Total syntheses of natural (+)-(4R,6R)-4-hydroxy-6-pentylvalerolactone and of (–)-(6R)-massoialactone

An asymmetric total synthesis and hence a confirmation of the absolute configuration of naturally occurring (+)-(4R,6R)-4-hydroxy-6-pentylvalerolactone 10, a metabolite of Cephalosporium recifei, is described, starting from the yeast reduction product methyl (3R)-3-hydroxyhex-5-enoate 5. The key step is a highly trans-selective kinetic iodolactonization of the unsaturated acid 16e. Dehydration of the lactone 10 leads to natural (–)-(6R)-massoialactone 11.