Total Synthesis of (–)-Jiadifenolide
An Eight-Step Gram-Scale Synthesis of (–)-Jiadifenolide.
Nat. Chem. 2015;
18 August 2015 (online)
Jiadifenolide is one of a number of secondary metabolites with neurotrophic activity isolated from the Illicium genus. The authors present a short route towards this natural product relying on a diastereoselective coupling of two butenolides. The strategy might allow for the synthesis of structurally related neurotrophic natural products.
Chiral bicycle D was prepared from (+)-citronellal via a short dehydration–ozonolysis–hetero-Pauson–Khand sequence. The lithium dienolate derived from D was diastereoselectively coupled with building block F to give the entire carbon skeleton G upon treatment with excess LDA and Ti(Oi-Pr)4. Four more steps allowed the isolation of considerable amounts of jiadifenolide.