caa a22 4500 463186567 CHVBK 20180406164855.0 cr unu---uuuuu 170326e20071101xx s 000 0 eng 10.1007/s00726-006-0453-4 doi (NATIONALLICENCE)springer-10.1007/s00726-006-0453-4 Methods for syntheses of N -methyl- DL -aspartic acid derivatives [Elektronische Daten] [M. Boros, J. Kökösi, J. Vámos, I. Kövesdi, B. Noszál] Summary.: 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 α-amide derivative 13 was formed, but hydrolysis of the product provided N-methyl-DL-asparagine 9 via base catalyzed ring closure to DL-α-methylamino-succinimide 4, followed by selective ring opening. Efficient methods were developed for the preparation of NMA-α-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. Springer-Verlag, 2007 Keywords: N -methyl-aspartic acid - Regioselective ester and amide formation - Ring transformations - Methylamino succinimide - Diazocinone nationallicence Boros M. Department for Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary aut Kökösi J. Department for Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary aut Vámos J. Department for Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary aut Kövesdi I. EGIS Pharmaceuticals PLC, Budapest, Hungary aut Noszál B. Department for Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary aut Amino Acids Springer-Verlag 33/4(2007-11-01), 709-717 0939-4451 33:4<709 2007 33 726 https://doi.org/10.1007/s00726-006-0453-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00726-006-0453-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Boros M. Department for Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary aut NATIONALLICENCE 700 1- Kökösi J. Department for Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary aut NATIONALLICENCE 700 1- Vámos J. Department for Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary aut NATIONALLICENCE 700 1- Kövesdi I. EGIS Pharmaceuticals PLC, Budapest, Hungary aut NATIONALLICENCE 700 1- Noszál B. Department for Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary aut NATIONALLICENCE 773 0- Amino Acids Springer-Verlag 33/4(2007-11-01), 709-717 0939-4451 33:4<709 2007 33 726 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer