First total synthesis of the whole series of the antiostatins A and B

摘要

The first synthesis of the whole antiostatin family is described by using an iron-mediated carbazole synthesis, regioselective nitration at C-4 and establishing 5-isobutyl-1-nitrobiuret as a reagent for introduction of the antiostatin B side chain at C-4.rnCurrently, carbazoles are of high interest due to their pharmacological potential. In 1990, Seto et al. at the University of Tokyo isolated the antiostatins A_1 to A_4 and B_2 to B_5 from Streptomyces cyaneus 2007-SV_1 (Fig. 1). They exhibit a strong inhibitory activity against free radical induced lipid peroxidation. The antiostatins are structurally unique because of their nitrogen substituent at C-4, which is part of an isobutylbiuret side chain for the antiostatins B. So far, no synthesis has been reported for any member of this family of carbazoles, despite synthetic efforts by several groups in the field. In the present paper, we describe the first total synthesis of all antiostatins.