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Facile and Stereoselective Synthesis of (Z)-15-Octadecenoic Acid and (Z)-16-Nonadecenoic Acid: Monounsaturated Omega-3 Fatty Acids

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Lipids

Abstract

Facile syntheses of the monounsaturated omega-3 fatty acids, (Z)-15-octadecenoic acid and (Z)-16-nonadecenoic acid, are presented. Commercially available hydroxy fatty acids were esterified and oxidised, followed by the Wittig reaction to introduce the omega-3 olefinic bond; hydrolysis yielded the omega-3 fatty acids in high purity. An examination of different reaction conditions for the Wittig step found that THF as solvent and coupling temperatures of −78 °C gave optimal stereoselectivity, affording the omega-3 olefins in Z:E ratios ≥97:3. The syntheses have overall yields of ~43%, and utilise straightforward, robust chemistry, that may be readily scaled up and reproduced. Also presented is a method for accurately determining the double bond geometry and isomeric purity of the fatty acid products using 1H–13C-HSQC NMR and GC–MS, respectively.

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Fig. 1
Scheme 1

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Abbreviations

DCM:

Dichloromethane

DMF:

N,N-dimethylformamide

FAME:

Fatty acid methyl ester

NaN(TMS)2 :

Sodium bis(trimethylsilyl)amide

PCC:

Pyridinium chlorochromate

PUFA:

Polyunsaturated fatty acid

THF:

Tetrahydrofuran

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Acknowledgments

The present work was supported by a grant from the Australian National Health and Medical Research Council. The authors wish to acknowledge Bruce Tattam for his expertise and assistance with the GC–MS analysis.

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Authors and Affiliations

  1. Pharmacogenomics and Drug Development Group, Faculty of Pharmacy A15, University of Sydney, Sydney, NSW, 2006, Australia

    Tristan Rawling, Pei H. Cui & Michael Murray

  2. Pharmaceutical Chemistry, Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia

    Colin C. Duke

Authors
  1. Tristan Rawling
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  2. Colin C. Duke
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  3. Pei H. Cui
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  4. Michael Murray
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Correspondence to Tristan Rawling.

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Rawling, T., Duke, C.C., Cui, P.H. et al. Facile and Stereoselective Synthesis of (Z)-15-Octadecenoic Acid and (Z)-16-Nonadecenoic Acid: Monounsaturated Omega-3 Fatty Acids. Lipids 45, 159–165 (2010). https://doi.org/10.1007/s11745-009-3378-3

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