Synthesis Of Podophyllotoxin Derivatives And Research Of Anti-tumor Activity

Podophyllotoxin is a anti-tumor natural lignan compounds isolated from Podophyllum peltatum L.,P.emodi W.,or P.Pleianthum H. It inhibit the formation of tumor cell growth by blocking mitotic cell microtubules, and colchicine have similar anti-tumor mechanism. Although it has significant anti-tumor activity, but the toxic side effects, especially gastrointestinal toxicity is large, not suitable for direct clinical use, therefore, the structural transformation of podophyllotoxin were synthesized and screened more toxic than small and strong anti-tumor activity of derivatives to become a hot topic in domestic and foreign scholars. In this paper, the existing domestic and international research results and the structural characteristics of podophyllotoxin in the structure-activity relationship of podophyllotoxin on the basis of the structural modification of podophyllotoxin and get the new structure, a series of compounds that cytotoxic activity in vitro is better.This thesis is divided into three parts, the first chapter of the international study of podophyllotoxin and its derivatives progress, mainly podophyllotoxin and its derivatives from the antitumor mechanism, and in recent years, rese-archers modified the structure of podophyllotoxin discussion of two aspects of the system and summarizes the structure-activity relationship of the compound, as the basis for our research work. The second chapter is a structure-activity relationship of podophyllotoxin on the basis of the argument, presented the design of podophyllotoxin derivatives and synthetic methods, the use of mild reaction conditions of the Beckmann Rearrangement, containing N atoms are seven-C ring compounds to obtain a series of podophyllotoxin in the seven-ring analogs C, while for the future nucleus of podophyllotoxin partial amino acid structure of compounds to build the foundation.