構造の特異な生理活性物質の合成研究−環状エンジイン化合物の合成研究−

Abstract

Cyclic enediyne antibiotics such as calicheamicin and dynemicin A exhibit extraordinary potent antitumor activities through DNA cleavage by phenylene diradical, which is generated by Bergman reaction of the 10-membered enediyne moiety. To mimic this action mechanism of dynemicin A, we designed the two simplified compounds model A and model B having epoxide and 10-membered enediyne ring, and synthesized these molecules. The model A did not undergo the Bergman reaction under acidic conditions, while the model B exhibited DNA cleavage and in vitro cytotoxicity. Both enantiomers of the model B were also synthesized. In the synthesis of a model compound of calicheamicin, we examined cyclization conditions of an enediyne aldehyde to find out NHK reaction was the most reliable. During these studies, several new reactions were developed, such as reaction of N-acyliminium cation with silyl- and tin-acetylene, palladium catalyzed coupling reaction of allyl derivatives and tinacetylene, remote asymmetric induction in acetylide addition to quinoline nucleus, and one pot synthesis of haloacetylene from silylacetylene.