Total Syntheses of Isodomoic Acids G and H

摘要

Isodomoic acids G (1) and H (2) were isolated in 1997 by Arakawa from red alga Chondria armata. They belong to the family of kainoid amino acids, which includes kainic acid, domoic acid, and isodomoic acids, a series of structurally related natural products bearing a 3-carboxymethylproline moiety and a side chain on C(4). These compounds differ in the position and configuration of the double bond at C(4). Kainoid amino acids have long been recognized as neuroexcitatory agents, and their high potency makes them extremely valuable as research tools in neuroscience as well as medicinal chemistry. In fact, in 2000 the shortage of kainic acid threatened to hamper research projects in neurodegenerative diseases, and a call for new supplies for isolation or synthesis was issued. Even now, the price of kainic acid remains extremely high, and other kainoid derivatives are obtained in only minute quantities from natural sources. In response, many syntheses of kainic acid have been reported, whereas those of other kainoids have only been sparsely documented. Notably, however, Montgomery recently disclosed an elegant synthesis of isodomoic acid G that also unambiguously established its absolute configuration.