Synthesis of amide derivatives of valproic acid การสังเคราะห์อนุพันธ์เอไมด์ของวัลโปรอิกแอซิด

Abstract

This investigation was to study the synthetic route of amide derivatives ofvalproic acid, which were expected to possess anticonvulsant activity. The formation of N{2-propylpentanoyl)-L-proline proceeded by reacting2-propylpentanoyl chloride with amino acid in 10% sodium hydroxide solution. Thesynthetic route of N{2-propylpentanoyl)-L-proline ethyl ester,N{2-propylpentanoyl)-DL-serine methyl ester, N{2-propylpentanoyl)-DL-serine ethylester, and N{2propylpentanoyl)-glycine ethyl ester involved esterification of theamino acid with the corresponding alcohol in the presence of thionyl chloride, thenfollowed by the acylation with 2-propylpentanoyl chloride in the presence oftriethylamine. The synthetic route of N-(2-propylpentanoyl>L-proline benzylamide,N(2-propylpentanoyl)-DLserine benzylamide, and N(2-propylpentanoyl)-glycine benzyla,mide involved coupling of the N(2propylpentanoy0-amino acid with benzylamine in thepresence of N,N -dicyclohexylcarbodiimide. The synthetic route ofN(2-propylpentanoyl)-DL-serine involved basic hydrolysis ofN(2-propylpentanoyl)-DL-serine methyl ester. The synthetic route of N-hydroxymethyl-2-propylpentamide involved amidation of2-propylpentanoyl chloride by concentrated ammonia solution to yield2-propylpentamide, followed by the reaction with 37% formaldehyde in the presence ofpotassium carbonate. The synthesis of N-acetoxymethyl-2-propylpentamide involvedacetylation of N-hydroxymethyl-2-propylpentamide with acetic anhydride. The syntheticroute of N-methoxymethyl-2-propylpentamide involved N-alkylation ofN-2-propylpentamide with methoxymethyl chloride using sodium hydride as a base. The structures of the synthesized compounds were confirmed by infraredspectrometry, proton-1, and carbon-13 nuclear magnetic resonance spectrometry, massspectrometry, and elemental analysis techniques.