Convenient One-Pot Synthesis of Kynurenic Acid Ethyl Ester and Exploration to Direct Synthesis of Neuroprotective Kynurenic Acid and Amide Derivatives.
J Org Chem
; 88(15): 10494-10500, 2023 08 04.
Article
em En
| MEDLINE
| ID: mdl-37463064
ABSTRACT
Kynurenic acid (KYNA) is an endogenous molecule, which is a non-selective antagonist of ionotropic glutamate receptors and has been found to have neuroprotective activity. A supplement of KYNA may be applicable for the treatment of neurodegenerative disease, but it does not cross the blood-brain barrier due to its polar nature. Therefore, its different esters and amide derivatives were explored as a prodrug, which can cross blood-brain barrier and transform into KYNA in situ. However, many esters and amide derivatives of KYNA are synthesized via coupling reaction or multi-step synthesis using different organic or metallic catalysts. Herein, we developed a novel one-pot, catalyst-free, convenient synthesis of KYNA ethyl esters using aniline and diethyl acetylene dicarboxylate in DMF under heating. We also explored the synthesis of KYNA and KYNA amide derivative in a simple manner with overall good yields via hydrolysis and condensation, respectively.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Neurodegenerativas
/
Ácido Cinurênico
Limite:
Humans
Idioma:
En
Revista:
J Org Chem
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Índia