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Development of Oxidation and Transition Metal-Mediated Reactions and Application to Natural Product Synthesis

Citation

Dibrell, Sara Elise (2023) Development of Oxidation and Transition Metal-Mediated Reactions and Application to Natural Product Synthesis. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/ve4j-tw63. https://resolver.caltech.edu/CaltechTHESIS:04282023-211208336

Abstract

Expedient access to complex molecules via chemical synthesis is important for assessing their biological activity and medicinal properties. In one approach, convergent joining of fragments of similar size and complexity is followed by minimal scaffold tailoring steps to rapidly access natural products. This strategy hinges on the ability to (1) tailor peripheral oxidation, ideally via creative redox transformations, and (2) forge strategic bonds within a complex scaffold through C–C bond formation. We disclose efforts to address these aims by developing broadly useful chemical tools and applying them to the preparation of bioactive natural products.

Toward the first aim, we investigated unusual oxidative reactivity mediated by selenium dioxide. To address the second aim, we developed nickel-catalyzed reductive cross-coupling reactions to study: catalyst-controlled enantioselectivity in the preparation of medicinally relevant small molecules, substrate-controlled stereoselectivity, and selectivity for ring formation. The latter studies enabled the exploration of transition metal-mediated cyclization as a convergent annulation strategy toward the rearranged isoryanodane diterpene (+)-cassiabudanol A, as well as the formal synthesis of the macrocyclic cytotoxin (–)-cylindrocyclophane F.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Organic synthesis; natural products; transition metal catalysis
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Restricted to Caltech community only
Research Advisor(s):
  • Reisman, Sarah E.
Thesis Committee:
  • Robb, Maxwell J. (chair)
  • Stoltz, Brian M.
  • Peters, Jonas C.
  • Reisman, Sarah E.
Defense Date:1 March 2023
Funders:
Funding AgencyGrant Number
NSF Graduate Research FellowshipDGE-1144469
NIHR35GM118191
NSFCHE1800536
Bristol Myers SquibbUNSPECIFIED
Record Number:CaltechTHESIS:04282023-211208336
Persistent URL:https://resolver.caltech.edu/CaltechTHESIS:04282023-211208336
DOI:10.7907/ve4j-tw63
Related URLs:
URLURL TypeDescription
http://doi.org/10.1021/acs.accounts.0c00858DOIReview adapted for chapter 1
http://doi.org/10.1021/acscatal.0c01842DOIPerspective adapted for chapter 2
http://doi.org/10.1021/jacs.9b13818DOICommunication adapted for chapter 3
ORCID:
AuthorORCID
Dibrell, Sara Elise0000-0003-0332-1101
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:15148
Collection:CaltechTHESIS
Deposited By: Sara Dibrell
Deposited On:16 May 2023 16:16
Last Modified:08 May 2024 17:38

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