Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.278865
Title: Studies of alkylcobaloximes as models for a B₁₂-dependent rearrangement
Author: Kibende, Samson Mwesigye
ISNI:       0000 0001 3438 5197
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 1983
Availability of Full Text:
Access from EThOS:
Access from Institution:
Abstract:
The necessity for vitamin B12 in animals and the consequences of lack of it are well-documented in the literature. Its unique and indispensable role, and its active form as the coenzyme for at least eleven different enzymic rearrangements in vivo, are also known. The enzymic conversion of a-MG to MelT, which is the centre of interest in the present work, is one of these rearrangements. However, the mechanism by which most of these rearrangements proceed is still a matter of speculation, based on logic and inconclusive experimental observations. Organocobalt model systems, which resulted from the suggestion that substrate-Co species are intermediates in these rearrangements, have been synthesised and studied in their thousands by various workers, and have in some instances shed light on this intriguing mechanistic problem. This thesis is a description of the synthesis, characterisation and rearrangement of monocarboxylate-substituted but-3-enyl- and cyclopropylmethyl(pyridine)- cobaloximes, in a model study of the B^2-dePendent enzymic rearrangement of a-MG. The syntheses of the alkylating agents are described, and novel compounds, which are fully characterised, are reported. The findings from this study suggest that alkyl-cobalamins postulated as intermediates in the reaction catalysed by a-MG mutase would be insufficiently reactive towards rearrangement. However, rapidly interconverting carboxy-substituted but-3-enyl and cyclopropylmethyl radicals are suggested to be plausible intermediates. An addenda to this thesis contains synthetic proposals for the continuation of this work. A separate chapter (Chapter 5) describes the preparation and testing of the cyclic analogues of the antitumour drug busulphan, cis- and trans-di(hydroxymethyl)cyclopropane dimethanesulphonate. Both compounds showed little antitumour activity near their toxic dose. The implications of these observations for the mode of action of busulphan are discussed.
Supervisor: Not available Sponsor: European Research Council ; Government of Uganda
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.278865  DOI: Not available
Keywords: QD Chemistry
Share: