I. Completion of a Total Synthesis of Peloruside A II. Studies Toward the Total Synthesis of Spiro-prorocentrimine

I. Completion of a Total Synthesis of Peloruside A The completion of a 22 step synthesis of the marine natural product peloruside A is presented. The second generation strategy cuts 10 steps from longest linear sequence of the Evans group's first generation synthesis of peloruside A by changing the order of fragment coupling operations and maintaining C 1 and C9 at their final oxidation states over the course of most of the synthesis. Key steps include two highly diastereoselective aldol fragment couplings, a tin tetrachloride mediated hydrosilylation and a macrolactonization on a seco acid containing no cyclic templating elements.;II. Studies Toward the Total Synthesis of Spiro-prorocentrimine The development of an intermolecular Diels-Alder approach toward the marine natural product spiro-prorocentrimine is described. This work began with the adaptation of the Evans group's previous intramolecular Diels-Alder approach. It was found that protonated imines bearing non-coordinating counterions were of sufficient reactivity to allow cycloaddition to occur even on dienes that were unreactive under the previous best conditions. In the course of these studies, isomerization of a macrocyclic diene during the course of a Diels-Alder reaction complicated the stereochemical outcome of the reaction. Reaction conditions to suppress the isomerization and obtain Diels-Alder adducts bearing the correct configuration at both C9 and C 33 were developed based on a qualitative consideration of the pKas of species present in the reaction. The intrinsic facial selectivity of several macrocyclic dienes was examined to help explain the course of the Diels-Alder reaction. Other key steps include an iron catalyzed olefin formation, the highly diastereoselective hydrogenation of a trisubstituted olefin in the presence of an enol ether, protecting group studies to suppress the contraction of a 15 membered lactone to a 6 membered lactone and studies of a protecting group strategy to allow installation of a sulfate. Lessons learned from this work and previous efforts are combined in a proposal for a bioinspired synthesis of spiro-prorocentrimine with a longest linear sequence of less than 30 steps. *Please refer to dissertation for diagrams.