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Transaminase-Catalyzed Synthesis of ß-Branched Noncanonical Amino Acids Driven by a Lysine Amine Donor.
Dunham, Noah P; Winston, Matthew S; Ray, Ritwika; Eberle, Claire M; Newman, Justin A; Gao, Qi; Cao, Yang; Barrientos, Rodell C; Ji, Yining; Reibarkh, Mikhail Y; Silverman, Steven M.
Afiliação
  • Dunham NP; Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Winston MS; Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Ray R; Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Eberle CM; Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Newman JA; Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Gao Q; Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Cao Y; Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Barrientos RC; Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Ji Y; Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Reibarkh MY; Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Silverman SM; Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
J Am Chem Soc ; 146(23): 16306-16313, 2024 Jun 12.
Article em En | MEDLINE | ID: mdl-38804633
ABSTRACT
Transaminases are choice biocatalysts for the synthesis of chiral primary amines, including amino acids bearing contiguous stereocenters. In this study, we employ lysine as a "smart" amine donor in transaminase-catalyzed dynamic kinetic resolution reactions to access ß-branched noncanonical arylalanines. Our mechanistic investigation demonstrates that, upon transamination, the lysine-derived ketone byproduct readily cyclizes to a six-membered imine, driving the equilibrium in the desired direction and thus alleviating the need to load superstoichiometric quantities of the amine donor or deploy a multienzyme cascade. Lysine also shows good overall compatibility with a panel of wild-type transaminases, a promising hint of its application as a smart donor more broadly. Indeed, by this approach, we furnished a broad scope of ß-branched arylalanines, including some bearing hitherto intractable cyclopropyl and isopropyl substituents, with high yields and excellent selectivities.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Aminas / Aminoácidos / Transaminases / Lisina Idioma: En Revista: J Am Chem Soc Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Aminas / Aminoácidos / Transaminases / Lisina Idioma: En Revista: J Am Chem Soc Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos