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Design and synthesis of pyrrolidine-containing sphingomimetics†
Seokwoo Lee,Sukjin Lee,Hyen Joo Park,Sang Kook Lee,Sanghee Kim
Organic & Biomolecular Chemistry Pub Date : 05/03/2011 00:00:00 , DOI:10.1039/C1OB05324H
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.

Graphical abstract: Design and synthesis of pyrrolidine-containing sphingomimetics
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