Ms. Kuo et al., DISCOVERY, ISOLATION, STRUCTURE ELUCIDATION, AND BIOSYNTHESIS OF U-106305, A CHOLESTERYL ESTER TRANSFER PROTEIN INHIBITOR FROM UC-11136, Journal of the American Chemical Society, 117(43), 1995, pp. 10629-10634
During our screening of fermentation broths, culture UC 11136 was iden
tified as producing potent inhibitor(s) of the in vitro cholesteryl es
ter transfer protein (CETP) reaction. Subsequent chemical isolation wo
rk identified two inhibitors of CETP produced by this culture. One of
these inhibitors, U-106305, represented a novel CETP inhibitor as well
as a structural class of compounds not previously reported from micro
bial fermentations. The structure of U-106305 was elucidated as 3:16,1
7-hexamethylene-(E,E)-2,14-octadecadienamide by extensive NMR studies,
Biogenetically, the backbone of U-106305 was found to derive from nin
e acetates linked in a head-to-tail fashion, while the cyclopropyl met
hylene carbons were derived from the methyl group of L-methionine. A b
iosynthetic pathway is proposed based on these findings.