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 in studies on cytotoxicity, apoptosis-inducing activity, effects on the cell cycle, and mitochondria in tumor cell lines (Jurkat, K562, U937). As part of the continuing research on the development of methods for synthesizing new unsaturated macrodiolides and studying their antitumor properties, this work presents, for the first time, the 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 proceeded within 18 h with the highest yield of 76%, with the formation of previously undescribed tetraenoic macrodiolides containing two 1Z,5Z-diene fragments in their structure.