Enzymatic kinetic resolution of Morita-Baylis-Hillman acetates

Juma, Wanyama P.; Chhiba, Varsha; Brady, Dean; Bode, Moira L.

doi:10.1016/j.tetasy.2017.08.001

Cited by 5 publications

(8 citation statements)

References 26 publications

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“…Because of both our ongoing studies with PUFAs and the many reported bioactivities of DHA and EDPs, we sought an operationally simple and cost-effective method to access both enantiomers of two EDP regioisomers, 16,17-and 19,20-EDP, without recourse to total synthesis or chiral separations. Enzymatic synthesis has become a popular method to access both single enantiomers of molecules and compounds that are otherwise difficult to prepare by conventional synthetic means and have been used successfully in esterifications (40), glycosylations (41), aldol reactions (42), and kinetic resolutions (43) and have even been used on an industrial scale (44). Enzymes are operationally simple to use, have fast reaction times, use mild conditions, and are environmentally benign (aqueous reactions; lack of heavy metal catalysts or toxic solvents).…”

Section: Discussionmentioning

confidence: 99%

Enzymatic synthesis and chemical inversion provide both enantiomers of bioactive epoxydocosapentaenoic acids

Cinelli

Yang

Scharmen

et al. 2018

Journal of Lipid Research

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Epoxy PUFAs are endogenous cytochrome P450 (P450) metabolites of dietary PUFAs. Although these metabolites exert numerous biological effects, attempts to study their complex biology have been hampered by difficulty in obtaining the epoxides as pure regioisomers and enantiomers. To remedy this, we synthesized 19,20- and 16,17-epoxydocosapentaenoic acids (EDPs) (the two most abundant EDPs in vivo) by epoxidation of DHA with WT and the mutant (F87V) P450 enzyme BM3 from WT epoxidation yielded a 4:1 mixture of 19,20:16,17-EDP exclusively as (,) enantiomers. Epoxidation with the mutant (F87V) yielded a 1.6:1 mixture of 19,20:16,17-EDP; the 19,20-EDP fraction was ∼9:1 (,):(,), but the 16,17-EDP was exclusively the (,) enantiomer. To access the (,) enantiomers of these EDPs, we used a short (four-step) chemical inversion sequence, which utilizes 2-(phenylthio)ethanol as the epoxide-opening nucleophile, followed by mesylation of the resulting alcohol, oxidation of the thioether moiety, and base-catalyzed elimination. This short synthesis cleanly converts the (,)-epoxide to the (,)-epoxide without loss of enantiopurity. This method, also applicable to eicosapentaenoic acid and arachidonic acid, provides a simple, cost-effective procedure for accessing larger amounts of these metabolites.

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Section: Discussionmentioning

confidence: 99%

Enzymatic synthesis and chemical inversion provide both enantiomers of bioactive epoxydocosapentaenoic acids

Cinelli

Yang

Scharmen

et al. 2018

Journal of Lipid Research

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“…Hence, hydrolases such as lipases can now be considered mainstream organic synthetic tools, and their popularity continues unabated. [94][95][96] Research is being directed increasingly to adapting the enzymes for industrial applications. 53,97 Up until fairly recently it was generally thought that kinetic resolutions would be dominated by biocatalytic processes and asymmetric syntheses would be largely the domain of precious metal complexes with chiral ligands as catalysts in reactions such as asymmetric hydrogenations and hydroformylations.…”

Section: Hydrolytic Processesmentioning

confidence: 99%

The Hitchhiker's guide to biocatalysis: recent advances in the use of enzymes in organic synthesis

2020

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“…Absolute stereochemistry was not determined, but the optical rotation of all the alcohol products 23 was found to be (+), which for the benzaldehyde derivative (Ar=Ph) corresponds to the (S)alcohol. [76] When these authors conducted similar reactions on aromatic MBH adducts derived from methyl acrylate, they obtained poor enantioselectivities (46-65 %) using PLAP (Scheme 14). In each case, the major alcohol 24 obtained from hydrolysis was dextrorotatory (+), which for Ar=Ph corresponds to the (S)alcohol.…”

Section: Use Of Lipasesmentioning

confidence: 99%

The Application of Biocatalysis in the Preparation and Resolution of Morita‐Baylis‐Hillman Adducts and Their Derivatives

et al. 2021

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The Morita-Baylis-Hillman (MBH) reaction affords highly functionalised allylic alcohols containing a new stereogenic centre. These MBH adducts are very versatile and have been transformed into a large range of products, some of which have medicinal potential. Several examples of asymmetric syntheses of MBH adducts have been reported, although a generally applicable method remains to be developed. Biocatalytic approaches for the synthesis and enzymatic kinetic resolution of MBH adducts have been reported, and are discussed in detail in this review. Enzymes able to catalyse the asymmetric MBH reaction have been identified, but selectivity and efficiency have generally been low. Lipases, esterases and nitrile-converting enzymes have all been successfully applied in the resolution of MBH adducts, with excellent selectivity being realised in most cases.

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Enzymatic kinetic resolution of Morita-Baylis-Hillman acetates

Cited by 5 publications

References 26 publications

Enzymatic synthesis and chemical inversion provide both enantiomers of bioactive epoxydocosapentaenoic acids

Enzymatic synthesis and chemical inversion provide both enantiomers of bioactive epoxydocosapentaenoic acids

The Hitchhiker's guide to biocatalysis: recent advances in the use of enzymes in organic synthesis

The Application of Biocatalysis in the Preparation and Resolution of Morita‐Baylis‐Hillman Adducts and Their Derivatives

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