New 1Z,5Z-diene compounds: Stereoselective synthesis of tetraenoic macrodiolides

Macrocyclic compounds, including macrolactones and macrodiolides, play a significant role in the development of supramolecular chemistry, materials science, the perfume industry and pharmaceuticals. In previous studies conducted by our group over several years, previously undescribed macrocyclic compounds containing pharmacophoric 1Z,5Z-diene fragments in their structure were synthesized for the first time, which showed high potential during research of cytotoxicity, apoptosis-inducing activity, effects on the cell cycle and mitochondria in tumors cell lines (Jurkat, K562, U937).
As part of continuing research on the development of methods for the synthesis of new unsaturated macrodiolides and the study of their antitumor properties, in this work, for the first time, stereoselective synthesis of macrocyclic compounds based on 1,14-tetradeca-5Z,9Z-dienoic acid and α,ω-alka-nZ, ( n+4)Z-dienediols (1,12-dodeca-4Z,8Z-dienediol, 1,14-tetradeca-5Z,9Z-dienediol, 1,16-octadeca-6Z,10Z-dienediol) in good yields. The method for the synthesis of new macrodiolides is based on the previously well-proven reaction of direct intermolecular cyclocondensation of dienedioic acid with diene diols in the presence of 5 mol. % hafnium(IV) triflate. As a result of the experiments, it was shown that the reaction between 1,14-tetradeca-5Z,9Z-dienedioic acid and 1,16-octadeca-6Z,10Z-dienediol in toluene proceeds within 18 hours with the highest yield of 76% with the formation of previously undescribed tetraenoic macrodiolides containing two 1Z,5Z-diene fragments in their structure.