Synthesis and Biological Activity of Enantiomeric Pairs of 5-(Alk-2-enyl)thiolactomycin and 5-[(E)-Cycloalk-2- enylidenemethyl]thiolactomycin Congeners~(1,2))

摘要

The title compounds were synthesized by the efficient route previously explored for the synthesis of enan-tiomeric pairs of thiolactomycin and its 3-demethyl derivative. These studies were carried out to prove the flexi-bility of the previously explored synthetic route to natural thiolactomycin (TLM) 1 and to examine the struc-ture—activity relationship on the 5-position of 1. While all of the synthesized congeners lacked in vitro antibacter-ial activity, these studies led us to find 5-(alk-2-enyl)-TLM (ent-4d) which exhibits mammalian type I fatty acidsynthase (FAS) inhibitory activity equal to that of C75, a potent inhibitor reported previously. It was also foundthat 5-[(E)-cycloalk-2-enylidenemethyll-TLM (ent-5c) exhibited slightly less potent mammalian type I FAS in-hibitory activity than C75.