?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F35060%2F&rft.title=Synthesis+of+Small+Molecule+Antagonists+at+the+Androgen+Receptor+for+Prostate+Cancer+Treatment+and+Efforts+Toward+an+Enantioselective+Co(II)-Catalyzed+Cyclopropanation&rft.creator=Tai%2C+Serene&rft.description=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%5B1.1.0%5Dpentane+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%2C+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%25+ee+over+three+high-yielding+steps.&rft.date=2018-09-26&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F35060%2F1%2FSerene%2520Tai_MS%2520Thesis_08072018_1.pdf&rft.identifier=++Tai%2C+Serene++(2018)+Synthesis+of+Small+Molecule+Antagonists+at+the+Androgen+Receptor+for+Prostate+Cancer+Treatment+and+Efforts+Toward+an+Enantioselective+Co(II)-Catalyzed+Cyclopropanation.++Master's+Thesis%2C+University+of+Pittsburgh.++++(Unpublished)++