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Nathan Jeffrey Line Dissertation Thesis Final.pdf (4.91 MB)
ETD Abstract Container
Abstract Header
Total Synthesis of Salvinorin A via an IMDA-Tsuji Allylation Strategy
Author Info
Line, Nathan
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=osu1461161309
Abstract Details
Year and Degree
2016, Doctor of Philosophy, Ohio State University, Chemistry.
Abstract
Salvia divinorum, a Mexican sage, was used for hundreds of years by the Mazatec Indians for both medicinal and religious purposes. These hallucinogenic properties have caused a recent interest in the recreational drug world and therefore, resulted in a multitude of laws/restrictions banning Salvia from the United States as well as many other countries around the world. In 1982, Ortega reported the first isolation of the neoclerodane diterpenoid, salvinorin A, from Salvia divinorum. Valdes later confirmed this finding independently two years later. It was determined that salvinorin A was the compound responsible for the hallucinogenic effects experienced through ingestion or inhalation of Salvia. Interestingly, salvinorin A was and has remained the only nonalkaloid hallucinogen as well as the first highly potent and selective ¿-opioid receptor agonist. These properties have not only piqued the interest of synthetic chemists but also medicinal chemists towards its potential role as a therapeutic agent. Herein is a summary of my total synthesis of salvinorin A with the goals to innovate a flexible and reliable total synthesis of salvinorin A and analogs to pursue SAR studies. I have developed an efficient synthesis of the decalin core that overcame obstacles and scale-up issues in the routes established by previous members. Utilizing the linear dithiane Diels-Alder precursor, I was able to implement an intramolecular Diels-Alders (IMDA)/Tsuji allylation combination to stereoselectively install the decalin core with both quaternary centers. Bistriflate formation followed by a palladium-mediated methoxy carbonylation provided the functional group handles needed to construct the skeletal framework. The furan moiety was installed selectively using a BINOL-titanium catalyst with a furyltitanim nucleophile. Conjugate reduction of both the methyl ester and furyl-lactone functional groups using SmI2 followed by diol manipulation provided targeted natural product salvinorin A.
Committee
Craig Forsyth, Prof. (Advisor)
Anita Mattson, Prof. (Committee Member)
David Nagib, Prof. (Committee Member)
Pages
192 p.
Subject Headings
Chemistry
;
Organic Chemistry
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Citations
Line, N. (2016).
Total Synthesis of Salvinorin A via an IMDA-Tsuji Allylation Strategy
[Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1461161309
APA Style (7th edition)
Line, Nathan.
Total Synthesis of Salvinorin A via an IMDA-Tsuji Allylation Strategy.
2016. Ohio State University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=osu1461161309.
MLA Style (8th edition)
Line, Nathan. "Total Synthesis of Salvinorin A via an IMDA-Tsuji Allylation Strategy." Doctoral dissertation, Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1461161309
Chicago Manual of Style (17th edition)
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Document number:
osu1461161309
Download Count:
1,544
Copyright Info
© 2016, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.