[摘要]：A total synthesis of largazole was achieved. The optically active b-hydroxycarbonyl unit was prepd. from modified Nagao's N-acetylthiazolidinethione. A 4-methylthiazoline-thiazole amino ester was prepd. by both a step-by-step method and tandem cyclization from Cys-2-MeCys-contg. tripeptide. Amidation of the activated b-hydroxycarbonyl unit and the 4-methylthiazoline-thiazole-contg. amino ester, followed by esterification with N-Fmoc-valine afforded a cyclization precursor after selective removal of the C-terminal Me ester and the N-terminal Fmoc group. Macrolactamization, deprotection of the thiol, and S-acylation provided largazole. S-modified derivs. as well as synthetic largazole itself exhibited strong inhibitory activity against histone deacetylases (HDAC).
