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. (c) 2006 Elsevier Ltd. All rights reserved.