Lipase-catalyzed kinetic resolution of tetronic acid derivatives bearing a chiral quaternary carbon: total synthesis of (S)-(−)-vertinolide

We have developed a chemoenzymatic synthesis of (S)-vertinolide 1 with a chiral quaternary carbon atom at C5. In the kinetic resolution of tetronic acid precursor 6, lipase PS-D furnished the recovered alcohol 6 with an (R)-stereochemistry in a ratio of 95% ee, whereas lipase AY gave (S)-alcohol 6 with 93% ee. Chemical transformations of (S)-alcohol 6 provided (S)-vertinolide 1 in 33% yield in five steps with no loss of enantiomeric excess.

Graphical abstractBoth enantiomers were obtained with high enantiomeric excess by lipase-catalyzed kinetic resolution of tetronic acid derivatives. Total synthesis of (S)-vertinolide from (S)-alcohol was achieved in 33% yield in five steps.Figure optionsDownload full-size imageDownload as PowerPoint slide

(S)-4-Hydroxy-3,5-dimethyl-5-((4E,6E)-3-oxoocta-4,6-dienyl)furan-2(5H)-oneC14H18O4Ee = 94%[α]D26=-25.8 (c 0.05, CHCl3)