Kibende, Samson Mwesigye (1983) Studies of alkylcobaloximes as models for a B12-dependent rearrangement. PhD thesis, University of Warwick.

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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, viz., oia— and trans-di(hydroxymethyUcyclopropane 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.

Item Type:	Thesis (PhD)
Subjects:	Q Science > QD Chemistry
Library of Congress Subject Headings (LCSH):	Cobaloximes -- Synthesis, Organocobalt compounds, Vitamin B12, Antineoplastic agents
Official Date:	1983
Dates:	Date Event 1983 UNSPECIFIED
Institution:	University of Warwick
Theses Department:	Department of Chemistry and Molecular Sciences
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Golding, Bernard, T.
Sponsors:	European Research Council ; Uganda. Government
Extent:	xiii, 169 leaves : illustrations
Language:	eng

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