6R- and 6S-6C-Methylmannose from D-mannuronolactone.: Inhibition of phosphoglucomutase and phosphomannomutase:: agents for the study of the primary metabolism of mannose

The syntheses of 6S-3 and 6R-6 6C-methylmannoses rely on opposite and highly stereoselective reductions of fully and partially protected ketones derived from D-mannuronolactone, respectively. Reduction of the silylated ketone 2 by sodium borohydride was accompanied by complete migration of the silyl protecting group to the new stereogenic centre; the silyl migration was suppressed when the reduction was conducted in the presence of cerium(III) chloride. Both epimers were good inhibitors of phosphoglucomutase and phosphomannomutase, and are specific inhibitors of phosphohexomutases, This work confirms that 6C-alkylhexoses provide a valuable set of compounds with good bioavailability for the study of enzymes involved in the primary metabolism of sugar phosphates. The X-ray crystallographic analysis of 7-deoxy-2,3:5,6-di-O-isopropylidene-alpha-L-glycero-D-manno-heptofuranose 16 is reported. (C) 1999 Elsevier Science Ltd. All rights reserved.