Piperidine analogues of D-galactose as potent inhibitors of a-galactosidase: Synthesis by stannane-mediated hydroxymethylation of 5-azido-l,4-lactones. Structural relationships between D-galactosidase and L-rhamnosidase inhibitors

John P. Shilvock, Robert J. Nash, Alison A. Watson, Ana L. Winters, Terry D. Butters, Raymond A. Dwck, David Winkler, George W J Fleet

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24 Citations (Scopus)

Abstract

The syntheses of the polyhydroxylated piperidines deoxygalactonojirimycin 2, homogalactonojirimycins 7 and 9, and other 2,6-iminoheptitol derivatives, including an analogue of L-altropyranose, are reported. 5-Azidoaldono1,4-lactones undergo chain extension to afford azido lactols by the addition of a hydroxymethyllithium species 18, generated by transmetallation of a protected stannylmethanol derivative 17. Hydrogénation results in azide reduction with subsequent intramolecular reductive amination to give piperidine ring systems. The deprotected iminogalactopyranose analogues are potent and selective a-galactosidase inhibitors. Observations on the structural features determining selectivity of inhibition of a-galactosidases over naringinase (L-rhamnosidase) are also reported. © The Royal Society of Chemistry 1999.

Original languageEnglish
Pages (from-to)2747-2754
Number of pages8
JournalJournal of the Chemical Society, Perkin Transactions 1
Issue number19
Publication statusPublished - 1999
Externally publishedYes

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