Collective Syntheses of Guaiane Sesquiterpenes: Stereoselective Syntheses of (+)-Dysodensiol F, (+)-10β,14-Dihydroxy-allo-aromadendrane, and (-)-Dendroside C Aglycon.

Abstract

A collective synthetic route for tricyclic guaiane sesquiterpenes and total syntheses of (+)-dysodensiol F, (+)-10β,14-dihydroxy-allo-aromadendrane, and (-)-dendroside C aglycon starting from a versatile hydroazulene intermediate were accomplished. The key features of these syntheses involve late-stage carbene-mediated diastereoselective cyclopropanation, construction of an unusual cis-fused-hydroazulene skeleton via intramolecular Dieckmann condensation, and highly stereoselective tandem conjugate addition/intramolecular allylic alkylation to afford a 5/7/3 tricyclic skeleton of guaiane natural products. The synthesis of (-)-dendroside C aglycon and the first total synthesis of (+)-dysodensiol F and (+)-10β,14-dihydroxy-allo-aromadendrane are described in detail. Activation of the Nrf2/ARE signaling pathway by (-)-dendroside C aglycon is also disclosed via our synthesis.