Total Synthesis of Acanthacerebroside A and Astrocerebroside A via a Chiral Epoxide Intermediate Derived from L-Quebrachitol

• Published in: Bulletin of the Chemical Society of Japan 1998-01, Vol.71 (1), p.259-272
• Main Authors: Chida, Noritaka, Sakata, Noboru, Murai, Katsuyuki, Tobe, Takahiko, Nagase, Toshihiko, Ogawa, Seiichiro
• Format: Article
• Language: English
• ISSN: 0009-2673; 1348-0634
• 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.