Spectroscopic Studies of 6-Membered Lipoic Acid Derivative, 1,2,3-Trithiane-4-pentanoic Acid, and Its Characteristic Stereochemical Profiles

Inserting a sulfur atom into the 1,2-dithiolane ring of lipoic acid (LA racemate) is a promising approach for improving the diversity of lipoic acid (LA racemate). For this purpose, we prepared 1,2,3-trisulfur-lipoic acid derivatives (trisulfur lipoic acid (<i>R</i>-enantiomer, TR-LA, trisulfur lipoamide, racemate TLPA)) by the reaction of R-LA (lipoic acid <i>R</i>-enantiomer) or lipoamide (LPA) and H₂S and performed precise stereochemical studies. As a result, the 6-membered-1,2,3-trisulfur ring (TR-LA and TLPA) showed a completely different profile from that of the five-membered dithiolane compounds (R-LA and LPA) in ¹H- and ¹³C-NMR spectroscopy. Raman spectroscopy of TR-LA and TLPA showed a different profile to that of LA and LPA, which also indicates the uniqueness of the 6-membered 1,2,3-trisulfur ring chromophore. The regeneration of lipoic acid from 1,2,3-trisulfur lipoic acid (TR-LA) was achieved using a phosphine derivative and sodium cyanide while maintaining the stereochemistry of the chirality center, with an almost quantitative yield.