Solid-supported synthesis: From pharmacologically relevant heterocycles to biologically active surfaces

Vitaly V. Komnatnyy

Research output: Book/ReportPh.D. thesisResearch

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Abstract

The present PhD thesis consists of an introduction part and two separate parts covering selected research projects during the PhD study.
The introduction part describes the concept of solid-supported synthesis and combinatorial chemistry. The chapter covers recent achievements in materials for solid-phase synthesis, methods for on - and off-bead screening of combinatorial libraries and their applic ation to various biological targets.
The first part of the thesis is dedicated to the development of methodology for the synthesis of structurally diverse heterocyclic scaffolds via N-acyliminium intermediates on solid support. In Chapter 1.1, an intermolecular Mannich -type reaction of solid-supported N- acyliminium ions is reported. The method is useful for the solid -supported synthesis of substituted ?-lactames , which constitute a class of pharmacologically relevant small molecule scaffolds . Chapter 1.2, in turn, utilizes readily available ketones as precursors for solid-supported N-acyliminum ions. Under acidic reaction conditions, peptidic levulinamides undergo intramolecular ketone amide condensation reactions to form cyclic N-acyliminium intermediates, which in the presence of tethered nucleophiles bring about a second cyclization and the formation of a fused , bicyclic ring system.
The second part of the thesis deals with the topical problem of bacterial biofilm-related infections in manufacturing and use of indwelling medical devices, such as catheters and imp lants. . In Chapter 2.1, new methods for the controlled organo-functionalization of titanium, one of the most prominent materials in medicinal device industry, have been suggested . Initial acidic and oxidative treatment s of the metal surface genera te reactive hydroxyl moieties , which are subsequently modified with synthetically versatile amine -containing reagents. Subsequent applications in antimicrobial peptide synthesis, metal -catalysis, release from the surface, and polymer grafti ng, are also presented.
Original languageEnglish
Place of PublicationKgs. Lyngby
PublisherTechnical University of Denmark
Number of pages158
Publication statusPublished - 2012

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