Synthesis of Antimitotic Analogs of the Microtubule Stabilizing Sponge Alkaloid Ceratamine A

Abstract

Antimitotic analogs of the microtubule stabilizing sponge alkaloid ceratamine A (1) have been synthesized starting from tribromoimidazole. A key step in the synthesis is the formation of the azepine ring via an intramolecular Buchwald coupling between a vinyl bromide and a N-methyl amide. This represents the first synthesis of a fully unsaturated imidazo[4,5,d]azepine. NMR data obtained for the synthetic ceratamine analogs has provided support for the structure assigned to the natural product.