Lu H.-H, Martinez MD, Shenvi RA * The Scripps Research Institute, La Jolla, USA
An Eight-Step Gram-Scale Synthesis of (–)-Jiadifenolide.
Nat. Chem. 2015;
7: 604-607
Key words
(–)-jiadifenolide - stereoselective coupling - neurotrophic terpenes
Significance
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.
Comment
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.
