Synthetic study of α-pyrone meroterpenoids, pyripyropens

Abstract

The first total synthesis of the microbial α-pyrone meroterpenoid, (+)-pyripyropene A(1), acyl-CoA : cholesterol acyltransferase (ACAT) inhibitor, which is effective and concise convergent approach (14 steps, 9.3% overall yield), designed to afford easy access to both the natural products and a variety of analogs, has been achieved. The key step is the coupling reaction between α-pyrone-pyridine moiety (4) and the acid chloride of sesquiterpene moiety (3) in the presence of Lewis acid to construct ketone (2). The sesquiterpene moiety has been synthesized started from (+)-Wieland-Miescher ketons via stereoselective reductive formylation, palladium associated carbonylation, and allylic oxidation. (+)-pyripyropene E (36) also has been synthesized from farnesyl acetate (9 steps, 9.6% overall yield). The convergent and stereoselective route exploited a biomimetic polyene cyclization as the key transformation.