Syntheses of α-(R)- and α-(S)-lipoic acid from (S)-malic acid

(S)-Malic acid has been converted into α-(R)- and α-(S)-lipoic acid [(1a) and (1b), respectively]via(R)- and (S)-(2-phenylmethoxyethyl)oxirane [(2a) and (2b), respectively]. The (R)-oxirane (2a) was cleaved with but-3-enylmagnesium bromide (cuprate catalysis) to give (S)-1-(phenylmethoxy)oct-7-en-3-ol (4a). This was converted into methyl (S)-6,8-dihydroxyoctanoate (5a), the di-O-methanesulphonate (6a) of which was treated with sodium sulphide and sulphur in dimethylformamide to yield methyl α-(R)-lipoate (7a), that was saponified to α-(R)-lipoic acid (1a). The (S)-oxirane (2b) was similarly converted into α-(S)-lipoic acid (1b).