Lipoic acid → alpha Lipoic acid

Participants

Reaction Steps

The synthesis of lipoic acid chloride (DL-thioctic acid) was carried out under argon at ambient temperature following a standard protocol: lipoic acid (5 g, 24 mmol) is solubilised in dichloromethane (40 ml) and SOCl2 (1.3 eq) is added dropwise. After 1 hour of stirring at ambient temperature, the lipoic acid chloride formed is poured onto a solution of resveratrol diacetate (1.2) (6 g, 19 mmol) in THF (100 ml), containing triethylamine (3 eq) and DMAP (0.45 eq). After 1 hour the reaction mixture is diluted with 100 ml CH2Cl2, then washed with two times 90 ml of HCl 5% v/v. The organic phase is dried over anhydrous MgSO4, filtered, then concentrated in a rotary evaporator. The crude product (11.4 g) is purified by chromatography on a column of silica with cyclohexane/ethyl acetate (4/1 v/v) as eluent. The fractions containing the pure product are evaporated to lead to 5.95 g of 3,5-resveratrol diacetate-4′-lipoate 1 (49% of yield) with a molar purity measured by NMR of the proton of 96%.

Provenance & Evidence