Synthetic Study Of Podophyllotoxin Analogs

Podophyllotoxin, as an excellent anti-tumour plant compound, play an important role in medicine research. Synthesis and activation study of its analogs become a hotspot of anticancer study. Therefore, several podophyllotoxin analogs were designed and synthesized. Sugar-modification is an important method to reduce medicine toxicity. So, a novel sugar-modified method was presented and the necessary palladium ligand was successfully synthesized in the present paper.A series of novel three-ring podophyllotoxin analogs were designed and nine title compounds were obtained. In order to accomplish etherification of those podophyllotoxin analogs and sugars, a palladium ligand was synthesized in present paper.Several substituted bromobenzene were reacted with magnesium to give the Grignard reagents, which were treated with aldehydes to give the diphenylmethanols in 23%-77% yield. Those abtained phenylmethanols were chlorinated with thionyl chloride, and then reacted with pyrrolidine to give the title compounds in 20%-72%. Some diphenylmethanols were easily oxided into the corresponding acetones in air, which can reduce to the corresponding alcohol with sodium borohydride and then completed the following reactions.Started from 2-naphthylamine, 1,1'-binaphthyl-2,2'-diamine was obtained via oxidation, couple reaction and rearrangement. Then 2'-bromine-2-N,N-dimethyl-1,1'- binaphthylamine was synthesized via diazotization, bromination and methyllation in 49.7% yield. 2'-bromine-2-N,N-dimethyl-1,1'-binaphthylamine was treated with n-butyllithium, and then reacted with di-t-butylchlorophosphine to give the title compound in 66.9% yield. The overall yield of the four-stepped reaction was 33.3%.