I. A NEW SYNTHETIC APPROACH TO THE SYNTHESIS OF N-(PHOSPHONOACETYL)-L-ORNITHINE, II. THE INFLUENCE OF PYRIDINE ON THE OZONOLYSIS OF ALKENES

Authors

Bradley M. Johnson, University of Nebraska at LincolnFollow

Date of this Version

12-2010

Document Type

Article

Comments

A THESIS Presented to the faculty of The Graduate College at the University of Nebraska In Partial Fulfillment of Requirements For the Degree of Master of Science, Major: Chemistry, Under the Supervision of Professor Patrick H. Dussault. Lincoln, Nebraska: December 2010
Copyright 2010 Bradley M. Johnson.

Abstract

Part I. The use of chemical inhibitors to manipulate the level of amino acids in cells has proven to be invaluable in the mechanistic study of gene expression in bacteria and fungi. Here we present a new approach to the synthesis of δ‐N‐ (phosphonoacetyl)‐L‐ornithine (PALO), a potent ornithine transcarbamylase inhibitor, using a new amino acid protecting group, 9‐borabicyclononane (9‐BBN). Starting from commercially available reagents and utilizing mild reaction conditions, we were able to form PALO in fewer synthetic steps and in greater yields than previous attempts.

Part II. Ozonolysis is widely used to transform alkenes into oxygen‐rich functional groups (e.g.– alcohols, aldehydes, and acids). We were interested in the ability of Bronsted acids or bases to influence the reactivity of the carbonyl oxide intermediates in ozonolysis. Our preliminary investigations with a hydrogenbonding urea and a Bronsted base demonstrated absolutely no influence on the stereoselectivity of trapping of carbonyl oxides. However, we did observe that ozonolysis in the presence of pyridine greatly furnished significant amounts of aldehyde or ketone products at the expense of the expected ozonide. The enhanced formation of aldehydes or ketones was not observed for ozonolyses in the presence of an alcohol nucleophile, which resulted in the typical formation of hydroperoxyacetals.
There have been a number of anecdotal accounts describing the favorable influence of added pyridine on selective ozonolysis within polyunsaturated systems. We investigated the influence of pyridine and related molecules on the selectivity of ozonolysis for four dienes: citronellene, limonene, geranyl acetate, and 4‐vinyl‐1‐cyclohexene. The presence of pyridine was found to always enhance the selectivity for oxidative cleavage of the more electron‐rich alkene.

Adviser: Patrick H. Dussault