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A Sequential Umpolung/Enzymatic Dynamic Kinetic Resolution Strategy for the Synthesis of γ-Lactones.

ABSTRACT: Combining biological and small-molecule catalysts under a chemoenzymatic manifold presents a series of significant advantages to the synthetic community. We report herein the successful development of a two-step/single flask synthesis of γ-lactones through the merger of Umpolung catalysis with a ketoreductase-catalyzed dynamic kinetic resolution, reduction, and cyclization. This combined approach delivers highly enantio- and diastereoenriched heterocycles and demonstrates the feasibility of integrating NHC catalysis with enzymatic processes.

SUBMITTER: Maskeri MA

PROVIDER: S-EPMC7210063 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Direct Catalytic Asymmetric Synthesis of Trifluoromethylated γ-Amino Esters/Lactones via Umpolung Strategy.

Project description:Enabled by the discovery of new cinchonium salts and coadditives, a direct and efficient asymmetric access to trifluoromethylated γ-amino esters/lactones has been realized through the enantioselective and diastereoselective umpolung reaction of trifluoromethyl imines with acrylates or α,β-unsaturated lactones as carbon electrophiles. At 0.5-5.0 mol % catalyst loadings, the newly developed catalytic system activates a variety of imine substrates as unconventional nucleophiles to mediate highly chemo-, regio-, diastereo-, and enantioselective C-C bond forming reactions. The developed synthetic protocol represents an excellent strategy to target a series of versatile and enantiomerically enriched γ-amino esters/lactones in good to excellent yields from the readily available starting materials. Additionally, we found that the epi-vinyl catalysts based on cinchonidine and quinine promote a similarly high enantioselective reaction generating the opposite configuration of chiral products in a highly efficient manner, which allows convenient access to either the R- or S-enantiomer of the chiral amine products in high yields and excellent enantioselectivities.

| S-EPMC6467775 | biostudies-literature

Chemoenzymatic Synthesis of trans-?-Aryl-?-hydroxy-?-lactones and Enzymatic Kinetic Resolution of Their Racemic Mixtures.

Project description:Two novel and convenient routes to obtain enantiomerically enriched trans-?-aryl-?-hydroxy-?-lactones 5a-d with potential antifeedant and anticancer activity were developed. In the first method starting from corresponding enantiomers of ?,?-unsaturated esters 4a-d derived from enzymatically resolved allyl alcohols 1a-d, both enantiomers of hydroxylactones 5a-d were synthesized with high enantiomeric excesses (73%-97%). Configurations of the stereogenic centers of the synthesized compounds were assigned based on the mechanism of acidic lactonization of esters 4a-d in the presence of m-chloroperbenzoic acid (m-CPBA). An alternative method for the production of optically active trans-?-aryl-?-hydroxy-?-lactones 5a-d was lipase-catalyzed kinetic resolution of their racemic mixtures by transesterification with vinyl propionate as the acyl donor. The most efficient enzyme in the screening procedure was lipase B from Candida antarctica. Its application on a preparative scale after 6 h afforded unreacted (+)-(4S,5R,6S)-hydroxylactones 5a-d and (+)-(4R,5S,6R)-propionates 6a-d, most of them with high enantiomeric excesses (92%-98%). Resolution of lactone 5d with bulky 1,3-benzodioxol ring provided products with significantly lower optical purity (ee = 89% and 84% for hydroxylactone 5d and propionate 6d, respectively). The elaborated methods give access to both enantiomers of trans-?-aryl-?-hydroxy-?-lactones 5a-d with the defined absolute configurations of stereogenic centers, which is crucial requirement for the investigations of relationship: spatial structure-biological activity.

| S-EPMC6272857 | biostudies-other

Reductive enzymatic dynamic kinetic resolution affording 115 g/L (S)-2-phenylpropanol.

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| S-EPMC8507385 | biostudies-literature

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| S-EPMC9159106 | biostudies-literature

Kinetic Resolution of Alkylidene Norcamphors via a Ligand-Controlled Umpolung-Type 1,3-Dipolar Cycloaddition.

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| S-EPMC6317281 | biostudies-literature

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| S-EPMC8319157 | biostudies-literature

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| S-EPMC6501835 | biostudies-literature

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