Synthetic & computational studies towards conidiogenone B

Abstract

Total synthesis of tetracyclic diterpene natural product, conidiogenone B, has been attempted, which is known for its anticancer and antibacterial activity. Key-steps include Eschenmoser-Tanabe fragmentation, Wang allenation, and intramolecular [3+2] TMM diyl-olefin cycloaddition reaction. To our surprise, a bridged isomer, rather than a linear isomer, has been obtained from the cycloaddition, which led us to revise the synthetic approach and to conduct model studies. The synthetic and computational model studies revealed that an extra methyl group on TMM diyl and/or an electron-withdrawing group on olefin, can dictate the regioselectivity of the cycloaddition.