 9:11) and the resulting solid recrystallized from Et2O/hexane to give 1i (See FIG. 7) (566 mg, 88%) as a white solid; mp 128-129° C. (Et2O/hexane); [α]27D=+53.2 (c 0.92, CHCl3); IR (KBr) 1739 cm−1 (C═O), 1325, 1129 cm−1 (S—SO2); 1H NMR (500 MHz, CDCl3, COSY) δ 1.97, 2.04, 2.09, 2.14 (s×4, 3H×4, Ac×4), 3.37-3.40 (m, 2H, -CH2S—), 3.38 (s, 3H, CH3SO2—), 3.79 (dt, Jd 10.5 Hz, Jt 5.8 Hz, 1H, —OCHH′—), 3.98-4.03 (m, 2H, —OCHH′—, H-5), 4.09 (dd, J5,6 2.5 Hz, J6,6′ 12.5 Hz, 1H, H-6), 4.26 (dd, J5,6′ 5.6 Hz, J6,6′ 12.5 Hz, 1H, H-6′), 4.85 (d, J1,2 0.7 Hz, 1H, H-1), 5.23-5.29 (m, 3H, H-2, H-3, H-4); 13C NMR (50 MHz, CDCl3) δ 20.6, 20.7, 20.8 (CH3COO—×4), 35.7, (—CH2S—),50.8 (CH3SO2—), 62.5 (—OCH2—), 66.0, 66.8, 69.0, 69.2, 69.3 (C-2, C-3, C-4, C-5, C-6), 97.7 (C-1), 169.7, 169.9, 170.0, 170.6 (CH3COO—×4); HRMS m/z (FAB+): Found 487.0954 (M+H−); C17H27O12S2 requires 487.0944.

1. waitAfter 25 hours
2. extractionextracted with CH2Cl2 (20 mL×2)
3. washwashed with water (20 mL), sat. NaHCO3 (aq., 20 mL), water (20 mL)
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. customthe solvent removed
7. customThe residue was crystallized from EtOAc/iso-octane