First total synthesis and antileishmanial activity of (Z)-16-methyl-11-heptadecenoic acid, a new marine fatty acid from the sponge Dragmaxia undata.
The first total synthesis for the (Z)-16-methyl-11-heptadecenoic acid, a novel fatty acid from the sponge Dragmaxia undata, was accomplished in seven steps and in a 44% 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 10-bromo-1-decanol followed by a second acetylide coupling to the short-chain 1-bromo-4-methylpentane, which resulted in higher yields. Complete spectral data is also presented for the first time for this recently discovered fatty acid and the cis double bond stereochemistry of the natural acid was established. The title compound displayed antiprotozoal activity against Leishmania donovani (IC(50) = 165.5 ± 23.4 μM) and inhibited the leishmania DNA topoisomerase IB enzyme (LdTopIB) with an IC(50) = 62.3 ± 0.7 μM.
Department of Chemistry, University of Puerto Rico, San Juan, 00931-3346, USA. nmcarballeira@uprrp.edu
Néstor M
NM
Carballeira
Nashbly
N
Montano
Gabriel A
GA
Cintrón
Carmary
C
Márquez
Celia Fernández
CF
Rubio
Christopher Fernández
CF
Prada
Rafael
R
Balaña-Fouce
D000114:Acetylene / Q000737:chemistry; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D005227:Fatty Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D005229:Fatty Acids, Monounsaturated / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D007202:Indicators and Reagents / Q000737:chemistry; D007893:Leishmania donovani / Q000187:drug effects* / Q000201:enzymology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D011161:Porifera / Q000737:chemistry*; D013237:Stereoisomerism; D059003:Topoisomerase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity
C420903:16-methyl-8-heptadecenoic acid; D000981:Antiprotozoal Agents; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D007202:Indicators and Reagents; D059003:Topoisomerase Inhibitors; D004264:DNA Topoisomerases, Type I; D000114:Acetylene