%0 Generic
%9 Master's Thesis
%A Tai, Serene
%D 2018
%F pittir:35060
%K Prostate cancer treatment, androgen receptor,  cyclopropanation, fluorination, enantioselective cis-cyclopropanation, metabolic stability
%T Synthesis of Small Molecule Antagonists at the Androgen Receptor for Prostate Cancer Treatment and Efforts Toward an Enantioselective Co(II)-Catalyzed Cyclopropanation
%U http://d-scholarship-dev.library.pitt.edu/35060/
%X This thesis describes the synthesis of fluorinated cyclopropane analogues to enhance the metabolic stability of a previously published lead candidate for prostate cancer treatment. A structural unique motif such as the bicyclo[1.1.0]pentane was also incorporated to investigate its potential as cyclopropane bioisostere. Preliminary results from liver microsome and luciferase assays suggested that fluorinations on the cyclopropane carbon atoms have little impact on the metabolic stability. However, fluorination on other labile sites showed enhanced metabolic stability while retaining compound potency. An enantioselective route to improve the original racemic synthesis of these analogues was also investigated. The key step was a Co(II)-salen catalyzed enantioselective cis-cyclopropanation of an olefin with ethyl diazoacetate to provide the cyclopropyl amide in 98% ee over three high-yielding steps.