Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• the activity is controlled by the ring C. Keywords: chiral resolution; configurational analysis; glutamate; metathesis; neuroactivity; Introduction The ionotropic glutamate receptor (iGluR) mediates the majority of the excitatory neurotransmission in the mammalian central nervous system (CNS) and

• Figure 1) [3][4], we found that 1) the (2R)-enantiomer is responsible for the neuroactivity and that 2) the activity is controlled by the structure of the ring C; the seven-membered azacyclic analog (2R)-TKM-107 (2) is moderately hypoactive, that is, it attenuates the voluntary movement of mice upon

• both enantiomers of MC-27, 4 and 4*, separately (see Figure 1 for the (2R)-enantiomer) and found that, as expected, the (2R)-enantiomer 4 is responsible for the neuroactivity (see above). Herein, we also report the enantiospecific synthesis and evaluation of the novel eight-membered azacyclic analog