Synthesis of valproic acid derivatives using pyridoxine as pro-moiety

Abstract

This investigation was to study the synthetic route of six valproic acid derivatives using pyridoxine as pro-moiety which were expected to possess anticonvulsant activity. The six-membered ring cyclic acetal of pyridoxine, 5-hydroxymethyl-8-methyl-2-(1-propylbutyl)-4H-dioxino[4,5-c] pyridine was obtained in quantitative yield by saturating the hydrogen chloride on 2-propylpentanal suspension of pyridoxine hydrochloride. The valproate esters of pyridoxine that are pyridoxine-5-valproate, pyridoxine-3-valproate, pyridoxine-3,5-divalproate, pyridoxine-3,4-divalproate, and pyridoxine trivalproate were prepared by selective esterification of pyridoxine using valproyl chloride as acylating agent. An attempt to synthesize the seven-membered ring cyclic acetal of pyridoxine, 9-hydroxy-8-methyl-3-(1-propylbutyl)-4H,9H-dioxepino[5,6-c]pyridine from the Diels-Alder reaction of 4-methyl-5-ethoxyoxazole and 2-(1-propylbutyl)-1,3-dioxep-5-ene was unsuccessful at temperature ranging from 180 ℃ for 48 hours to room temperature for 240 hours. The structures of the synthesized compounds were confirmed by infrared spectrometry, proton-1 and carbon-13 nuclear magnetic resonance spectrometry, and mass spectrometry techniques.