Unified Total Syntheses of Anticancer Agent Nepetaefolin F and Indolosesquiterpenoids, Oridamycins A and B

The asymmetric total syntheses of triptobenzene L (1a), 4-epi-triptobenzene L (1c), nepetaefolin F (1b), and oridamycins A (2c) and B methyl ester (2a) have been accomplished through an enantioselective divergent approach from a highly functionalized common intermediate. A Lewis-acid-mediated highly regio- and diastereoselective epoxy-ene cyclization of (−)-6 [92% ee] afforded the highly functionalized carbotricyclic core (+)-5 [82%, dr >20:1] sharing four contiguous stereogenic centers [out of which two are all-carbon quaternary stereogenic centers]. Efficient functionalization of the advanced intermediate enabled the successful asymmetric total syntheses of naturally occurring anti-cancer abietane diterpenoid, such as 1b and indolosesquiterpenoids 2a and 2c.