Synthesis and SAR of vinca alkaloid analogues

Versatile intermediates 12′-iodovinblastine, 12′-iodovincristine and 11′-iodovinorelbine were utilized as substrates for transition metal based chemistry which led to the preparation of novel analogues of the vinca alkaloids. The synthesis of key iodo intermediates, their transformation into final products, and the SAR based upon HeLa and MCF-7 cell toxicity assays is presented. Selected analogues 27 and 36 show promising anticancer activity in the P388 murine leukemia model.

Graphical abstractThe development of selective iodination conditions for the dimeric vinca alkaloids vinblastine, vincristine, and semisynthetic derivative vinorelbine led to the preparation of new analogues of these important antitumor agents.Figure optionsDownload full-size imageDownload as PowerPoint slide