STUDIES ON THE OXIDATION PRODUCTS OF LIPOIC ACID

Abstract

1. When α-lipoic acid in chloroform was oxidized with 5 molar ratio of t-butyl hydroperoxide for 1 day at 40°, an unidentified lipoic acid derivative was detected at Rf 0.90 on the paper chromatogram using 2.8% aq. ammonia-saturated n-butanol as a developing agent. The substance was obtained as a yellow oil in about 5% yield. It was positive to KCN-nitroprusside reagent and exerted an inhibitory effect on Streptococcus faecalis 10 C1.The infrared spectrum indicates that the compound is t-butyl ester of lipoic acid sulfone. The free acid form (X) was obtained by hydrolysis in ca. 4% yield. The infrared spectrum of X was essentially identical with that of α-lipoic acid except that the peaks assignable to a sulfoxide group were observed at 1, 310cm-1 (νas SO2) and 1140cm-1 (νas SO2). Its elementary analysis value corresponded to that of monosulfone. X showed an inhibitory effect on Streptococcus faecalis 10 C1 with a 50% inhibition index of about 100.2. DL-α-Lipoic acid was oxidized with 2 molar ratio of hydrogen peroxide in aqueous acetone for 1 day at room temperature. An unidentified lipoic acid-active product was produced in addition to β-lipoic acid and unreacted α-lipoic acid in about 1% yield. It showed almost the same microbiological activity and elementary analysis value as those of β-lipoic acid. However, the characteristic peaks in the infrared as well as ultraviolet spectra showed some differences. The oxidation product is supposed to be an isomer of β-lipoic acid whose positon of a sulfoxide group is different, or a conformer based on a different steric positions of a sulfoxide group and a valeric acid side-chain attached to 1, 2-dithiolane ring. ORD studies on the oxidation product from an optically active lipoic acid is now in progress.3. Oxidation of α-lipoic acid with 10 molar ratio of hydrogen peroxide in glacial acetic acid resulted in the formation of a white precipitate (mp 108-110°). In the infrared spectrum, characteristic peaks due to a sulfoxide group were clearly observed. Its elementary analysis value was consistent with C8H14O6S2. The product was assumed to be a disulfone derivative of lipoic acid.