Asymmetric syntheses of β- and γ-amino acids

Thesis

This thesis is concerned with the development of new synthetic routes for the asymmetric syntheses of a range of β- and γ-amino acids.

Chapter 1 introduces the various biological activities displayed by cyclic β-amino acid containing compounds together with their occurrence in pharmaceutical molecules and β-peptides. Some of the most commonly used synthetic strategies for the preparation of carbocyclic β-amino acids are briefly described, with the focus on the formation and functionalisation of a five-membered carbocyclic ring.

Chapter 2 describes a full investigation into a highly diastereoselective Ireland-Claisen rearrangement of stereodefined allyl β-amino esters to access enantiopure α-substituted β-amino acid products. The synthetic utility of this methodology is highlighted by its application in the asymmetric syntheses of five previously inaccessible C(5)-substituted 1,2-anti-1,5-syn-transpentacins.

Chapter 3 delineates investigations into a highly diastereoselective conjugate additionelimination protocol for the preparation of a cyclic β'-amino-α,β-unsaturated ester. Subsequent chemo- and diastereoselective conjugate addition reactions of Grignard reagents and lithium amides to this substrate enabled the asymmetric syntheses of four C(5)-substituted 1,2-anti-1,5-syn-transpentacins and two five-membered β,β'-diamines.

Chapter 4 details the extension of the protocol developed in Chapter 3 for the conjugate addition of Grignard reagents to a range of acyclic γ-(N,N-dibenzylamino)-substituted α,β-unsaturated esters. Elaboration of the β,γ-disubstituted γ-amino ester products culminated in the asymmetric syntheses of six β,γ-disubstituted γ-amino acids.

Chapter 5 chronicles the preparation of an azabicyclic α,β-unsaturated ester, following which attempts towards the asymmetric synthesis of various substituted pyrrolizidines using a conjugate addition protocol are subsequently described.

Chapter 6 contains full experimental procedures and characterisation data for all compounds synthesised in Chapters 2, 3, 4 and 5.

Authors: Zammit, C

• Publication date: 2015
• DOI: 10.5287/ora-2azg8dzkz
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: methodology; organic chemistry; asymmetric synthesis; organic synthesis; amino acid synthesis; synthetic organic chemistry
• Subjects: Polymers Amino acid and peptide chemistry; Physical Sciences; Organic synthesis; Synthetic organic chemistry; Chemistry & allied sciences; Organic chemistry