First total synthesis and antiprotozoal activity of (Z)-17-methyl-13-octadecenoic acid, a new marine fatty acid from the sponge Polymastia penicillus

Carballeira, Néstor M.; Montano, Nashbly; Balaña‐Fouce, Rafael; Fernández-Prada, Christopher

doi:10.1016/j.chemphyslip.2009.06.140

Cited by 15 publications

(11 citation statements)

References 13 publications

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“…In fact, we have shown that the acid ( Z )-14-methyl-9-pentadecenoic acid, also a monounsaturated iso methyl-branched fatty acid, inhibits the human DNA topoisomerase I but at the higher concentrations of 500 µM (Carballeira et al, 2007). Therefore, the present findings corroborate our previous results that monounsaturated iso methyl-branched fatty acids are more effective towards the LdTopIB than the human DNA topoisomerase I (Carballeira et al, 2009). …”

Section: Resultssupporting

confidence: 92%

“…strain KM86-9B displayed topoisomerase I inhibitory activity (Lee et al, 1998). In fact, we have also shown that the acid ( Z )-14-methyl-9-pentadecenoic acid inhibits the human placenta DNA topoisomerase I enzyme at concentrations of 500 µM (Carballeira et al, 2007), while the marine fatty acid ( Z )-17-methyl-13-octadecenoic acid inhibits the leishmania DNA topoisomerase IB enzyme at concentrations of 50 µM (Carballeira et al, 2009). The latter report indicated that these iso monounsaturated fatty acids do have antiprotozoal potential.…”

Section: Introductionmentioning

confidence: 95%

“…However, by applying our previous developed synthetic methodology for unsaturated iso methyl-branched fatty acids (Carballeira et al, 2009) to the synthesis of 1 enough material for such studies could be obtained. Therefore, in order to unequivocally conclude the total characterization of 1 , i.e., determine the cis or trans double bond stereochemistry, as well as to study its antileishmanial activity we are reporting herein the first total synthesis for the ( Z )-16-methyl-11-heptadecenoic acid ( 1 ).…”

Section: Introductionmentioning

confidence: 99%

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First total synthesis and antileishmanial activity of (Z)-16-methyl-11-heptadecenoic acid, a new marine fatty acid from the sponge Dragmaxia undata

Carballeira¹,

Montano²,

Cintrón³

et al. 2011

Chemistry and Physics of Lipids

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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 (IC50 = 165.5 ± 23.4 µM) and inhibited the leishmania DNA topoisomerase IB enzyme (LdTopIB) with an IC50 = 62.3 ± 0.7 µM.

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Section: Resultssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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First total synthesis and antileishmanial activity of (Z)-16-methyl-11-heptadecenoic acid, a new marine fatty acid from the sponge Dragmaxia undata

Carballeira¹,

Montano²,

Cintrón³

et al. 2011

Chemistry and Physics of Lipids

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“…Un autre isomère, le nouvel acide 17-méthyl-13(Z)-octadécènoïque a été récem-ment caractérisé chez P. penicillus (Denis et al, 2009). C'est l'acide iso-ramifié nonadécènoïque avec la double liaison la plus proche de l'extré-mité de la chaîne, en n-5, et il a été obtenu par synthèse organique en raison de son activité contre le protozoaire Leishmania (Carballeira et al, 2009). Cette observation est renforcée par le fait que ce dernier AG semble provenir d'un allongement dicarboné de la chaîne de l'acide bactérien 15-méthyl-11(Z)-hexadé-cènoïque isolé de plusieurs sources, mais surtout chez Myxococcus xanthus (Boon et al, 1977 ;Reyes et Carballeira, 1996).…”

Section: Ag Mono-insaturés Et Ramifiésunclassified

Acides gras inhabituels des organismes marins : une illustration de la biodiversité moléculaire marine

Barnathan

2010

OCL

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In addition to the common polyunsaturated fatty acids (FA) such as those of the n-3 and n-6 series with major interest in health and nutrition, marine organisms (invertebrates and algae) produce unique FA including branched, methoxylated, halogenated, acetylenic and non-methylene-interrupted structures. The biosynthetic pathways, and the structural and functional roles of these uncommon FA are often not yet known. This short overview wishes to be an outline on the particular FA classes possessing uncommon structures, especially those of increasing interest regarding their promising biological activities.

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“…We had previously shown that the iso methyl-branched monounsaturated fatty acid ( Z )-17-methyl-13-octadecenoic acid displays antileishmanial activity towards Leishmania donovani promastigotes with an EC 50 = 19.8 ± 7.0 µg/ml and, as a probable intramolecular target, inhibits the leishmania DNA topoisomerase IB enzyme at concentrations of 50 µM 9. Given these previous results we decided to test the cis cyclopropane fatty acid 1b against L. donovani promastigotes and establish how cyclopropane substitution compares to monunsaturation in determining the antileishmanial activity of these iso -C 18 fatty acids 10.…”

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The first total synthesis of the (±)-17-methyl-trans-4,5-methyleneoctadecanoic acid and related analogs with antileishmanial activity

Carballeira

Montano

Reguera

et al. 2010

Tetrahedron Letters

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The first total synthesis of the marine cyclopropane fatty acid (±)-17-methyltrans-4,5-methyleneoctadecanoic acid was accomplished in 8 steps and in 9.1% overall yield starting from 1-bromo-12-methyltridecane. The cis analog (±)-17-methyl-cis-4,5-methyleneoctadecanoic acid was also synthesized but in 7 steps and in 16.4% overall yield. With the two isomeric cyclopropane fatty acids at hand it was possible to unequivocally corroborate the trans relative configuration of the naturally occurring fatty acid by gas chromatographic co-elution of the corresponding methyl esters. The cis isomer was cytotoxic to Leishmania donovani promastigotes with an IC 50 of 300.2 ± 4.2 µM. KeywordsAntileishmanial activity; Cyclopropane fatty acids; Sponges; Synthesis Cyclopropane fatty acids (CFAs) are widespread in nature and they have been identified in many organisms ranging from bacteria to seed oils. 1 The earliest known example is lactobacillic acid (cis-11,12-methyleneoctadecanoic acid), but several structural variants have been isolated since. 1 One interesting compound is the 17-methyl-cis-9,10-methyleneoctadecanoic acid, from the protozoan Herpetomonas megaseliae, which incorporates both methyl and cyclopropyl branching in the chain. 2 While most of the known CFAs incorporate a cis cyclopropyl group in the acyl chain, just a few trans CFAs are known, such as the recently discovered 17-methyl-trans-4,5-methyleneoctadecanoic acid (1a) and the 18-methyl-trans-4,5-methylenenonadecanoic acid, which were identified in the phospholipids of the Caribbean sponge Pseudospongosorites suberitoides. 3 These marine fatty acids are quite interesting since they incorporate an unusual trans 4,5-cyclopropane in addition to iso methyl branching. However, the characterization of 1a in the sponge extract was done by gas chromatography-mass spectrometry on suitable volatile derivatives Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors maybe discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript followed by 1 H NMR of the total mixture of fatty acids. Therefore, a more rigorous confirmation of the structure of 1a is warranted. For this purpose, a total synthesis of 1a would not only serve to confirm the unusual trans cyclopropyl arrangement of the natural fatty acid, but also to report the total characterization of 1a, as well as to provide the necessary expertise to synthesize analogs for biological screening. Therefore, herein we report the first total synthesis of both the naturally occurring (±)-17-methyl-trans-4,5-methyleneoctadecanoic acid (1a) and the correspon...

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First total synthesis and antiprotozoal activity of (Z)-17-methyl-13-octadecenoic acid, a new marine fatty acid from the sponge Polymastia penicillus

Cited by 15 publications

References 13 publications

First total synthesis and antileishmanial activity of (Z)-16-methyl-11-heptadecenoic acid, a new marine fatty acid from the sponge Dragmaxia undata

First total synthesis and antileishmanial activity of (Z)-16-methyl-11-heptadecenoic acid, a new marine fatty acid from the sponge Dragmaxia undata

Acides gras inhabituels des organismes marins : une illustration de la biodiversité moléculaire marine

The first total synthesis of the (±)-17-methyl-trans-4,5-methyleneoctadecanoic acid and related analogs with antileishmanial activity

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