ENANTIOSELECTIVE SYNTHESIS OF R-(-)-LIGULARENOLIDE AND THE PROGESTERONE-RECEPTOR LIGAND R-(-)-PF1092C STARTING FROM S-(-CARVONE())

A new enantioselective synthesis of eremophilane sesquiterpenes was de veloped starting from S-(+)-carvone 3, using a conjugate addition-anne lation sequence. The synthesis of R(-)-ligularenolide 1 was accomplish ed in a staightforward manner with the annelation of the lactone as th e last step. For the synthesis of the progesterone receptor ligand R-( -)-PF1092C 2 a different strategy was followed in which first the lact one was annelated. The concommitant isomerization of the double bond o f the isopropenyl group into the conjugate position then offered an al ternative way to remove the side chain and simultanuously provide for an ideal functionality for the introduction of the cis beta-diol funct ion at the C2,C3 position. (C) 1998 Elsevier Science Ltd. All rights r eserved.