Progress Toward the Cortistatin A Carbocyclic Core and the Development of the Catalytic Enantioselective Alkylation of 3-Helooxindoles

Citation

Ma, Sandy (2011) Progress Toward the Cortistatin A Carbocyclic Core and the Development of the Catalytic Enantioselective Alkylation of 3-Helooxindoles. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/ZF1G-Y610. https://resolver.caltech.edu/CaltechTHESIS:10122010-162444550

Abstract

Biologically active natural products often contain interesting and complex structural features and functionalities that make them attractive targets for synthetic chemists. As such, these natural products can serve as inspiration for the development of new reaction methodology.

Cortistatin A contains a unique rearranged steroidal core and possesses potent anti-angiogenic activity. These features have made cortistatin A the target of many synthetic efforts, including ours. The progress toward the synthesis of the cortistatin A carbocyclic core via an enyne-ene metathesis is discussed. Our studies towards the construction of the cortistatin A carbocyclic core yielded an interesting result, wherein an attempted S_N2 inversion of a secondary mesylate afforded product with retention of stereochemistry.

Oxindole derived motifs are also prevalent in biologically active molecules. More specifically, 3,3-disubstituted oxindoles can be used to access pyrrolidinylspirooxindole and pyrrolidinoindoline cores. Herein, the development of a catalytic enantioselective malonate alkylation of 3-halooxindoles to access enantiopure 3,3-disubstituted oxindoles is detailed. We then demonstrate that the enantiopure 3,3-disubstituted oxindoles derived from this novel transformation can be used towards the construction of pyrrolidinylspirooxindole and pyrrolidinoindoline cores.

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