Stephenson, Corey Robert John
(2005)
NOVEL CASCADE REACTIONS OF ALKENYLZIRCONOCENES AND THEIR APPLICATION TO THE SYNTHESIS OF CYCLOPROPYL PEPTIDE MIMETICS.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
We have successfully applied to Zr→Zn methodology developed in the Wipf group to the preparation of functionalized allylic amides and alcohols via the 1,2-addition to imines and α-keto esters. During the preparation of allylic amides, concomitant formation of C-cyclopropylalkylamides was observed in CH₂Cl₂. The combination of the Zr→Zn methodology with the Simmons-Smith cyclopropanation reaction has led to the discovery of a novel cascade reaction for the preparation of C,C-dicyclopropylmethylamides from simple, readily available starting materials. These functionalized amides have served as precursors in a diversity-oriented approach for the preparation of 7-, 8-, and 9-membered azaspirocyclic ring structures based on reductive amination, epoxide opening or ring-closing metathesis strategies. Finally, a small library of α,β-cyclopropyl-γ-amino acids were prepared in 6-7 steps from readily available starting materials and evaluated for their potential as peptide mimetics. Simple amide derivatives were found to adopt stable sheet-like structures in the solid state, whereas the structural properties of oligopeptides were not readily assessed using crystallographic techniques. A combination of molecular modeling, circular dichroism and NMR studies was used to ascertain the solution folding preferences of our novel peptides.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
6 June 2005 |
| Date Type: |
Completion |
| Defense Date: |
8 December 2004 |
| Approval Date: |
6 June 2005 |
| Submission Date: |
3 January 2005 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| 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: |
bicyclobutane; bicyclo[1.1.0]butane; transmetalation |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-01032005-185046/, etd-01032005-185046 |
| Date Deposited: |
10 Nov 2011 19:30 |
| Last Modified: |
15 Nov 2016 13:35 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/6250 |
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