Synthesis of L-(+)-ergothioneine

Article abstract of DOI:10.1021/jo00125a014

The first synthesis of L-(+)-ergothioneine (1), a rare natural amino acid, is described. The key step is the direct transformation of the imidazole derivative 11 into imidazole-2-thione 12. This reaction consists of the cleavage and the re-formation of imidazole ring (ANRORC) with phenyl chlorothionoformate via a Bamberger-type intermediate. The conditions used are mild enough to preserve the asymmetric center at the 1a-carbon. The release of enantiomerically pure L-ergothioneine (1) from the ammonium derivative 15 was performed under acidic conditions to avoid the very easy racemization of the betaine function. An efficient and high-yield sypthesis of 2-mercapto-L-histidine (2) which uses the new imidazole-2-thione formation reaction is also described.