Synthesis And Activity Study On Analogues Of Combretastatin A-4

Diphenylethene compound—Combretastatin A-4 was approved to be a kind of polysubstitution natural product which has important biological activity and wide application prospect. Due to the limited natural products resource and structure-activity relationship, modification for this kind of natural product has important social significance and evidently economic benefits. Because of the C=C double bond, diphenylethene compounds have cis-trans isomerism. It was reported that only the cis isomer can destroy effectively the tumor blood vessels. But the trans isomer would have side effects on normal cells. Moreover, the cis isomer of CA-4 derivatives would transform to trans structure under ultraviolet light. Which makes it must be kept under low temperature and without light. So, requirements on the separation and purification become higher. Huge raw materials consumption, high processing cost and low yield bring great difficulty in conservation and practical application. Therefore, modification of CA-4 derivatives to get more biologically active products is a very intresting research subject.This dissertation was mainly consisting of the following two parts:1. A series of ethoxy diphenylethane derivatives were designed and synthesized base on the structure-activity relationship of CA-4 analogues. All compounds were characterized and evaluated for their antitumor activities.2. An optimized synthesis process of CA-4 derivatives was made. Which avoid the high cost, high pollution, complex process, low yield and not easy to industrialization.