SYNTHESIS OF THE THIAZOLINE-BASED SIDEROPHORE (S)-DESFERRITHIOCIN

A total synthesis of the new thiazoline-based siderophore desferrithiocin 1, isolated from Streptomyces antibioticus, is described. Thus, a concise synthesis of (S)-2-methylcysteine hydrochloride 11 is first developed based on a modification of Seebach's ''self-reproduction of chirality'' protocol using the thiazolidine intermediate 8 derived from (S)-cysteine and pivaldehyde as a key intermediate. When a solution of (S)-2-methylcysteine hydrochloride is heated with 2-cyano-3-hydroxypyridine in the presence of triethylamine, (S)-desferrithiocin is produced in 97% yield. In a similar manner, use of (R)-2-methylcysteine in a cyclocondensation with 2-cyano-3-hydroxypyridine led to (R)-desferrithiocin, in a similar yield.