Synthesis of 9-Substituted Carbacyclin Analogues

Article abstract of DOI:10.1021/jo00174a035

The synthesis of a series of 9-substituted carbacyclin analogues with potent platelet antiaggregatory activity is described.The key step for the formation of 9-acetylene compounds (e. g., 8d) utilized a modification of the Schwartz procedure involving the nickel-catalyzed conjugate addition of the appropriate alkynyl aluminate to bicyclo<3.3.0>oct-1-en-3-one (2).It was found that 9-methylcarbacyclin (8b) could be prepared by a similar procedure.In addition, a novel alternative to the Wittig reaction for introducing the carbacyclin upper side chain in base-sensitive substrates was developed which involves the addition of the dianion of 6-((tert-butyldimethylsilyl)oxy)hexanoic acid to the appropriate ketone (e. g., 6f or 2) followed by decarboxylative dehydration of the resulting β-hydroxy acid.