Total synthesis of an anticancer norsesquiterpene alkaloid isolated from the fungus Flammulina velutipes

Abstract

The first total synthesis of a norsesquiterpene alkaloid (R)-8-hydroxy-4,7,7-trimethyl-7,8-dihydrocyclopenta[e]isoindole-1,3(2H,6H)-dione, isolated from the mushroom-forming fungus Flammulina velutipes, in both racemic and enantiomeric pure forms, is reported. The (−)-enantiomer of the natural product has been synthesized from the D-(−)-pantolactone chiral pool. The synthesis features a one-pot, three-step reaction sequence comprising an enyne RCM/Diels–Alder/aromatization to construct the desired indane skeleton present in the natural product. Our synthesis further confirms the assigned structure and absolute configuration of the natural product.