Stereoselective syntheses of 1,4-dideoxy-1,4-imino-octitols and novel tetrahydroxyindolizidines
A new route for the preparation of four new indolizidines, (1R,2S,6S,7S,8aS)- and (1R,2S,6R,7R,8aS)-1,2,6,7-tetrahydroxyindolizidine (30 and 32) and (1S,2R,7S,8S,8a-R)- and (1S,2R,7R,8R,8a-R)1,2,7,8-tetrahydroxyindolizidine (44 and 46), is reported. The synthesis is based on Knoevenagel homologation of the readily available enantiomerically pure pyrrolidin-carbaldehydes 13 and 37 followed by asymmetric dihydroxylation of the subsequent alkenyl pyrrolidines and cyclization of the corresponding imino-octitols. The new indolizidines and their precursors (imino-octitols 20, 25, 26) and indolizidinones 28a and 28b have been tested for inhibitory activities toward 26 glycosidases. The enzymatic inhibition of trans-7-hydroxy-D-(-)-swainsonine (44) toward alpha-mannosidases is similar to that described for trans-7-hydroxy-L-(+)-swainsonine (11b) toward naringinase (alpha-L-rhamnosidase from Penicillium decumbens).
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Keywords: Aza-c-disaccharides ; alpha-mannosidase inhibitor ; glycosidase ; inhibitors ; imino disaccharides ; asymmetric dihydroxylation ; 4-octulose ; derivatives ; biological evaluation ; convergent synthesis ; swainsona-canescens ; sugar mimics
Univ Sevilla, Fac Quim, Dept Quim Organ, E-41071 Seville, Spain. Swiss Fed Inst Technol, Inst Mol & Biol Chem, BCH, CH-1015 Lausanne, Switzerland. Inst Grassland & Environm Res, Aberystwyth 5423 3EB, Dyfed, Wales.
Record created on 2005-11-09, modified on 2016-08-08