Synthesis of Albonoursin

Abstract

Treatment of the ester of 2-(2-chloroacetamido)-2-alkenoic acid with ammonia led to the formation of 3-alkylidene-2,5-piperazinedione. By using this method, total synthesis of albonoursin was accomplished. 2-(2-Chloroacetamido)-4-methyl-2-pentenoic acid, derived from the condensation of 4-methyl-2-oxopentanoic acid with chloroacetonitrile or the pyrolysis of 2,2-bis(2-chloroacetamido)-4-methylpentanoic acid, was converted to the ethyl ester, which was treated with ammonia to give 3-isobutylidene-2,5-piperazinedione. The piperazinedione was also synthesized by the esterification of 2-(2-aminoacetamido)-4-methylpentenoic acid, followed by a cyclization of the ester. Condensation of the piperazinedione with benzaldehyde yielded 3-benzylidene-6-isobutylidene-2,5-piperazinedione, and its physical constants are virtually identical with those recorded for the natural albonoursin.