Total Synthesis, Configuration Assignment, and Cytotoxic Activity Evaluation of Protulactone A

The first total synthesis and absolute configuration assignment of protulactone A (1) has been achieved. Four stereoisomers, 1a, ent-1a, 1b, and ent-1b, of this natural polyketide were prepared by chiral pool synthesis starting from and D-arabinose, respectively. The absolute and relative configurations of all isomers were assigned by single-crystal X-ray analysis. Target compounds were screened for their in vitro cytotoxicity toward certain human tumor cells (NCI60 cancer cell line panel).