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Title: Exploring novel linkers for solid phase organic synthesis
Author: Gordon, K. H.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2001
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Solid phase organic synthesis is an area of synthesis chemistry which is being exploited in the search for new biologically active compounds by combinatorial techniques. Chapter 1 of this thesis introduces the key concepts of solid phase methodology and combinatorial synthesis with particular focus on the issues that concern the invention of linkers which are used to attach the substrate to the solid support. Studies on linkers for the synthesis and traceless release of β-lactams are described in Chapters 2 and 3. Utilisation of Sieber amide resin for traceless β-lactam synthesis is described. An approach based on a novel benzyloxyaniline linker, which uses ceric ammonium nitrate as a cleavage reagent, is discussed. The chemistry of the cleavage reaction was studied on solid phase and is exemplified by the release of small arrays of β-lactams and acyclic secondary amides. In Chapter 4, a novel safety catch linker utilising sulfoxide pyrolysis as a cleavage mechanism is explored. The linker incorporates a thioether which is activated for cleavage by oxidation to its sulfoxide. Studies on the synthesis and activation of the linker in solution and on solid phase are discussed. The pyrolytic cleavage reaction of the linker was investigated on solid phase and is demonstrated by the preparation and release of an array of β-sultams. A study on a chiral linker based on the Garner aldehyde, which is a chiral synthon widely used in synthesis, is described in Chapter 5. The synthesis of the solid phase linker, which incorporates an N,O-di-protected chiral oxazolidine aldehyde, is described in solution and on solid phase and an investigation to confirm the stereochemical purity of the linker is discussed. The linker is exemplified by the stereoselective synthesis of an array of chiral 1,3,4-substituted β-lactams.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available