Preliminary Research On The Improvement Of The Total Synthesis Of Antineoplastic Agent Combretastatin A-4

Preliminary research on the improvement of the total synthesis of an antineoplastic drug Combretastatin A-4 (CA4) was described in the dissertation. The stilbene Combretastatins are a group of antimitotic agents isolated from the bark of the south Africa tree,Combretum caffrum. As a new potent cytotoxic agent that is able to elicit irreversible vascular shutdown within solid tumors, it can inhibit the growth of many tumors. So, a valuable clinical application is prospected. However, although many total synthesis routes have been devised so far, as far as industrial production is concerned, all of these routes have limitations to some extent. To achieve this aim, the synthesis route which was based on Wittig reaction was improved. Therefore, 3-hydroxy-4-methoxy benzyltriphenylphosphonium bromide was prepared starting from 3-hydroxy-4-methoxybenzaldehyde in two steps. The phosphonium and 3,4,5-trimethoxybenzaldehyde were dissolved in suitable solvents and heated at reflux under nitrogen protection in the presence of reagent 1, reagent 2, reagent 3, reagent 4 respectively, yielding Combretastatin A-4. Because of the similar polarity of cis- and trans- Combretastatin A-4, it is difficult for separation. Research aimed on convertion of trans- Combretastatin A-4 into cis- Combretastatin A-4 is under way in our labortary.