Concise Syntheses of (−)-11-O-Debenzoyltashironin and (−)-Bilobalide

Abstract

This account describes two concise total syntheses of complex sesquiterpenes, (−)-11-O-debenzoyltashironin and (−)-bilobalide as GABA_ARs antagonists, to investigate their biological effects and therapeutic potential. The synthesis of (−)-11-O-debenzoyltashironin in only six steps from butenolide heterodimer includes the ring-opening of a bridged lactone, the stereoselective α-oxidation of a congested amide, Mukaiyama hydration to form the trans-hydrindane skeleton, and an unusually facile trans-annular Dieckmann-type C-C bond formation. On the other hand, the synthesis of (−)-bilobalide, one of the secondary metabolites from Ginkgo Biloba, has been achieved in only twelve steps from the appropriate starting materials, which incorporated many oxidation states. This study has laid a foundation for new, enabling chemistry-an asymmetric Reformatsky reaction, a solvent-controlled Mukaiyama hydration, and a γ-lactonization of homopropargyl alcohol via intramolecular ketene trapping- and a platform for the functional modification of bilobalide.