Synthesis and Study of the Structure and Cytotoxicity of Five-Membered Cyclic Structural Analogs of Combretastatin A4

An original method was proposed for the synthesis of 5-(cyclopent-1-en-1-yl)-1,2,3-trimethoxybenzene with an overall yield of about 70%. The method involves metallation of 5-bromo-1,2,3-trimethoxybenzene, reaction of the lithium derivative with cyclopentanone, and dehydration using p-toluenesulfonic acid. The corresponding diarylcyclopentene analogs of combretastatins were synthesized via a cross-coupling reaction of this cyclopentene with aryl iodides. The Pd(OAc)2/Ag2CO3 catalytic system was found to be effective in this cross-coupling reaction. A significant level of cytotoxicity against HuTu-80, U118, HepG2, and B16 tumor cells was revealed for the cyclopentene analogs of combretastatins (MTT assay).