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First stereoselective total synthesis of 4(S),5(S)-oxido-17(S)-hydroxy-6(E),8(E),10(Z),13(Z),15(E),19(Z)-docosahexaenoic acid, the biosynthetic precursor of resolvins D3 and D4.

ABSTRACT: The first total convergent synthesis of 4(S),5(S)-oxido-17(S)-hydroxy-6(E),8(E),10(Z),13(Z),15(E),19(Z)-docosahexaenoic acid (1) is described. The reported synthesis led to confirmation of the native epoxydocosahexaenoic acid as the biosynthetic precursor of lipid mediators resolvin D3 and resolvin D4. These potent enzymatic products of docosahexaenoic acid (DHA) are important signaling molecules in the resolution of inflammation. A stereocontrolled and chiral pool-based synthetic strategy was employed, with key features including epoxide transposition under basic conditions to form the oxirane ring, and a cis-selective Wittig reaction to secure the target docosahexaenoate backbone.

SUBMITTER: Nshimiyimana R

PROVIDER: S-EPMC9015894 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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First stereoselective total synthesis of 4(S),5(S)-oxido-17(S)-hydroxy-6(E),8(E),10(Z),13(Z),15(E),19(Z)-docosahexaenoic acid, the biosynthetic precursor of resolvins D3 and D4.

Nshimiyimana Robert R Lam Ting Fung TF Aggarwal Shubhangi S Serhan Charles N CN Petasis Nicos A NA

RSC advances 20220419 19

The first total convergent synthesis of 4(S),5(S)-oxido-17(S)-hydroxy-6(E),8(E),10(Z),13(Z),15(E),19(Z)-docosahexaenoic acid (1) is described. The reported synthesis led to confirmation of the native epoxydocosahexaenoic acid as the biosynthetic precursor of lipid mediators resolvin D3 and resolvin D4. These potent enzymatic products of docosahexaenoic acid (DHA) are important signaling molecules in the resolution of inflammation. A ...[more]

PMID: 35481084

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