6R-, and 6S, -6C-methylglucose from D-glucuronolactone: Efficient synthesis of a seven carbon fucose analogue: Inhibition of some enzymes of primary metabolism

Syntheses of the two epimeric 6C-methylglucoses from D-glucuronolactone rely on a nonstereoselective reduction of an intermediate lactol. A highly stereoselective reduction of a silylated lactol, which is accompanied by a silyl migration, gives easy access to 6S-6C-methylglucose-a seven carbon fucose analogue-in five steps from glucuronolactone in an overall yield of 40%. An azido analogue of 6R-6C-methylglucose is also reported. Such compounds may provide new materials for the selective inhibition of various enzymes of primary metabolism including glucokinase, glucose-6-phosphatase, and phosphoglucomutase. X-ray crystal structures of(IS,3R,4S,5S,7R,8R)-3-methyl-7,8-O-isopropylidene-3,4,7,8-tetrahydroxy-2,6-dioxabicyclo[3,3,0]octane and 7-deoxy-1,2-5,6-di-O-isopropylidene-L-glycero-alpha-D-gluco-heptofuranose are reported. (C) 1997 Elsevier Science Ltd.