Catalytic Asymmetric Bond Constructions in Complex Molecule Synthesis. An Approach to the Synthesis of Spirolide C and the Development of Enantioselective Enolate Hydroxylation Reactions

摘要

The asymmetric synthesis of spirolide C, a highly potent marine toxin, has been investigated in our laboratory. The construction of C7-C28 bis-spiroketal was completed through a strategy utilizing an intermolecular Stetter reaction and a biomimetic ketalization process. Stereocenters were set in great diastereo- and enantioselectivity via asymmetric catalysis. The efficiency of the synthesis was demonstrated by its convergency and high yields. ududA cinchona alkaloid catalyzed ketene-oxaziridine cyclocondensation has been developed to provide an access to enantioenriched α-hydroxy carbonyl compounds. The oxazolidinones arising from the cyclocondensation were converted to various α-hydroxy carbonyl compounds via nucleophilic ring openings. Greater than 98% ee was achieved in oxazolidinone formation and the subsequent ring openings proceeded with retention of the ee or minor epimerization.ud