Synthesis of combretastatin A-4 and its water-soluble analogues

Objective: To synthesize the anticancer agent combretastatin A-4 and its water-soluble analogues. Methods: 3,4,5-Trimethoxyphenylacetic acid and isovanilline were used as starting materials to prepare combretastatin A-4 and its water-soluble analogues via condensation, modification with mPEG side chain, and de-carboxylation reactions. Results: The structures of target compounds were confirmed by ¹H NMR, ¹³C NMR, MS and melting point; the overall yields were about 40%. Conclusion: The synthetic routes developed herein require simple reaction conditions and few steps, and yield high stereoselectivity of cis conformation, which are suitable for large-scale manufacturing.