Enantioselective synthesis of alpha-quaternary amino acid derivatives by sequential enzymatic desymmetrization and Curtius rearrangement of alpha,alpha-disubstituted malonate diesters

The Journal of Organic Chemistry
Violeta IosubThomas G Back

Abstract

A convenient and versatile enantioselective synthesis of biologically important alpha-quaternary amino acid derivatives was based on the sequential double alkylation or arylation of dimethyl malonate, followed by desymmetrization with porcine liver esterase (PLE) and Curtius rearrangement. The PLE-mediated hydrolysis of the prochiral dialkylated malonate diesters produced the corresponding chiral half-esters in high yield and with enantiomeric excesses of 43% to >98%. Curtius rearrangement of the latter products, after trapping of the intermediate isocyanates with benzyl alcohol or amines, afforded the corresponding Cbz-protected amino esters or ureas. The absolute configurations of the major products in five examples were established by conversion to compounds with known specific rotations, or by X-ray crystallography of derivatives obtained with chiral amines of known configuration.

References

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Sep 29, 2007·Angewandte Chemie·Anke HummelUwe T Bornscheuer
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Citations

Jan 28, 2020·Chemical Communications : Chem Comm·Wei-Xin KongWei-Liang Duan
Jul 9, 2011·Organic & Biomolecular Chemistry·Abdelatif ElMarrouniMontserrat Heras
Jan 9, 2018·Journal of the American Chemical Society·Pei GanScott A Snyder
Apr 30, 2011·Chemical Reviews·Eduardo García-UrdialesVicente Gotor
May 6, 2015·The Journal of Organic Chemistry·Varun KumarAigars Jirgensons
Sep 14, 2017·The Journal of Organic Chemistry·Maheswara Rao GokadaSophie Rees-Jones
Sep 19, 2017·Journal of the American Chemical Society·Marc LinigerBrian M Stoltz
Jan 12, 2021·Journal of the American Chemical Society·J Henry BlackwellMatthew J Gaunt
Sep 23, 2021·Journal of the American Chemical Society·J Henry BlackwellMatthew J Gaunt

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