Syntheses of 6-deoxy-3-O-methyl-D-gulose and 6-deoxy-3-O-methyl-L-mannose(L-acofriose)

Abstract

A new and convenient synthesis of 6-deoxy-3-O-methyl-D-gulose (16) has been achieved by a route involving methylation and partial hydrolysis of 1,2 : 5,6-di-O-isopropylidene-α-D-gulofuranose (9) with acid to give 1,2-O-isopropylidene-3-O-methyl-α-D-gulofuranose (11). The diol (11) was converted into 6-deoxy-3-O-methyl-D-gulose (16) by ring-opening of the derived epoxide (14) with lithium aluminium hydride followed by hydrolysis with acid of the 6-deoxy-1,2-O-isopropylidene-3-O-methyl-α-D-gulofuranose (15) so formed. L-Acofriose (6-deoxy-3-O-methyl-L-mannose)(25), a sugar found in certain cardiac glycosides, has been synthesised for the first time. Treatment of either 6-O-benzoyl-1,2-O-isopropylidene-3-O-methyl-5-O-methyl-sulphonyl-α-D-gulofuranose (21) or the debenzoylated compound (22) with sodium methoxide afforded 5,6-an-hydro-1,2-O-isopropylidene-3-O-methyl-β-L-mannofuranose (23), which yielded L-acofriose (25) on reductive ring-opening and hydrolysis with acid. Attempts to obtain entry into the L-mannose series by means of a benzoate displacement reaction on the 6-deoxy-1,2-O-isopropylidene-3-O-methyl-α-D-gulofuranose 5-sulphonates (17) and (18) were unsuccessful.