Solvolysis of enantioenriched dihalides and its application to the synthesis of the brominated chamigrene sesquiterpenes

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To date, more than 2,000 natural products have been isolated and structurally characterized which contain either a chlorine- or bromine-bearing stereocenter. Of these secondary metabolites, approximately 500 contain a brominated five-, six-, or seven-membered cyclic scaffold that is often further embedded within a larger terpene-derived polycyclic architecture. Despite the abundance of these motifs in nature, synthetic technologies providing enantioselective access to these structures are largely deficient. To access such structural motifs, we developed a methodology wherein enantioenriched bromochlorides were subjected to ionizing media (hexafluoroisopropanol) to generate a non-racemizing bromonium ion, which could be captured intramolecularly leading to a cyclized product with near-perfect enantiospecificity. This solvolytic bromonium-initiated cyclization was used to access numerous natural product-relevant scaffolds. The analogous enantioenriched dibromides were found to rapidly racemize under these ionizing conditions. This methodology was applied to the synthesis of several brominated chamigrene sesquiterpenes, a class of approximately 100 red algal-derived secondary metabolites. The flagship member of this class, (+)-aplydactone, and its putative biosynthetic precursor, (--)-dactylone, were synthesized enantioselectively for the first time.


Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource.
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2018; ©2018
Publication date 2018; 2018
Issuance monographic
Language English


Author Burckle, Alexander James
Degree supervisor Burns, Noah
Thesis advisor Burns, Noah
Thesis advisor Du Bois, Justin
Thesis advisor Waymouth, Robert M
Degree committee member Du Bois, Justin
Degree committee member Waymouth, Robert M
Associated with Stanford University, Department of Chemistry.


Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Alexander James Burckle.
Note Submitted to the Department of Chemistry.
Thesis Thesis Ph.D. Stanford University 2018.
Location electronic resource

Access conditions

© 2018 by Alexander James Burckle
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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