Synthesis of Acuminolide and 17-<i>O</i>-Acetylacuminolide from (+)-Sclareolide

Abstract

The synthesis of natural acuminolide and 17-O-acetylacuminolide is reported. Commerically available (+)-sclareolide was converted to epoxy alcohol 3, which upon acid-catalyzed cyclization afforded tricycle 14. Reaction of 14 with 1O2 in the presence of a hindered base gave an inseparable mixture of acuminolide 1a and 16-epiacuminolide 1b in a 70:30 ratio. Chromatographic separation of the diacetates of 1a and 1b afforded pure 18a and 18b. An analogous reaction sequence was used in the synthesis of 17-O-acetylacuminolide (2a) and 16-epi-17-O-acetylacuminolide (2b).