First total synthesis and antiprotozoal activity of (Z)-17-methyl-13-octadecenoic acid, a new marine fatty acid from the sponge Polymastia penicillus.
The first total synthesis for the (Z)-17-methyl-13-octadecenoic acid was accomplished in seven steps and in a 45% overall yield. The use of (trimethylsilyl)acetylene was key in the synthesis. Based on a previous developed strategy in our laboratory the best synthetic route towards the title compound was first acetylide coupling of (trimethylsilyl)acetylene to the long-chain protected 12-bromo-1-dodecanol followed by a second acetylide coupling to the short-chain 3-methyl-1-bromobutane, which resulted in higher yields. Complete spectral data is also presented for the first time for this recently discovered fatty acid. The title compound displayed antiprotozoal activity against Leishmania donovani (EC(50) = 19.8 microg/ml) and inhibited the leishmania DNA topoisomerase IB at concentrations of 50 microM.
Carballeira
Néstor M
NM
Department of Chemistry, University of Puerto Rico, San Juan, Puerto Rico 00931-3346. nmcarballeira@uprrp.edu
Montano
Nashbly
N
Balaña-Fouce
Rafael
R
Prada
Christopher Fernández
CF
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D007893:Leishmania donovani / Q000187:drug effects* / Q000201:enzymology; D009829:Oleic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011161:Porifera / Q000737:chemistry*
D000981:Antiprotozoal Agents; D009829:Oleic Acids; C037352:13-octadecenoic acid; D004264:DNA Topoisomerases, Type I