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The first Z-stereoselective method for the synthesis of the natural marine alkynol lembehyne C, containing a 1Z,5Z,9Z-triene moiety, in 41% yield was developed using the new Ti-catalyzed cross-coupling of oxygenated and aliphatic 1,2-dienes as the key step. It was found for the first time that lembehyne C exhibits moderate cytotoxicity against Jurkat, K562, U937, and HL60 cancer cells and also efficiently induces apoptosis in Jurkat cells, with the cell death mechanism being activated by the mitochondrial pathway. The lembehyne C inhibition of the cell cycle follows the mitotic catastrophe mechanism.

An original method for the total synthesis of natural grenadamide and its precursor lyngbyoic acid with high stereoselectivity and yields was developed using the catalytic cycloalumination reaction of 1,2-dienes with Et3Al in the presence of 5 mol.% of Cp2ZrCl2 (Dzhemilev reaction) as a key step.

The communication reports a new stereoselective method for the synthesis of a natural acetylenic alcohol, lembehyne B. The key stage of the process uses new cross-cyclomagnesiation reaction of aliphatic and oxygenated 1,2-dienes with Grignard reagents in the presence of a catalytic amount of Cp2TiCl2. A study of the cytotoxic properties of lembehyne B on tumor cell lines using flow cytometry demonstrated that this is a selective inducer of early apoptosis of the Jurkat, HL-60 and K562 cell cultures and hypodiploid (sub-G1) sub-population inducer in cell cycle studies for all cell lines used.

An original method has been developed for the synthesis of 1,3-dyine derivatives of natural lembehyne B in high yields (50–67%) and with high selectivity (>98%). The key stage of the synthesis is new Ti-catalyzed cross-cyclomagnesiation of oxygenated and aliphatic 1,2-dienes induced by Grignard reagents. For studying the effect of the structure on the antitumor and neuritogenic activities, a series of lembehyne B analogues with different distances between the terminal hydroxy group and the 1,3-diyne moiety was prepared and tested for neuritogenic activity on mouse neuroblastoma Neuro 2A cells and for cytotoxicity, induction of apoptosis, and effects on the cell cycle using Jurkat, U937, K562, HeLa, and Hek293 tumor cell lines.

Natural (5Z,9Z)-dienoic acids and key precursors of biologically active trienoic acids were prepared in high yields and with high stereoselectivity using cross-cyclomagnesiation of terminal and oxygenated 1,2-dienes with EtMgBr in the presence of Mg metal and Cp2TiCl2 catalyst at the key step.

The total synthesis of lembehyne B was accomplished in five steps in 51% total yield. The cross-cyclomagnesiation of two allenic components, nonadeca-1,2-diene and pentadeca-13,14-dien-1-ol tetrahydropyranyl ether, with EtMgBr in the presence of Mg and Cp2TiCl2 catalyst (10 mol%) was used in the key step of the synthesis.