Photochemical <i>Е/Z</i> isomerization of isonicotinoyl hydrazones based on pyridoxine derivatives

Abstract

Isonicotinoyl hydrazone of 6-carbaldehyde pyridoxine 1, existing as a mixture of E and Z isomers, is known to exhibit potent activity against drug-resistant strains of M. tuberculosis. This article continues earlier research on the development of anti-tuberculosis drugs by examining the photostability of compound 1 and its structural analogs, which is important for the production of pharmaceutical substances and the determination of the specific activity of various isomers in vivo. Under the action of UV irradiation, a significant tarring of the reaction mixture in the solutions of compounds 1 and 2 containing free hydroxymethyl groups at positions 4 and 5 of pyridoxine was observed, apparently due to the formation of reactive ortho-quinone methides. However, when ketal protection was employed for hydroxymethyl groups in the pyridoxine derivative containing the isonicotinoyl hydrazone fragment at position 6, a transition from the thermodynamically more stable E isomer to Z isomer was induced by UV irradiation through the formation of an intramolecular hydrogen bond of the NH...Npyr type. In contrast, owing to the presence of an intramolecular hydrogen bond of the OH...NC=N type, the pyridoxine derivative bearing the isonicotinoyl hydrazone fragment at position 2, underwent no significant photoisomerization.

Keywords

• pyridoxine
• isonicotinoyl hydrazones
• photoisomerization