Copper-catalyzed arylation of 1,2-amino alcohols. Synthesis of N-terminal, peptide helix initiators, and characterization of highly helical, capped polyalanine peptides

I. An improved Ullmann reaction for N- or O-arylation of 1,2-aminoalcohols with aryl iodides is described. The procedures enjoy several advantages over traditional methods: a substoichiometric amount of copper catalyst is employed, the reactions take place in low boiling and non-toxic solvents such as isopropanol, the reactions occur at relatively low temperatures, and a variety of non-activated aryl iodide substrates may be used. II. Recent advances in solubilization of polyalanine and helix stabilization by end capping were combined to synthesize a series of highly helical, water-soluble polyalanine peptides permitting straightforward context-free investigation of this most common helix- forming [alpha]-amino acid. Three types of peptides incorporating this helical polyalanine region were made, each for a specific purpose: structure determination by NMR; fractional helicity measurement by amide NH to ND exchange in D₂0, observed by NMR; and CD analysis. CD spectra of these helical peptides were used to directly verify an equation used for peptide structural analysis. The helix-initiating N-terminal cap (Hel) used to create the highly helical polyalanines is a synthetically modified Pro-Pro dipeptide. Hel was developed in the Kemp group a decade ago, and peptides created with it have been extensively studied in this group. However, the 18-step synthesis of Hel has hindered its use by others. Therefore, simpler analogs of Hel have been made and preliminary studies have been conducted. The simpler N-caps were synthesized in twelve steps or fewer and proved effective at helix initiation, as judged by CD spectroscopy.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Chemistry

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2005

Author dc:creator

• Job, Gabriel Ethan

Advisor dc:contributor.advisor

• Daniel S. Kemp.

• Chemistry.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/32481

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/32481