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Please use this identifier to cite or link to this item: http://arks.princeton.edu/ark:/88435/dsp019880vv293
Title: STEREOSELECTIVE RADICAL CYCLIZATIONS CATALYZED BY ‘ENE’- REDUCTASES & SYNTHETIC STUDY TOWARD CURVULAROL
Authors: Gao, Xin
Advisors: SorensenHyster, ErikTodd
Contributors: Chemistry Department
Keywords: "Ene"-reductases
Biocatalysis
Photoenzymatic
Radical
Subjects: Chemistry
Issue Date: 2023
Publisher: Princeton, NJ : Princeton University
Abstract: Enzymes have a broad range of applications in chemical industrial processes because they are efficient catalysts that catalyze their natural reactions with exceptional levels of regio- and stereoselectivity. However, to date, enzymes’ non-natural reactivities have been rarely explored. It is therefore necessary to expand the reaction scope of enzymes, allowing chemists to take advantage of enzymes’ selectiveness while accessing more useful transformations. To expand the promiscuity of enzymes, my research focused on exploring novel reactivities of enzymes by exposing them to non-natural reaction conditions and then protein engineering to improve the non-natural reactivity.Chapter 2 describes a novel photoenzymatic radical C–C bond formation. The cofactor flavin and the substrate molecule α-chloroamide form a charge transfer complex in the enzyme active site. Upon visible light irradiation of the complex, a single electron is transferred from the reduced flavin to the substrate, generating the carbon-centered radical. This method enables syntheses of 5,6,7,8-membered lactams bearing β-chiral centers. Inspired by this new reactivity of flavoproteins to generate radicals, we utilized this method to prepare lactams with chiral α-tertiary amines. Chapter 3 explains the process of protein engineering of flavoproteins to improve reaction yields and stereoselectivities of products. Besides biocatalysis, the second theme of my graduate research is natural product synthesis. I worked on designing synthetic routes and conducting experiments to construct a novel trichothecene sesquiterpene curvularol. Recognized as an inhibitor for the mammalian cell cycle, curvularol has promising applications in oncology. Chapter 4 details various synthetic strategies to synthesize the key intermediate allyl vinyl ether that can undergo a Claisen rearrangement, yielding the product that bears vicinal quaternary centers.
URI: http://arks.princeton.edu/ark:/88435/dsp019880vv293
Type of Material: Academic dissertations (Ph.D.)
Language: en
Appears in Collections:Chemistry

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