Potential glycosidase inhibitors: synthesis of 1,4-dideoxy-1,4-imino derivatives of D-glucitol, D- and L-xylitol, D- and L-allitol, D- and L-talitol, and D-gulitol

Abstract

Conversion of 2,3,5,6-tetra-O-benzyl-D-galactofuranose (19) into its oxime and subsequent treatment with methanesulphonyl chloride gave 2,3,5,6-tetra-O-benzyl-4-O-methylsulphonyl-D-galactonitrile (21). Reductive cyclization by sodium borohydride/cobalt(II) chloride, followed by hydrogenolysis under acidic conditions yielded 1,4-dideoxy-1,4-imino-D-glucitol hydrochloride (11). A similar reaction sequence was used to convert 2,3,5-tri-O-benzyl L-arabinofuranose (23)via the nitrile (25) into 1,4-dideoxy-1,4-imino-D-xylitol hydrochloride (12), and the corresponding D-arabinose derivative (27) gave 1,4-dideoxy-1,4-imino-L-xylitol hydrochloride (13), using the same chemistry.Treatment of 2,3 : 5,6-di-O-isopropylidene-β-D-gulofuranose (31) with hydroxylamine and then methanesulphonyl chloride in pyridine gave 4-O-methylsulphonyl-2,3 : 5,6-di-O-isopropylidene-D-gulononitrile (32), which was converted by treatment with lithium aluminium hydride and subsequent acid hydrolysis into 1,4-dideoxy-1,4-imino-D-allitol hydrochloride (14); similar chemistry in the enantiomeric series gave the L-allitol derivative (15). An analogous reaction sequence was used to convert 2,3 : 5,6-di-O-isopropylidene-α-D-mannofuranose into 4-O-methylsulphonyl-2,3 : 5,6-di-O-isopropylidene D-mannononitrile (38) and thence into 1,4-dideoxy-1,4-imino-D-talitol hydrochloride (16); L-mannonolactone was converted via 2,3 : 5,6-di-O-isopropylidene-α-L-mannofuranose (41) into 1,4-dideoxy-1,4-imino-L-talitol hydrochloride (17).2,3 : 5,6-Di-O-isopropylidene-β-D-allofuranose (45) was converted via its oxime (46) into 4-O-methylsulphonyl-2,3 : 5,6-di-O-isopropylidene-D-allononitrile (47), which on reductive cyclization with lithium aluminium hydride, and subsequent acid hydrolysis, gave 1,4-dideoxy-1,4-imino-D-gulitol hydrochloride (18).