Suberosanes as Potential Antitumor Agents: First Enantioselective Total Synthesis of (1S)-Suberosanone and Configurational Assignment of Suberosenol A

Abstract

The first enantioselective total syntheses of two marine sesquiterpenes, natural (1<i>S</i>)-suberosanone and (1<i>S</i>)-suberosenol A, are achieved leading to the assignment of the absolute configuration of natural suberosenol A. A new access to (1<i>S</i>)-suberosenone from a key tricyclic enone was also developed leading to an overall improvement of the synthesis, allowing an efficient route to suberosenol A. Hyperbaric asymmetric Michael addition and a highly efficient silver trifluoroacetate mediated α-alkylation for the formation of ring A completed the key steps of the synthesis. Regrettably, synthetic (1<i>S</i>)-suberosanone did not retain the reported picomolar cytotoxic activity displayed by the natural product, the reason for which remains to be elucidated.