Novel Cyclopropane Fatty Acids from the Phospholipids of the Caribbean Sponge <i>Pseudospongosorites suberitoides</i>

Carballeira, Néstor M.; Montano, Nashbly; Vicente, Jan; Rodrı́guez, Abimael D.

doi:10.1007/s11745-007-3047-3

Cited by 26 publications

(20 citation statements)

References 25 publications

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“…With both acids 1a and 1b at hand we were in a good position to unequivocally corroborate the relative trans cyclopropane stereochemistry as well as the structure of the natural fatty acid 1a that was assigned on the basis of 1 H-NMR spectroscopy on the whole fatty acid mixture from the sponge P. suberitoides 3. This was done by gas chromatographic co-injection of the corresponding methyl esters of 1a and 1b , prepared from the acids by esterification with MeOH and catalytic amounts of HCl, with the fatty acid methyl ester mixture from the phospholipids of the sponge P. suberitoides 3.…”

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confidence: 56%

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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confidence: 56%

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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“…As to the origin of 1a – 1b we can speculate that the biosynthetic pathways i -15:0 → i -27:0 → i -5,9–27:2 → 2-OH- i -5,9–27:2 → 2-OMe- i -5,9–27:2 and ai -15:0 → ai -27:0 → ai -5,9–27:2 → 2-OH- ai -5,9–27:2 → 2-OMe- ai -5,9–27:2 might be operative in A. niger , which can explain the need for the accumulation of the methyl-branched short precursors. Despite the fact that the methyl branched i -5,9–27:2 and ai -5,9–27:2 FA have been isolated from several sponges [6,7], this is the first time that their 2-methoxylated analogs have been identified in a sponge.…”

Section: Discussionmentioning

confidence: 99%

“…For example, the 22-Me-5,9–24:2 and the unusual 23-Me-5,9–24:2 were identified in the lipid extract of the sponge Geodinella robusta [4], the 23-Me-5,9–25:2 was initially identified in the sponge Cribrochalina vasculum [5], while the 25-Me-5,9–26:2 and the 24-Me-5,9–26:2 were first identified in the sponge Petrosia ficiformis [6] and most recently in the Caribbean sponge Pseudospongosorites suberitoides [7]. All of these iso / anteiso Δ5,9 FA have, as a common biosynthetic precursor, either iso -15:0 and/or anteiso -15:0 that are also typically found in sponges but that definitively originate from bacterial symbionts within the sponge [8].…”

Section: Introductionmentioning

confidence: 99%

Novel Very Long‐Chain α‐Methoxylated Δ5,9 Fatty Acids from the Sponge Asteropus niger Are Effective Inhibitors of Topoisomerases IB

Carballeira

Montano

Amador

et al. 2015

Lipids

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The novel fatty acids (2R,5Z,9Z)-2-methoxy-25-methyl-5,9-hexacosadienoic acid (1a) and (2R,5Z,9Z)-2-methoxy-24-methyl-5,9-hexacosadienoic acid (1b) were isolated in 80% purity from the Caribbean sponge Asteropus niger by chloroform/methanol extraction followed by solvent partitioning and silica gel column chromatography. The compounds were characterized by utilizing a combination of gas chromatography-mass spectrometry, nuclear magnetic resonance, and circular dichroism. Acids 1a and 1b were not detected in the phospholipids (PtdCho and PtdIns) of the sponge, but rather as free FA and possibly in glycosylceramides. The mixtures of 1a and 1b displayed cytotoxicity towards THP-1 and HepG2 cells with EC50’s between 41 and 35 μg/mL. Apoptosis was not the preferred mode of cell death induced by 1a–1b in the THP-1 cells. This implies other types of cytotoxicity mechanisms, such as membrane disruption and/or the inhibition (EC50 = 1.8 μg/mL) of the human topoisomerase IB enzyme (hTopIB), with a mechanism of inhibition different from the one displayed by camptothecin (CPT). In a separate experiment, the mixture of 1a and 1b also displayed cytotoxicity towards ex vivo mouse splenocytes infected with Leishmania infantum amastigotes (IC50 = 0.17 mg/mL) and free living promastigotes (IC50 = 0.34 mg/mL). It was also found that the FA were inhibitory of the Leishmania topoisomerase IB (LTopIB) with an EC50 = 5.1 μg/mL. Taken together, 1a and 1b represent a new class of FA with potential as TopIB inhibitors that preferentially inhibit hTopIB over LTopIB.

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“…It has not yet been recorded from tunicates. Cyclopropane FA were observed in marine invertebrates such as sponges [50,55], and it is known that they are widely distributed among both Gram-positive and Gram-negative bacteria [56].…”

Section: Discussionmentioning

confidence: 99%

Phospholipid Distribution and Phospholipid Fatty Acids of the Tropical Tunicates Eudistoma sp. and Leptoclinides uniorbis

Dagorn

Dumay

Wielgosz‐Collin

et al. 2010

Lipids

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Two tunicates, Eudistoma sp. and Leptoclinides uniorbis, collected from the tropical waters off Djibouti were investigated for lipids and phospholipid (PL) fatty acids. PL accounted for 38.2% of the total lipids in Eudistoma sp. and for 30.2% in L. uniorbis. PL classes were quantified by normal-phase high-performance liquid chromatography using an evaporative light-scattering detector and revealed essential differences. Eudistoma sp. contained mainly phosphatidylcholine (PC, 70.3% of total PL) and lysophosphatidylcholine (LPC, 11.9%) and was devoid of phosphatidylserine (PS), whereas the major PL of L. uniorbis was PS (59.1%) followed by PC (22.5%) and LPC (8.8%). Gas chromatography-mass spectrometry analyses of fatty acid (FA) derivatives revealed 38 FA in Eudistoma sp., and 35 FA in L. uniorbis, ranged from C(12) to C(24) chain lengths. Polyunsaturated FA accounted for 25.9% in Eudistoma sp. and for 32.3% in L. uniorbis. Interestingly, L. uniorbis contained a high percentage (16.7%) of the 20:5n-3 acid (8.9% in Eudistoma sp.) and the 18:4n-3 acid (4.1%). Significant levels of the 20:4n-6 acid were observed in both organisms (7.8 and 6.0% respectively). Eudistoma sp. contained the rare 20:3n-7 acid (2.3%) only recorded to date in hydrothermal vent animals. The cyclopropane dihydrosterculic acid was identified in both tunicates (0.7 and 0.5% respectively). These latter FA, together with some unusual branched saturated and monounsaturated FA, revealed the occurrence of associated bacteria in the tunicates. Another noticeable feature was a series of eight C(16) to C(18) aldehyde dimethylacetals revealing the presence of plasmalogens at 5.0% in Eudistoma sp. and 14.2% in L. uniorbis. The results of this study were compared with those previously published for other tunicates regarding mainly PL content and FA composition.

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Novel Cyclopropane Fatty Acids from the Phospholipids of the Caribbean Sponge Pseudospongosorites suberitoides

Cited by 26 publications

References 25 publications

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

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

Novel Very Long‐Chain α‐Methoxylated Δ5,9 Fatty Acids from the Sponge Asteropus niger Are Effective Inhibitors of Topoisomerases IB

Phospholipid Distribution and Phospholipid Fatty Acids of the Tropical Tunicates Eudistoma sp. and Leptoclinides uniorbis

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