Liang Xi, Di Wu, Hong-You Zhu, Cong-Hai Zhang, Yi Jin and Jun Lin Pages 197 - 201 ( 5 )
N-Methyl-D-aspartic acid (NMDA) has significant potential as a drug to treat diabetes, Parkinson’s and Alzheimer’s disease. Consequently, many efforts have been made for synthesis of NMDA, but there exist some flaws yet. In this paper, we report an improved method for Large-Scale Synthesis of optically pure NMDA by Eschweiler–Clarke reaction and deprotection of benzyl by ACE-Cl reagent. The synthesis has been achieved in five steps with an overall yield of 70% and an enantiomeric excess over 99.5%, in particularly, the method avoided the use of toxic methylation reagent. This method can be scaled up to kilogram quantities, providing a solid basis for its further bioactivity studies and drug development.
Eschweiler–Clarke reaction, large-scale, Methylation, reductive amination.
Key Laboratory of Medicinal Chemistry for Natural Resource (Yunnan University), Ministry Education, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, P.R. China.