Convergent Synthesis of (−)-Mirabazole C Using a Chloroimidazolidium Coupling Reagent, CIP

Convergent synthesis of (−)-mirabazole C ( 1 ), a tetra thiazoline/thiazole alkaloid isolated from blue-green alga, has been described. The successive thiazoline rings of (−)-mirabazole C were formed by a single-step cyclization mediated by TiCl 4 treatment of tripeptide amide 4 . Convergent synthesis of the key intermediate 33 derived from three 2-methylcysteine residues was first achieved using a newly developed coupling reagent, 2-chloro-1,3-dimethylimidazolidium hexafluorophosphate (CIP). The effectiveness of CIP for the coupling of α,α-dialkyl amino acids and the reaction pathway of the activation were clarified by the syntheses of model peptides containing an α,α-dimethylamino acid. A practical method of asymmetric synthesis of 2-methylcysteine by alkylation of 2,4- cis -oxazolidinone 23 has also been described.