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Methods for Syntheses of N-methyl-DL-aspartic Acid Derivatives

M Boros, J Kökösi, J Vámos, I Kövesdi, B Noszál

Amino Acids. 2007 Nov;33(4):709-17.

PMID: 17334906

Abstract:

A novel practical method for the synthesis of N-methyl-DL-aspartic acid 1 (NMA) and new syntheses for N-methyl-aspartic acid derivatives are described. NMA 1, the natural amino acid was synthesized by Michael addition of methylamine to dimethyl fumarate 5. Fumaric or maleic acid mono-ester and -amide were regioselectively transformed into beta-substituted aspartic acid derivatives. In the cases of maleamic 11a or fumaramic esters 11b, the alpha-amide derivative 13 was formed, but hydrolysis of the product provided N-methyl-DL-asparagine 9 via base catalyzed ring closure to DL-alpha-methylamino-succinimide 4, followed by selective ring opening. Efficient methods were developed for the preparation of NMA-alpha-amide 13 from unprotected NMA via sulphinamide anhydride 15 and aspartic anhydride 3 intermediate products. NMA diamide 16 was prepared from NMA dimethyl ester 6 and methylamino-succinimide 4 by ammonolysis. Temperature-dependent side reactions of methylamino-succinimide 4 led to diazocinone 18, resulted from self-condensation of methylamino-succinimide via nucleophyl ring opening and the subsequent ring-transformation.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP68315355 DL-Aspartic acid-4-13C DL-Aspartic acid-4-13C 68315-35-5 Price
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