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

The title compounds were synthesized by the efficient route previously explored for the synthesis of enantiomeric pairs of thiolactomycin and its 3-demethyl derivative. These studies were carried out to prove the flexibility of the previously explored synthetic route to natural thiolactomycin (TLM)...

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Published inChemical & pharmaceutical bulletin Vol. 57; no. 9; pp. 920 - 936
Main Authors Ohata, Kohei, Terashima, Shiro
Format Journal Article
LanguageEnglish
Published TOKYO The Pharmaceutical Society of Japan 01.09.2009
Pharmaceutical Soc Japan
Japan Science and Technology Agency
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Summary:The title compounds were synthesized by the efficient route previously explored for the synthesis of enantiomeric pairs of thiolactomycin and its 3-demethyl derivative. These studies were carried out to prove the flexibility of the previously explored synthetic route to natural thiolactomycin (TLM) 1 and to examine the structure–activity relationship on the 5-position of 1. While all of the synthesized congeners lacked in vitro antibacterial activity, these studies led us to find 5-(alk-2-enyl)-TLM (ent-4d) which exhibits mammalian type I fatty acid synthase (FAS) inhibitory activity equal to that of C75, a potent inhibitor reported previously. It was also found that 5-[(E)-cycloalk-2-enylidenemethyl]-TLM (ent-5c) exhibited slightly less potent mammalian type I FAS inhibitory activity than C75.
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ISSN:0009-2363
1347-5223
DOI:10.1248/cpb.57.920