Second-Generation, Biomimetic Total Synthesis of Chaetominine

Abstract

A straightforward total synthesis of the potent anticancer agent (-)-chaetominine is reported. Central to this synthesis was a biomimetic oxidative cyclization of a tryptophanyl-alanine dipeptide, which provided a fully elaborated 1,2,3,4-tetrahydropyrido[2,3-b]indole. Reduction of this intermediate followed by spontaneous cyclization and installation of the side chain provided synthetic chaetominine in a nine-step sequence in 14% overall yield starting from commercially available, inexpensive starting materials.

alkaloids - total synthesis - oxidative cyclization - anticancer agents - peptides

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Electrostatic repulsion between the phthalimide protecting group and the incoming electrophile might also account for the high stereoselectivity observed

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