McCabe, Stephanie R
(2018)
ENANTIOSELECTIVE CYCLOPROPANATIONS OF ALLENES AND THEIR
APPLICATION TO THE TOTAL SYNTHESIS OF CLAVINE ALKALOIDS.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
The first section of this thesis describes the development of an enantioselective synthesis
of terminally unsubstituted methylenecyclopropanes. The key feature of this approach is a Rh2(STBPTTL)
4-mediated catalytic asymmetric cyclopropanation of unsubstituted allene to produce
enantioenriched methylenecyclopropanes bearing alkyl or activated ester functionalities. This
method was successfully applied to the enantioselective total synthesis of cycloclavine.
The second section of this thesis describes the development of an improved 12
steps/5.2% overall yield racemic total synthesis of the clavine alkaloid cycloclavine. The first
enantioselective total syntheses of the unnatural enantiomer (–)-cycloclavine and the natural
enantiomer (+)-cycloclavine were also accomplished in 8 steps/7.1%(brsm) overall yield and 8
steps/4% overall yield, respectively. Noteworthy features of this approach include a strainpromoted
intramolecular Diels-Alder reaction followed by a highly regioselective aerobic α,β-
dehydrogenation to form a key enone intermediate in >99.5:0.5 er after crystallization.
Additional noteworthy features include the enone 1,2-addition of a novel TEMPO-carbamate
aminomethyl carbanion and an IMDAF reaction to install the indole core. The mechanism of
thermolysis of the new TEMPOC amine protecting-group was investigated. Finally, the natural
and unnatural enantiomers were evaluated for their ability to bind to several neurotransmitter
receptors in radioligand binding assays.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
27 September 2018 |
| Date Type: |
Publication |
| Defense Date: |
4 May 2018 |
| Approval Date: |
27 September 2018 |
| Submission Date: |
10 June 2018 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
352 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Chemistry |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
total synthesis, cycloclavine, allene |
| Date Deposited: |
27 Sep 2018 19:56 |
| Last Modified: |
27 Sep 2019 05:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/34612 |
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