An approach to the production of tethered gbs-turn peptidomimetics by geminal acylation

McCarthy, Anne Marie (2004) An approach to the production of tethered gbs-turn peptidomimetics by geminal acylation. Masters thesis, Memorial University of Newfoundland.

[English] PDF - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. Download (36MB)

Abstract

The aim of this research was to develop a synthetic route to produce 5,6-fused-l-aza-2-oxobicycloalkane amino acids. Geminal acylation of a ketone or its acetal provides ready access to a 2,2-disubstituted 1,3-cyclopentanedione derivative. Double geminal acylation of diketones with long acyclic tethers between the carbonyls is envisaged as a core strategy for the development of synthetic access to tethered peptidomimetics. The focus of this research was to develop a route to 5,6-fused-1-aza-2-oxobicycloalkane amino acids which are β-turn peptidomimetics, with carbon-based bridgehead substituents. Geminal acylation of the acetal derived from hexadeca-1,15-diene-5,12-dione gave the 1,3-cyclopentanedione 52 in 29% yield along with numerous interesting side-products. A successful route to form lactams via Beckmann rearrangement was established. The development of this synthetic route, including the elucidation of the structures of side-products, is discussed in detail.

Actions (login required)

View Item