Total Synthesis and Adjuvant Activity of All Stereoisomers of Pinellic Acid

Abstract—Pinellic acid is a novel and potentially useful oral adjuvant when used in conjunction with intranasal inoculation of influenza HA vaccines. All stereoisomers of pinellic acid have been synthesized via regioselective asymmetric dihydroxylation, regioselective inversion, and stereoselective reduction, and their adjuvant activities were characterized. Among this series of iso-mers, 9S, 12S, 13S compound has the most potent adjuvant activity. Structure–activity relationships are discussed. # 2003 Elsevier Science Ltd. All rights reserved. Influenza is a highly infectious acute respiratory disease caused by specific influenza viruses leading to both worldwide pandemics and local outbreaks. Influenza virus infection is sometimes critical for patients with respiratory diseases such as bronchial asthma, immunosuppressive syndrome such as AIDS, or for aged persons with cardiopulmonary disease.1 Influenza vaccine is useful as prophylaxis of influenza virus infection.1 Intranasal inoculation of influenza vaccine has been tried to increase its safety and to pre