Chemoenzymatic synthesis of a focused library of enantiopure structured 1-O-alkyl-2,3-diacyl-sn-glycerol type ether lipids

Magnusson, Carlos D.; Gudmundsdottir, Anna V.; Haraldsson, Guđmundur G.

doi:10.1016/j.tet.2011.01.032

Cited by 21 publications

(40 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An efficient approach has been developed to prepare batyl, chimyl and selachyl alcohols enantiomerically pure (Magnusson et al, 2011) and as racemates (Halldorsson et al, 2004). The synthetic approach is shown in Scheme 2 for the synthesis of the naturally occurring (S)-batyl 3, (S)-chimyl 4 and (S)-selachyl 5 alcohols.…”

Section: Chemical Synthesismentioning

confidence: 99%

See 1 more Smart Citation

Ether lipids

Magnusson

Haraldsson

2011

Chemistry and Physics of Lipids

Self Cite

122

119

View full text Add to dashboard Cite

The naturally occurring 1-O-alkyl-sn-glycerols and their methoxylated congeners, 1-O-(2'-methoxyalkyl)-sn-glycerols, are biologically active compounds, ubiquitously found in nature as diacyl glyceryl ether lipids and phosphoether lipids. The chief objective of this article is to provide a comprehensive and up to date review on such ether lipids. The occurrence and distribution of these compounds in nature are extensively reviewed, their chemical structure and molecular variety, their biosynthesis and chemical synthesis and, finally, their various biological effects are described and discussed. An unprecedented biosynthesis of the 2'-methoxylated alkylglycerols is proposed. The first synthesis of enantiopure (Z)-(2'R)-1-O-(2'-methoxyhexadec-4'-enyl)-sn-glycerol, the most prevalent 2'-methoxylated type alkylglycerol present in cartilaginous fish, is described. It was accomplished by a highly convergent five step process.

show abstract

Section: Chemical Synthesismentioning

confidence: 99%

“…Full regiocontrol was offered by use of an immobilized Candida antarctica lipase that operated highly efficiently at room temperature. This has been extended to preparation of a focused library of such structured ether lipids (total of 72 compounds) possessing all even-numbered SFA ranging from C 2 -C 16 (Magnusson et al, 2011).…”

Section: Chemical Synthesismentioning

confidence: 99%

Ether lipids

Magnusson

Haraldsson

2011

Chemistry and Physics of Lipids

Self Cite

122

119

View full text Add to dashboard Cite

show abstract

“…To a solution of 1‐ O ‐hexadecyl‐ sn ‐glycerol ( S )‐ 1 (100 mg, 0.32 mmol), DMAP (71 mg, 0.63 mmol), and EDCI (182 mg, 0.95 mmol) in dry dichloromethane (3 mL) was added EPA as free acid (210 mg, 0.69 mmol) and the resulting solution stirred at 35°C under nitrogen atmosphere. TLC was used to monitor the progress of the reaction with diethyl ether/petroleum ether (5:95) as eluent.…”

Section: Methodsmentioning

confidence: 99%

“…That work was extended to a focused library of similarly structured TAGs covering all saturated even carbon number fatty acids including C2 to C16:0 . This was further extended to the enantiopure diacylglyceryl ethers (DAGEs) of the 1‐O‐alkyl‐ sn ‐glycerol type with the pure saturated even carbon number fatty acids located at the terminal sn ‐3 position of the glycerol backbone along with pure EPA or DHA at the sn ‐2 position . And, more recently, the focused library was further expanded to include reversed structured TAGs and DAGEs , this time possessing the pure EPA and DHA acyl groups at the terminal positions with the saturated fatty acyl groups located at the 2‐position of the glycerol framework.…”

Section: Introductionmentioning

confidence: 99%

Lipids from the marine world: Perspectives of an organic chemist

Rögnvaldsdóttir

Magnusson

Haraldsson

2017

Euro J Lipid Sci & Tech

Self Cite

View full text Add to dashboard Cite

This report describes synthesis of novel structured triacylglycerols (TAGs) and diacylglyceryl ethers (DAGEs) of the 1‐O‐alkyl‐sn‐glycerol type constituting EPA and DHA as the sole fatty acids. One of two TAGs was comprised of a pure EPA located at the 1,3‐positions with pure DHA at the 2‐position and the other had it reversed with a pure DHA at the 1,3‐positions and pure EPA at the 2‐positions. The similarly structured DAGEs were derived from chimyl‐, batyl‐, and selachyl alcohols constituting pure EPA at their sn‐3 position with pure DHA at the sn‐2 position as well as the opposite composition with pure DHA at the sn‐3 position and EPA at the sn‐2 position, the total of six such DAGE products. The syntheses of these compounds were brought about by a two‐step chemoenzymatic process involving a highly regioselective immobilized Candida antarctica lipase to incorporate EPA or DHA activated as acetoxime esters exclusively into the 1,3‐positions of glycerol and the sn‐3 position of the 1‐O‐alkyl‐sn‐glycerols. The second PUFA acyl groups were subsequently introduced to the remaining 2‐positions by EDCI coupling agent to accomplish the title compounds highly efficiently in very high to excellent yields (86–92%). Practical applications: The work described is based on a previously reported methodology to introduce n‐3 PUFAs activated as oxime esters exclusively into the terminal 1,3‐positions of glycerol and 1‐O‐alkyl‐sn‐glycerols to prepare reversed structured TAGs and DAGEs by use of immobilized Candida antarctica lipase. The methodology is ideal for introducing isotopically labeled fatty acids into predetermined positions of TAGs and DAGEs. Novel structured triacylglycerols (TAGs) and diacylglyceryl ethers (DAGEs), constituting EPA and DHA as the sole fatty acids, were obtained by a two‐step chemoenzymatic synthesis comprised of an exclusive incorporation of EPA or DHA, activated as acetoxime esters, into the terminal positions of glycerol and 1‐O‐alkyl‐sn‐glycerols by use of immobilized Candida antarctica lipase, and a subsequent introduction of a second PUFA acyl group to the remaining 2‐positions by EDCI coupling agent.

show abstract

“…This method was extended to the preparation of a focused library of eight monoacyl intermediate adducts for all evennumbered SFAs ranging from C 2 -C 16 and the corresponding EPA and DHA structured diacyl glycerol ethers products for chimyl, batyl and selachyl alcohols, giving a total of 72 compounds. 10 The solution-phase parallel synthesis and screening of anti-tumour activities from fenbufen and ethacrynic acid libraries have been investigated. The compounds were derivatised with 1-amino-4-azidobutane, and subsequently coupled with 102 carboxylic acids to give amide products.…”

Section: Library Applicationsmentioning

confidence: 99%

Combinatorial Chemistry Online

Terrett

2011

Combinatorial Chemistry - an Online Journal

View full text Add to dashboard Cite

Chemoenzymatic synthesis of a focused library of enantiopure structured 1-O-alkyl-2,3-diacyl-sn-glycerol type ether lipids

Cited by 21 publications

References 29 publications

Ether lipids

Ether lipids

Lipids from the marine world: Perspectives of an organic chemist

Combinatorial Chemistry Online

Contact Info

Product

Resources

About