SYNTHETIC STUDY OF ALPHA-PYRONE MEROTERPE NOIDS, PYRIPYROPENES

The first total synthesis of the microbial alpha-pyrone meroterpenoid, (+)-pyripyropene A(1), acyl-CoA:cholesterol acyltransferase (ACAT) in hibitor, which is effective and concise convergent approach (14 steps, 9.3% overall yield), designed to afford easy access to both the natur al products and a variety of analogs, has been achieved. The key step is the coupling reaction between alpha-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 synth esized started from (+)-Wieland-Miescher ketons via stereoselective re ductive formylation, palladium associated carbonylation, and allylic o xidation. (+)-Pyripyropene E (36) also has been synthesized from farne syl acetate (9 steps, 9.6% overall yield). The convergent and stereose lective route exploited a biomimetic polyene cyclization as the key tr ansformation.