Design and synthesis of pyrrolidine-containing sphingomimetics
- 1 January 2011
- journal article
- Published by Royal Society of Chemistry (RSC) in Organic & Biomolecular Chemistry
- Vol. 9 (12) , 4580-4586
Abstract
Based on the structures of natural sphingolipids, we designed heterocyclic sphingoid base mimetics in which the conformational restriction is introduced by incorporation of a pyrrolidine moiety between the 2-amino group and the C-4 carbon atom of the sphingoid base. Our synthesis features a regioselective nucleophilic ring opening of a cyclic sulfate with cyanide and subsequent manipulation of the cyanide group. During the course of synthesis, Staudinger-type reductive cyclization of 1,3-azido carboxylic acid and 1,4-azido alcohol offers a direct route to the five-membered pyrrolidone and pyrrolidine products. The preliminary biological evaluation indicates that the designed pyrrolidine analog is biologically active and its cytotoxic effect is associated with the induction of apoptosis.Keywords
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