Glycosidase inhibitors: Synthesis of enantiomerically pure aza-sugars from Schiff base amino esters via tandem reduction-alkenylation and osmylation

Robin Polt, Dalibor Sames, Jason Chruma

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Nitrogen-in-the-ring 'aza-sugars' have been synthesized in enantiomerically pure form from the amino acid L-alanine in excellent overall yield. The O'Donnell's Schiff base of L-alanine methyl ester 9a was converted to aza-sugar L-fuco-1-deoxy-nojirimycin, 18, and to the epimer L-gulo-1- deoxy-nojirimycin, 20, in eight steps. The overall yields were 20 and 29%, respectively. The methodology for the efficient generation of silyl- and benzyl-protected (E)-3-lithio-2-propen-1-ols, and the use of these alkenyllithiums with iBu5Al2H as nucleophiles in the threo-selective tandem reduction-alkenylation of the Schiff base esters is described. Osmium- catalyzed cis-oxygenation of the resulting olefin products was selective for the galacto (fuco) amino polyols in all cases for the acyclic olefins, and was gulo-selective for the cyclic D-4,5-dihydropyridine pivalate, 17c. TEMPO- NaOCl was selective for oxidation of the primary position of the acyclic Schiff bases, and allowed for minimal protection/deprotection of the intermediates. The resulting N-benzhydryl heterocycles were easily deprotected with H2-Pd at atmospheric pressure.

Original languageEnglish (US)
Pages (from-to)6147-6158
Number of pages12
JournalJournal of Organic Chemistry
Volume64
Issue number17
DOIs
StatePublished - Aug 20 1999

ASJC Scopus subject areas

  • Organic Chemistry

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