Asymmetric total synthesis of humulane sesquiterpenoids alashanoids B, C, E, and F and 2,9-humuladien-6-ol-8-one

Abstract

Naturally occurring sesquiterpenes having humulane frameworks are structurally intriguing and possess significant biological profiles. Asymmetric synthesis of the alashanoids B, C, E, and F and 2,9-humuladien-6-ol-8-one is achieved for the first time through a linear synthetic strategy. Intramolecular late-stage Nozaki–Hiyama–Kishi (NHK) coupling is employed to access the eleven-membered macrocyclic core present in the target molecules. The NHK precursors are accessed using the Evans and non-Evans syn and anti-aldol reaction as a key transformation. X-ray and ECD analysis reconfirmed the synthesized compounds’ structures and chirotopical properties.