TOTAL SYNTHESIS OF ACANTHACEREBROSIDE-A AND ASTROCEREBROSIDE-A VIA A CHIRAL EPOXIDE INTERMEDIATE DERIVED FROM L-QUEBRACHITOL

The chiral and stereoselective total synthesis of novel cerebrosides, acanthacerebroside A (1) and astrocerebroside A (2), isolated from sta rfish, is described. The phytosphingosine moieties in 1 and 2 were pre pared by the coupling reaction of dialkylmagnesium reagents with the c ommon epoxide intermediate, 2-deoxy-3-O-(4-methoxybenzyl)-D-4,5-anhydr oribitol (5). The epoxide (5) was synthesized from naturally occurring cyclitol, L-quebrachitol via the conduramine derivative, which was pr epared regio-and stereoselectively by the Pd-catalyzed azidation of th e allyl carbonate derivative. Condensation of phytosphingosines with 2 -acetoxy fatty acid residue, followed by glycosidation, furnished the total synthesis. This work established an effective synthetic pathway to a wide variety of cerebrosides containing various phytosphingosines and 2-hydroxy fatty acid residue; the first total synthesis of astroc erebroside A (2) fully confirmed the proposed structure.