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Updated: Nov 12, 2025

Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
Published on: February 16, 2018
Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs
Kenji Morokuma1, Shuntaro Tsukamoto1, Kyosuke Mori1
1Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama 236-0027, Japan.
Abstract:
Herein, we report the enantiospecific synthesis of two artificial glutamate analogs designed based on IKM-159, an antagonist selective to the AMPA-type ionotropic glutamate receptor. The synthesis features the chiral resolution of the carboxylic acid intermediate by the esterification with ʟ-menthol, followed by a configurational analysis by NMR, conformational calculation, and X-ray crystallography. A mice in vivo assay showed that (2R)-MC-27, with a six-membered oxacycle, is neuroactive, whereas the (2S)-counterpart is inactive. It was also found that TKM-38, with an eight-membered azacycle, is neuronally inactive, showing that the activity is controlled by the ring C.
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