Straightforward synthesis of thiodisaccharides by ring-opening of sugar epoxides

MANZANO, V. E.; UHRIG, M. L.; VARELA, O.

JOURNAL OF ORGANIC CHEMISTRY

American Chemical Society Publications

Lugar: Columbus, USA; Año: 2008 p. 7224 - 7235

0022-3263

3,4-Anhydro hexopyranosides have been prepared by diastereoselective epoxidation of derivatives of 2-propyl 3,4-dideoxy-R-D-erythro-hex-3-enopyranoside (5), selectively protected at HO-2 and HO-6. The allylic group at C-2, in 5 and derivatives, plays a critical role in the facial selectivity of the epoxidation reaction. Thus, the free HO-2 in 3 (the 6-O-acetyl derivative of 5) directs the attack of m-chloroperbenzoic acid from the more hindered R face of the molecule to give 2-propyl 6-O-acetyl-3,4-anhydro-R-D-allopyranoside (7) accompanied by the epoxide 6 as a very minor product. Reverse diastereoselectivity has been obtained when the HO-2 in 3 was substituted by a bulky tert-butyldimethylsilyl (TBS) group. In this case, the major isomer was the 2-O-TBS derivative of 6 (R-D-galacto configuration). The ring-opening of sugar epoxides by nucleophilic per-O-acetyl-1-thio--D-glucopyranose (11) was employed as a convenient approach to the synthesis of (1-3)- and (1-4)-thiodisaccharides. For example, ring-opening of the oxirane 7 by 11 led to the expected regioisomeric per-O-acetyl thiodisaccharides -D-Glc-S-(1-3)-4-thio-R-D-Glc-O-iPr (12) and -D-Glc-S-(1-4)-4-thio-RD-Gul-O-iPr (13). Regioselectivity in the construction of the (1-4)-thioglycosidic linkage could be achieved by hindering C-3 of the 3,4-anhydro sugar with a bulky silyloxy group at the vicinal C-2. For instance, coupling of the 2-O-TBS derivative of 7 with 11 led regioselectively to the protected thiodisaccharide -D-Glc-S- (1-4)-4-thio-R-D-Glc-O-iPr (27). The utility of the approach was demonstrated through the synthesis of sulfur linked analogues of naturally occurring (laminarabiose and cellobiose) and non-natural disaccharides (i.e., -D-Glc-(1-4)-R-D-Gul).