I. Catalytic enantioselective decarboxylative thioester aldol reactions. II. Enantioselective synthesis of (+)-cortistatin A

The development of enantioselective aldol reactions utilizing malonic acid half thioesters (MAHTs) is described in this thesis. Propionate aldol reactions utilizing methyl malonic acid half thioester (MeMAHT) and Cu(II)/bis(oxazoline) complexes provided beta-hydroxythioesters with high yields and high stereoselectivities (>89% ee, >5:1 dr). The mild reaction conditions allowed aldehydes bearing various reactive functional groups to be used without decreasing the reactivities and stereoselectivities. A proposed reaction mechanism and a stereochemical model are discussed.;The total synthesis of (+)-cortistatin A is also described. Cortistatin A is a steroidal alkaloid isolated from the marine sponge Corticium simplex. Cortistatin A was reported to be a highly potent and selective anti-angiogenic agent. The key reaction in the synthesis is a tandem aza-Prins cyclization/transannular etherficiation, by which the A- ring and C5-oxobridge were built diastereoselectively. Hajos-Parrish ketone was used as the starting material, and the C8-tertiary carbinol was installed by diastereoselective Rubottom oxidation. The seven-membered B-ring was provided by silicate-directed ring expansion reaction. The synthesis was concluded by installing C17-isoquinoline by Stille coupling followed by diimide reduction of the C16-C17 alkene.