78144-19-1

Usage

InChI:InChI=1/C22H31IO2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-20(23)21-18-19-22(24)25-21/h3-4,6-7,9-10,12-13,15-16,20-21H,2,5,8,11,14,17-19H2,1H3/b4-3+,7-6+,10-9+,13-12+,16-15+

Upstream product

• 6217-54-5 docosahexaenoic acid 
• 81926-94-5 all-(Z)-ethyl 4,7,10,13,16,19-docosahexaenoate 

Downstream Products

• 845673-68-9 5-[(3Z,6Z,9Z,12Z,15Z)-1-hydroxyoctadeca-3,6,9,12,15-pentaenyl]dihydro-2(3H)-furanone 
• 121818-29-9 methyl 3-(3-((2Z,5Z,8Z,11Z,14Z)-heptadeca-2,5,8,11,14-pentaen-1-yl)oxiran-2-yl)propanoate 
• 6217-54-5 docosahexaenoic acid 
• 51592-59-7 all-cis-3,6,9,12,15-octadecapentaenoic acid 
• 845673-74-7 (5E,7Z,10Z,13Z,16Z,19Z)-4-oxodocosa-5,7,10,13,16,19-hexaenoic acid 
• 90906-40-4 (5E,7Z,10Z,13Z,16Z,19Z)-4-Hydroxy-5,7,10,13,16,19-docosahexaenoic acid 

Relevant academic research and scientific papers

Identification of putative metabolites of docosahexaenoic acid as potent PPARγ agonists and antidiabetic agents

We found that putative metabolites of docosahexaenoic acid (DHA) are strong PPARγ activators and potential antidiabetic agents. We designed DHA derivatives based on the crystal structure of PPARγ, synthesized them and evaluated their activities in vitro and in vivo. The efficacy of 5E-4-hydroxy-DHA 2a as a PPARγ activator was about fourfold stronger than that of pioglitazone. Furthermore, the 4-keto derivative (10b) showed antidiabetic activity in animal models without producing undesirable effects such as obesity and hepatotoxicity.

PROCESSES IN THE PREPARATION OF POLYUNSATURATED KETONE COMPOUNDS

A process comprising the following steps: a-i) treating a polyunsaturated ester with a base in a solvent of lower alcohol and water to form the corresponding polyunsaturated acid; a-ii) treating the product from step a-i), especially the crude product, with a halolactonization agent in the solvent of lower alcohol and water, to form the corresponding polyunsaturated halolactone; and a-iii) treating the product from step a-ii), especially the crude product, with a reagent in the solvent of lower alcohol and water to convert the polyunsaturated halolactone to the corresponding polyunsaturated epoxide lower alkyl ester.

Control Mechanism for Carbon-Chain Length in Polyunsaturated Fatty-Acid Synthases

Polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are essential fatty acids. PUFA synthases are composed of three to four subunits and each create a specific PUFA without undesirable byproducts. However, detailed biosynthetic mechanisms for controlling final product profiles have been obscure. Here, the bacterial DHA and EPA synthases were carefully dissected by in vivo and in vitro experiments. In vitro analysis with two KS domains (KSA and KSC) and acyl-acyl carrier protein (ACP) substrates showed that KSA accepted short- to medium-chain substrates while KSC accepted medium- to long-chain substrates. Unexpectedly, condensation from C18 to C20, the last elongation step in EPA biosynthesis, was catalyzed by KSA domains in both EPA and DHA synthases. Conversely, condensation from C20 to C22, the last elongation step for DHA biosynthesis, was catalyzed by the KSC domain in DHA synthase. KSC domains therefore determine the chain lengths.

Synthesis, molecular modelling studies and biological evaluation of new oxoeicosanoid receptor 1 agonists

The oxoeicosanoid receptor 1 (OXER1) is a member of the G-protein coupled receptors (GPCR) family, and is involved in inflammatory processes and oncogenesis. As such it is an attractive target for pharmacological intervention. The present study aimed to shed light on the molecular fundaments of OXER1 modulation using chemical probes structurally related to the natural agonist 5-oxo-ETE. In a first step, 5-oxo-ETE and its closely related derivatives (5-oxo-EPE and 4-oxo-DHA) were obtained by conducting concise and high-yielding syntheses. The biological activity of obtained compounds was assessed in terms of potency (EC50) and efficacy (Emax) for arrestin recruitment. Finally, molecular modelling and simulation were used to explore binding characteristics of 5-oxo-ETE and derivatives with the aim to rationalize biological activity. Our data suggest that the tested 5-oxo-ETE derivatives (i) insert quickly into the membrane, (ii) access the receptor via transmembrane helices (TMs) 5 and 6 from the membrane side and (iii) drive potency and efficacy by differential interaction with TM5 and 7. Most importantly, we found that the methyl ester of 5-oxo-ETE (1a) showed even a higher maximum response than the natural agonist (1). In contrast, shifting the 5-oxo group into position 4 results in inactive compounds (4-oxo DHA compounds (3) and (3a)). All in all, our study provides relevant structural data that help understanding better OXER1 functionality and its modulation. The structural information presented herein will be useful for designing new lead compounds with desired signalling profiles.

Construction of a series of intermediates in the β-oxidation pathway from THA to EPA via DHA in free acid form

β-Oxidation of most fatty acids occurs in the mitochondria. However, β-oxidation for ω-3 polyunsaturated fatty acids (PUFAs) is distinct from abundant fatty acids and occurs in the peroxisomes. Since little is known about peroxisomal β-oxidation, here we report the synthesis of proposed intermediates of ω-3 PUFA β-oxidation steps in free fatty acid form having a conjugated double bond, a β-hydroxyl group, a β-olefin and a β-carbonyl group. These fatty acids can serve as authentic samples for biological experiments.

Synthesis of all-Z-1,6,9,12,15-octadecapenten-3-one, a vinyl ketone polyunsaturated marine natural product isolated from callysponga sp

The synthesis of the marine natural product 1,6Z,9Z,12Z,15Z- octadecapentaen- 3-one (1) has been achieved by two different routes starting from the ethyl esters of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively. Using EPA ethyl ester as starting material the polyunsaturated vinyl ketone lipid 1 was obtained in 17% overall yield.

Synthesis of docosahexaenoic acid derivatives designed as novel PPARγ agonists and antidiabetic agents

To discover novel peroxisome proliferator-activated receptor γ (PPARγ) agonists that could be used as antidiabetic agents, we designed docosahexaenoic acid (DHA) derivatives (2 and 3), which have a hydrophilic substituent at the C(4)-position, based on the crystal structure of the ligand-binding pocket of PPARγ. These compounds were synthesized via iodolactone as a key intermediate. We found that both DHA derivatives (2 and 3) showed PPARγ transactivation higher than, or comparable to, that of pioglitazone, which is a TZD derivative used as an antidiabetic agent. DHA derivatives related to these potent compounds 2 and 3 were also synthesized to study structure-activity relationships. Furthermore, 4-OH DHA 2, which shows strong PPARγ transcriptional activity, was separated as an optically pure form.

Synthesis of polyconjugated fatty acids

The present invention relates to fatty acids. In particular, the present invention provides polyconjugated fatty acids, and methods of their synthesis and their use.

Syntheses of some polyunsaturated sulfur- and oxygen-containing fatty acids related to eicosapentaenoic and docosahexaenoic acids.

With the aim of enhancing selectively the beneficial biological effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) a number of polyunsaturated fatty acids containing sulfur or oxygen atoms in the chain has been synthesized starting from EPA and DHA, respectively. Oxidative degradation of these acids led to the corresponding aldehydes all-(Z)-3,6,9,12-pentadecatetraenal and all-(Z)-3,6,9,12,15-octadecapentaenal. Reactions with DBU converted these aldehydes quantitatively into the conjugated isomers (2E,6Z,9Z,12Z)-pentadecatetraenal and (2E,6Z,9Z,12Z,15Z)-octadecapentaenal, respectively. The four aldehydes were transformed by a sequence of reactions comprising reduction to the alcohols, halogenation and substitution with mercapto esters into the corresponding sulfur containing polyunsaturated fatty acid esters. The oxygen containing esters were prepared from the respective alcohol by boron trifluoride catalysed reaction with ethyl diazoacetate.

ALL-CIS-3,6,9,12,15-OCTADECAPENTAENOIC ACID FROM THE UNICELLULAR ALGA GYMNODINIUM KOWALEVSKII

All-cis-3,6,9,12,15-octadecapentaenoic acid (18:5n-3) was isolated from total lipids of the cultivated microalga Gymnodinium kowalevskii.Its structure was confirmed by GC-MS, 1HNMR, IR and synthesis using a modified method of iodolactonization from 22:6n-3. Key Word Index - Gymnodinium kowalevskii; Gymnodiniaceae; unicellular algae; marine lipids; octadecapentaenoic acid; synthesis.