Synthetic studies on the natural products Zoanthamine and Balanol

Abstract: Three main projects are described in this thesis. In the first, a stereocontrolled route tothe marine alkaloid Zoanthamine was studied. A convergent approach based on thechiral starting materials (S)-Perillyl alcohol and (R)-4,5-Dihydro-5-hydroxymethyl-2(3H)-furanone was developed. Some of the key reactions for control ofstereochemistry were: Sharpless asymmetric epoxidation, [3,3] sigmatropicrearrangement, iodolactonization-elimination, and diastereoselective alkylation.Intermediates corresponding to the C1-C5, C6-C10, and Cll-C24 fragments ofZoanthamine have been synthesized regio- and stereoselectively.In the second project, the total synthesis of (-) Balanol has been accomplished.Enantioselective synthesis of the hexahydroazepine ring involved introduction of thetwo stereogenic centres via Sharpless asymmetric epoxidation of an acyclic allylicalcohol, followed by acid-catalysed ring-opening of a bicyclic aziridine intermediate.The third project deals with a further study of the regio- and stereoselective ring-opening reaction discovered in the balanol project. The ring-opening of the three chiralbicyclic systems (one epoxide and two aziridines) was investigated, with a number ofdifferent nucleophiles and counter-ions. In most cases, excellent regio- andstereoselective was observed. The results from DNMR experiments, X-raycrystallography, and molecular mechanics calculations were used to provide anexplanation for the observed selectivity, which is postulated to originate from acombination of steric and electronic factors.