Conversion of (+)-Limonen-10-ol to Bicyclo[3.3.0]octane Skeleton. Synthesis of a Key Intermediate for Carbacyclin

Abstract

The conversion of (+)-limonen-10-ol (7) into the key intermediate for the synthesis of carbacyclin (1), (+)-(1S, 2R, 3R, 5R)-3-acetoxy-2-methoxycarbonyl-7-oxobicyclo[3.3.0]octane (2), is described. The cis-3, 4-disubstituted cyclopentanone prepared from 7 via a sequence of reactions involving Rh(I)-catalyzed cyclization could be converted to the 3-acetylbicyclo[3.3.0]oct-2-ene skeleton, which was subjected to 1, 4-addition reaction with CN-. The resulting cyano compound was transformed into the key intermediate 2 through appropriate modification of the substituents on the five-membered ring. This synthetic method provides a new route to carbacyclin. © 1987, The Pharmaceutical Society of Japan. All rights reserved.