Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

NOVEL CASCADE REACTIONS OF ALKENYLZIRCONOCENES AND THEIR APPLICATION TO THE SYNTHESIS OF CYCLOPROPYL PEPTIDE MIMETICS

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 (Unpublished)

[img]
Preview
PDF
Primary Text

Download (4MB) | Preview

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.


Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Stephenson, Corey Robert Johncorey@alumni.uwaterloo.ca
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWipf, Peterpwipf@pitt.eduPWIPF
Committee MemberMokotoff, Michaelmoagie@pitt.eduMOAGIE
Committee MemberFloreancig, Paulflorean@pitt.eduFLOREAN
Committee MemberNelson, Scottsgnelson@pitt.eduSGNELSON
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

Metrics

Monthly Views for the past 3 years

Plum Analytics


Actions (login required)

View Item View Item