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Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
Published on: February 16, 2018
Access to Unnatural α-Amino Acids via Visible-Light-Mediated Decarboxylative Conjugate Addition to Dehydroalanine
Akshay A Shah1, Michael J Kelly1, James J Perkins1
1Department of Discovery Chemistry, Merck & Company, Inc., 770 Sumneytown Pike, West Point, Pennsylvania 19486, United States.
Abstract:
An expedient synthesis of β-alkyl α-amino acids is reported via application of decarboxylative photocatalysis. The method utilizes abundant, diverse, and inexpensive carboxylic acids to provide radicals for conjugate addition to dehydroalanine ester. High-throughput experimentation revealed an acridinium-based photocatalyst, tetraMeO-Acri-N-diMeOPh, to be the optimal choice enabling a general method that is tolerant to a wide range of functional groups. A scalable batch protocol and a parallel library synthesis for accessing diverse unnatural α-amino acids are described.
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