Syntheses of (−)-8-epi-Swainsonine and (−)-1,8-Di-epi-swainsonine, Stereoisomers of Physiologically Interesting Indolizidine Alkaloid, Swainsonine

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Inhibition of lysosomal alpha-mannosidase by swainsonine, an indolizidine alkaloid isolated from Swainsona canescens.

An indolizidine alkaloid (swainsonine) was isolated from the plant Swainsona canescens. Swainsonine is a specific and potent inhibitor of alpha-mannosidase (EC 3.2.1.24) and when administered to animals produces a phenocopy of the genetically based lysosomal storage disease, mannosidosis. Evidence is presented to suggest that swainsonine is a reversible active site-directed inhibitor of lysosom...

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Application of furyl-stabilized sulfur ylides to a concise synthesis of 8a-epi-swainsonine.

The total synthesis of 8a-epi-swainsonine has been achieved in 20% overall yield from R-glyceraldehyde dimethylacetonide 3 through epoxidation with the achiral furyl-substituted sulfonium ylide 2d as one of the key steps.

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Asymmetric synthesis of (-)-swainsonine

This paper describes a new synthesis of (-)-swainsonine via the ring-closing metathesis reaction of a substituted 3-allyl-4-vinyl-2-oxazolindinone and subsequent diastereoselective syn-dihydroxylation of the resulting pyrrolo[1,2-c]oxazol-3-one.

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Asymmetric total synthesis of (+)-swainsonine.

A concise asymmetric synthesis of (+)-swainsonine (ent-1) is described starting from 2, which was readily prepared from commercially available l-glutamic acid. The method features installation of the indolizidine ring via an intramolecular cyclisation of α-sulfinyl carbanion as a key step. (+)-Swainsonine was obtained in 11.8% overall yield in 10 steps.

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Structure-activity relationship of swainsonine. Inhibition of human alpha-mannosidases by swainsonine analogues.

The inhibitory properties of a series of synthetic epimers and analogues of swainsonine towards the multiple forms of human alpha-mannosidases were studied in vitro and in cells in culture. Of the five epimers tested, only the 8a-epimer and 8,8a-diepimer of swainsonine were specific and competitive inhibitors (Ki values of 7.5 x 10(-5) and 2 x 10(-6) M respectively) of lysosomal alpha-mannosida...

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ژورنال

عنوان ژورنال: Bulletin of the Chemical Society of Japan

سال: 1986

ISSN: 0009-2673,1348-0634

DOI: 10.1246/bcsj.59.3885