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

J. Grant Buchanan, Keith W. Lumbard, Robert J. Sturgeon, Deryk K. Thompson, Richard H. Wightman

Research output: Contribution to journalArticle

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-ß- D-gulofuranose (31) with hydroxylamine and then methanesulphonyl chloride in pyridine gave 4-O-methvlsulphonyl-2,3:5,6-di-0-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-a-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-a-L-mannofuranose (41) into 1,4-dideoxy-1,4-imino-L- talitol hydrochloride (17). 2,3:5,6-Di-0-isopropylidene-ß-D-allofuranose (45) was converted via its oxime (46) into 4-0-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).

Original languageEnglish
Pages (from-to)699-706
Number of pages8
JournalJournal of the Chemical Society, Perkin Transactions 1
Issue number3
Publication statusPublished - 1990

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