Four-Step Total Synthesis of (+)-Yaoshanenolides A and B

Abstract

A highly concise bioinspired four-step total synthesis of yaoshanenolides A and B possessing tricyclic spirolactone with an unusual 5′ H -spiro-[bicyclo[2.2.2]-oct[2]ene-7,2′-furan]-5′-one scaffold is reported. This synthesis features high-yielding aldol-type addition of γ-butyrolactone on to the aldehyde, exocyclic olefination of lactone derivative using Eschenmoser’s salt, and highly facial- and endo-selective [4 + 2]-cycloaddition of fully functionalized 5-methylene-2(5 H )-furanone with natural R -(−)-α-phellandrene. The approach allows access to yaoshanenolides A and B in four linear steps in 11 and 13% overall yield.