Total synthesis of acanthacerebroside A and astrocerebroside A via a chiral epoxide intermediate derived from L-quebrachitol

Article abstract of DOI:10.1246/bcsj.71.259

The chiral and stereoselective total synthesis of novel cerebrosides, acanthacerebroside A (1) and astrocerebroside A (2), isolated from starfish, is described. The phytosphingosine moieties in 1 and 2 were prepared by the coupling reaction of dialkylmagnesium reagents with the common epoxide intermediate, 2-(t-butoxycarbonyl)amino-1-O-(t-butyldiphenylsilyl)-2-deoxy- 3-O-(4-methoxybenzyl)-D-4,5-anhydroribitol (5). The epoxide (5) was synthesized from naturally occurring cyclitol, L-quebrachitol via the conduramine derivative, which was prepared regio- and stereoselectively by the Pd-catalyzed azidation of the 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 astrocerebroside A (2) fully confirmed the proposed structure.