Sustainable Methodology for the Synthesis of Amides, Esters and Polypropionate Fragments

  • Robert Chapman

Student thesis: Doctoral ThesisPhD

Abstract

This thesis presents research into the development of sustainable methodology for the synthesis of amides, esters and polypropionate fragments. As well as a literature review of efficient natural product synthesis. Acylals are a known class of reagent that have been utilized within literature for a wide range of synthetic methodologies. Herein we present acylals as new highly active reagents for the N-/O-acylation of amines and alcohol nucleophiles for the synthesis of a range of formamides, acetamides, formate esters and acetate esters. It has been demonstrated that a range of acyl groups can be transferred including short and long chain alkyls, acryloyl, benzoyl, phenyl acetyl and biologically important trifluoroacetyl group, thus enabling the synthesis of a range of benzylamides and esters. These acylation reagents have also been shown to demonstrate inherent N-/O- selectivity towards the amine and alcohol groups of serine methyl ester. The scope and limitations of these reagents of the use of acylals has been investigated through the N-formylation of a range of unprotected amino acids, and for the synthesis of the biologically important tripeptide f-MLP. As well as the acylation/formylation of the ω-amino residue of a lysine residue within a decapeptide. Finally, it has also been demonstrated that a simple switch in pH from basic to acidic conditions for diols can change from O-acylation to acetal formation.The synthesis of enantiomerically enriched dihydropyrans from the heteo-Diels-Alder reaction of 1-alkoxy dienes and ethyl glyoxalate has been presented. A series of stereoselective derivatisation reactions were developed including, hydroboration, hydrogenation, epoxidation, dihydroxylation and epimerization which procced with stereoselectivity to afford a range of complex enantiomerically enriched polypropionate based building blocks, which are ideally suited for the synthesis of polyketide natural products through a “plug and play” approach. Chemistry has also been presented which makes use of the orthogonally addressable synthetic handles of the pyran building blocks. Utilization of either the masked aldehyde character or the ester functionality present allows for further elaboration of the pyran building blocks by selectively introducing new functionality.
Date of Award26 Apr 2017
Original languageEnglish
Awarding Institution
  • University of Bath
SupervisorPawel Plucinski (Supervisor), Steven Bull (Supervisor) & Matthew Jones (Supervisor)

Cite this

Sustainable Methodology for the Synthesis of Amides, Esters and Polypropionate Fragments
Chapman, R. (Author). 26 Apr 2017

Student thesis: Doctoral ThesisPhD