Total Synthesis of Cardiolipins Containing Chiral Cyclopropane Fatty Acids

2017 ◽  
Vol 82 (15) ◽  
pp. 7832-7838 ◽  
Author(s):  
Shinsuke Inuki ◽  
Ippei Ohta ◽  
Shunichi Ishibashi ◽  
Masayuki Takamatsu ◽  
Koichi Fukase ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Total Synthesis ◽  
Cyclopropane Fatty Acids

scholarly journals Enzymatic Synthesis of Cyclopropane Fatty Acids Catalyzed by Bacterial Extracts

1963 ◽  
Vol 238 (4) ◽  
pp. 1242-1248
Author(s):  
H. Zalkin ◽  
John H. Law ◽  
Howard Goldfine
Keyword(s):  
Fatty Acids ◽  
Enzymatic Synthesis ◽  
Cyclopropane Fatty Acids

scholarly journals First total synthesis of the (±)-2-methoxy-6-heptadecynoic acid and related 2-methoxylated analogs as effective inhibitors of the Leishmania topoisomerase IB enzyme

2012 ◽  
Vol 84 (9) ◽  
pp. 1867-1875 ◽  
Author(s):  
Néstor M. Carballeira ◽  
Michelle Cartagena ◽  
Fengyu Li ◽  
Zhongfang Chen ◽  
Christopher F. Prada ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Total Synthesis ◽  
Leishmania Donovani ◽  
Dna Topoisomerase ◽  
Triple Bonds ◽  
Weak Intermolecular Interactions ◽  
Topoisomerase Ib ◽  
Effective Inhibition ◽  
Acetylenic Fatty Acid

The fatty acids (±)-2-methoxy-6Z-heptadecenoic acid, (±)-2-methoxy-6-hepta-decynoic acid, and (±)-2-methoxyheptadecanoic acid were synthesized and their inhibitory activity against the Leishmania DNA topoisomerase IB enzyme (LdTopIB) determined. Both 2-OMe-17:1 fatty acids were synthesized from 4-bromo-1-pentanol, the olefinic fatty acid in 10 steps and in 7 % overall yield, while the acetylenic fatty acid in 7 steps and in 14 % overall yield. The 2-OMe-17:0 acid was prepared in 6 steps and in 42 % yield from 1-hexa-decanol. The 2-OMe-17:1 acids inhibited LdTopIB, with the acetylenic acid displaying an EC50 = 16.6 ± 1.1 μM, but the 2-OMe-17:0 acid did not inhibit LdTopIB. The (±)-2-methoxy-6Z-heptadecenoic acid preferentially inhibited LdTopIB over the human TopIB enzyme. Unsaturation seems to be a prerequisite for effective inhibition, rationalized in terms of weak intermolecular interactions between the active site of LdTopIB and either the double or triple bonds of the fatty acids. Toxicity toward Leishmania donovani promastigotes was also investigated, resulting in the order acetylenic > olefinic > saturated with the (±)-2-methoxy-6-heptadecynoic acid displaying an EC50 = 74.0 ± 17.1 μM. Our results indicate that α-methoxylation decreases the toxicity of C17:1 fatty acids toward L. donovani promastigotes, but improves their selectivity index.

scholarly journals Dietary fatty acids promote lipid droplet diversity through seipin enrichment in an ER subdomain

2018 ◽  
Author(s):  
Zhe Cao ◽  
Yan Hao ◽  
Yiu Yiu Lee ◽  
Pengfei Wang ◽  
Xuesong Li ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Lipid Droplet ◽  
Mammalian Cells ◽  
Dietary Fatty Acids ◽  
Fat Storage ◽  
Over Expression ◽  
C Elegans ◽  
Cyclopropane Fatty Acids ◽  
Host Metabolism

AbstractExogenous metabolites from microbial and dietary origins have profound effects on host metabolism. Here, we report that a sub-population of lipid droplets (LDs), which are conserved organelles for fat storage, is defined by metabolites-driven targeting of theC. elegansseipin ortholog, SEIP-1. Loss of SEIP-1 function reduced the size of a subset of LDs while over-expression of SEIP-1 had the opposite effect. Ultrastructural analysis revealed SEIP-1 enrichment in an endoplasmic reticulum (ER) subdomain, which co-purified with LDs. Analyses ofC. elegansand bacterial genetic mutants indicated a requirement of polyunsaturated fatty acids (PUFAs) and microbial cyclopropane fatty acids (CFAs) for SEIP-1 enrichment, as confirmed by dietary supplementation experiments. In mammalian cells, heterologous expression of SEIP-1 promoted lipid droplet expansion from ER subdomains in a conserved manner. Our results suggest that microbial and polyunsaturated fatty acids serve unexpected roles in regulating cellular fat storage by enforcing LD diversity.

Total Synthesis of DHA and DPAn-3 non-enzymatic oxylipins

Synthesis ◽  
2021 ◽  
Author(s):  
alexandre guy ◽  
Jérémy Merad ◽  
Thomas Degrange ◽  
Guillaume Reversat ◽  
Valérie Bultel-Poncé ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Docosahexaenoic Acid ◽  
Polyunsaturated Fatty Acids ◽  
Total Synthesis ◽  
Biological Properties ◽  
Chemical Structures ◽  
Structural Variety ◽  
Synthetic Strategy

Oxylipins are formed in-vivo from polyunsaturated fatty acids (PUFAs). A large structural variety of compounds is grouped under the term oxylipins, which differ from their formation mechanism (involving enzymes or not), as well as their chemical structures (cyclopentanes, tetrahydrofurans, hydroxylated-PUFA etc.). All structures of oxylipins are of great biological interests. Directly correlated to oxidative stress phenomenon, non-enzymatic oxylipins are used as systemic and/or specific biomarkers in various pathologies and more especially, they were found to have their own biological properties. Produced in-vivo as a non-separable mixture of isomers, total synthesis is a keystone to answer biological questions. In this work, we described the total synthesis of three non-enzymatic oxylipins derived from docosahexaenoic acid (DHA) and docosapentanoic acid (DPAn-3) using a unique and convergent synthetic strategy.

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