Synthesis of New C-3 Substituted Kynurenic Acid Derivatives

Bálint Lőrinczi; Antal Csámpai; Ferenc Fülöp; István Szatmári

doi:10.3390/molecules25040937

Synthesis of New C-3 Substituted Kynurenic Acid Derivatives

Molecules. 2020 Feb 19;25(4):937. doi: 10.3390/molecules25040937.

Authors

Bálint Lőrinczi^{1

2}, Antal Csámpai³, Ferenc Fülöp^{1

2}, István Szatmári^{1

2}

Affiliations

¹ Institute of Pharmaceutical Chemistry and Research Group for Stereochemistry, Hungarian Academy of Sciences, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
² Institute of Pharmaceutical Chemistry, University of Szeged, Interdisciplinary Excellence Center, Eötvös u. 6, H-6720 Szeged, Hungary.
³ Department of Inorganic Chemistry, Eötvös Loránd University (ELTE), Pázmány P. sétány 1/A, H-1117 Budapest, Hungary.

Abstract

The application of kynurenic acid (KYNA) as an electron-rich aromatic system in the modified Mannich reaction has been examined. The extension possibility of the reaction was tested by using amines occurring in a number of bioactive products, such as morpholine, piperidine, or N-methylpiperazine and aldehydes of markedly different reactivities, like formaldehyde and benzaldehyde. The influence of substituents attached to position 3 on the aminoalkylation was also investigated. Thus, reactions of 3-carbamoyl-substituted precursors with tertiary amine containing side-chains were also tested to afford new KYNA derivatives with two potential cationic centers. By means of NMR spectroscopic measurements, supported by DFT calculations, the dominant tautomer form of KYNA derivatives was also determined.

Keywords: DFT calculations; Mannich reaction; kynurenic acid; neuroprotective activity.

MeSH terms

Kynurenic Acid / analogs & derivatives*
Kynurenic Acid / chemical synthesis*
Kynurenic Acid / chemistry*

Substances

Kynurenic Acid