Stereostrueture and Synthesis of Aplyronine A, an Antitumor Substance of Marine Origin

Abstract

Aplyronine A (1), isolated as a very minute constituent of the sea hare Aplysia kurodai, is a new potent antitumor macrolide that interacts with actin, the protein in cytoskeleton. The absolute stereostructure of aplyronine A (1) was determined by the spectroscopic analysis and the enantioselective synthesis of the fragments derived from 1. The enantioselective synthesis of aplyronine A (1) was achieved by a convergent approach. Three segments 28, 29, and 30 were prepared using the Evans aldol reaction and the Sharpless epoxidation as key steps. The segment 28 was combined with two segments 31 and 32 successively to afford segment 33, while the Julia coupling reaction between segments 29 and 30 gave segment 34. Julia olefination between segments 33 and 34 and the subsequent four-carbon homologation reaction led to seco acid 35, which was converted into aplyronine A (1) by Yamaguchi lactonization followed by the introduction of two amino acids.