Enantioselective synthesis of R-(-)-ligularenolide and the progesterone receptor ligand R-(-)-PF1092C starting from S-(+)-carvone

A new enantioselective synthesis of eremophilane sesquiterpenes was developed starting from S-(+)-carvone 3, using a conjugate addition-annelation sequence. The synthesis of R(-)-ligularenolide 1 was accomplished in a staightforward manner with the annelation of the lactone as the last step. For the synthesis of the progesterone receptor ligand R-(-)-PF1092C 2 a different strategy was followed in which first the lactone was annelated. The concommitant isomerization of the double bond of the isopropenyl group into the conjugate position then offered an alternative way to remove the side chain and simultanuously provide for an ideal functionality for the introduction of the cis beta-diol function at the C2,C3 position. (C) 1998 Elsevier Science Ltd. All rights reserved.