The Asymmetric Synthesis of beta-Amino Acids

Tomanek, Richard (1988) The Asymmetric Synthesis of beta-Amino Acids. PhD thesis, University of Glasgow.

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Abstract

Whereas the asymmetric synthesis of alpha-amino acids has attracted considerable attention in recent years, there have been relatively few published investigations into the asymmetric synthesis of 6-amino acids. It was the aim of the work described in this thesis to devise an improved asymmetric synthesis of beta-amino acids involving the construction of heterocyclic intermediates in a diastereoselective manner via the 1,3-dipolar cycloaddition reactions of chiral nitrones with suitably functionalised alkenes. The Introduction reviews the natural occurrence of the more abundant 6-amino acids, previous asymmetric syntheses of 6-amino acids and the mechanism and stereochemistry of 1,3-dipolar cycloaddition reactions of nitrones. Chapter 1 describes the synthesis of the chiral and achiral nitrones used in the cycloaddition reactions described in this thesis. Chapter 2 describes an investigation into an asymmetric synthesis of 6-amino acids via, 1,3-dipolar cycloaddition reactions of nitrones with diethyl ethylidene - and methylidenemalonate. Nitrones (9), (10) and (28) have been shown to react regiospecifically with diethyl ethylidene-malonate and ethyl crotonate, while reactions between nitrones (9), (10) and (5) and diethyl methylidenemalonate afforded regioisomeric product mixtures. The reaction between nitrone (6) and diethyl methylidenemalonate was also shown to proceed regiospecifically [Scheme I]. Chapter 3 describes the non-asymmetric synthesis of N-phenyl-beta-phenyl-beta-alanine (97) via the cycloaddition of C,N-diphenylnitrone (9) with ketene acetal (91) and the subsequent hydrogenolysis of the adduct (96) thus formed [Scheme II]. Chapter 3 also describes the synthesis of three chiral ketene acetals. The asymmetric syntheses of beta-phenyl-beta-alanine (154), beta-leucine (157) and isoxazolidinones (162,163) which may lead to beta-tyrosine are described in Chapter 4. They depend upon the reaction of chiral nitrones with alpha-chloro-acrylonitrile to afford isoxazolidines in which the substituents have been placed in a regio- and stereoselective manner on the preriphery of the 5-membered ring. Subsequent hydrolysis afforded isoxazolidin-5-ones which were hydrogenolysed to afford free beta-amino acids [Scheme III]. asymmetric synthesis of Thienamycin. Isoxazolidinone (193) was obtained as a single diastereomer and converted to olefin 199) via diol (195) and thionocarbonate (197) [Scheme IV].

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Organic chemistry, Biochemistry
Date of Award: 1988
Depositing User: Enlighten Team
Unique ID: glathesis:1988-77722
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jan 2020 11:53
Last Modified: 14 Jan 2020 11:53
URI: http://theses.gla.ac.uk/id/eprint/77722

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