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.