Studies on the biosynthesis of the various subunits of neomycins
Studies on the biosynthesis of the various subunits of neomycins
This thesis is concerned with the elucidation of the mechanism of the formation of the various subunits of neomycins B and C. The first target was to study the epimerization process at C-5 of D-glucose during its incorporation into the neosamine B ring of neomycin B. For this purpose an unambiguous, new method for the preparation of [5-3H] glucose was developed and using this labelled species it was found that most of the tritium (90% ) from the 5-position of the glucose was lost during conversion into the neosamine B moiety. These results suggest that the epimeric centre at C-5 of the neosamine B ring is produced through an enolization process involving a carbonyl group at either C-4 or C-6. The involvement of C-4 was eliminated by demonstrating that the 3H at C-4 of [3,4-3H] D-glucose was incorporated intact into neosamine B. On the bases of these results a reaction sequence for the epimerization process is suggested. The second problem investigated in this thesis is regarding the pathway for the biosynthesis of the 2-deoxystreptamine ring of neomycins. Four compounds expected to be involved in this pathway were prepared and used for the incorporation experiments. These compounds are [6-3H]6-deoxy-5-keto-D-glucose, [5,6-3H]6-deoxy-D-glucose, 2-deoxyscylloinosose and viboquercitol. The results show that 6-deoxysugar derivatives are incorporated into 2-deoxystreptamine suggests that the elimination of the unwanted C-6 hydroxyl group of D-glucose occurs prior to or during the cyclization process. In order to shed further light on the biosynthesis of 2-deoxystreptamine, we investigated whether C-3, C-4 and C-5 are involved in this process by using [3-3H]; [4-3H]; [5-3H] D-glucose. The results from these experiments showed that the 3H atoms at C-4 and C-5 of D-glucose are lost during the biosynthesis of 2-deoxystreptamine. On the other hand, the C-3 tritium of D-glucose was retained at C-5 of 2-deoxystreptamine. The loss of C-4 tritium of D-glucose implies that C-4 of D-glucose must be involved in the biosynthesis of 2-deoxystreptamine either by conversion into a carbonyl group which is necessary for the enhancement of the acidity of C-5 hydrogen during the elimination of the unwanted -OH group at C-6 or formation of a C-4 - C-5 endiol intermediate. The elimination of the C-5 tritium of D-glucose is in accord with the notion that C-5 of D-glucose is converted to the C-3 amino group of 2-deoxystreptamine via a carbonyl intermediate. The above results were used to suggest detailed reaction sequence for the biosynthesis of 2-deoxystreptamine. (D73650/87)
University of Southampton
1986
Goda, Sayed Kamel Ahmed
(1986)
Studies on the biosynthesis of the various subunits of neomycins.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
This thesis is concerned with the elucidation of the mechanism of the formation of the various subunits of neomycins B and C. The first target was to study the epimerization process at C-5 of D-glucose during its incorporation into the neosamine B ring of neomycin B. For this purpose an unambiguous, new method for the preparation of [5-3H] glucose was developed and using this labelled species it was found that most of the tritium (90% ) from the 5-position of the glucose was lost during conversion into the neosamine B moiety. These results suggest that the epimeric centre at C-5 of the neosamine B ring is produced through an enolization process involving a carbonyl group at either C-4 or C-6. The involvement of C-4 was eliminated by demonstrating that the 3H at C-4 of [3,4-3H] D-glucose was incorporated intact into neosamine B. On the bases of these results a reaction sequence for the epimerization process is suggested. The second problem investigated in this thesis is regarding the pathway for the biosynthesis of the 2-deoxystreptamine ring of neomycins. Four compounds expected to be involved in this pathway were prepared and used for the incorporation experiments. These compounds are [6-3H]6-deoxy-5-keto-D-glucose, [5,6-3H]6-deoxy-D-glucose, 2-deoxyscylloinosose and viboquercitol. The results show that 6-deoxysugar derivatives are incorporated into 2-deoxystreptamine suggests that the elimination of the unwanted C-6 hydroxyl group of D-glucose occurs prior to or during the cyclization process. In order to shed further light on the biosynthesis of 2-deoxystreptamine, we investigated whether C-3, C-4 and C-5 are involved in this process by using [3-3H]; [4-3H]; [5-3H] D-glucose. The results from these experiments showed that the 3H atoms at C-4 and C-5 of D-glucose are lost during the biosynthesis of 2-deoxystreptamine. On the other hand, the C-3 tritium of D-glucose was retained at C-5 of 2-deoxystreptamine. The loss of C-4 tritium of D-glucose implies that C-4 of D-glucose must be involved in the biosynthesis of 2-deoxystreptamine either by conversion into a carbonyl group which is necessary for the enhancement of the acidity of C-5 hydrogen during the elimination of the unwanted -OH group at C-6 or formation of a C-4 - C-5 endiol intermediate. The elimination of the C-5 tritium of D-glucose is in accord with the notion that C-5 of D-glucose is converted to the C-3 amino group of 2-deoxystreptamine via a carbonyl intermediate. The above results were used to suggest detailed reaction sequence for the biosynthesis of 2-deoxystreptamine. (D73650/87)
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Published date: 1986
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Local EPrints ID: 461006
URI: http://eprints.soton.ac.uk/id/eprint/461006
PURE UUID: d0d35ee6-184b-4805-b3d7-b40055ea302e
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Date deposited: 04 Jul 2022 18:33
Last modified: 04 Jul 2022 18:33
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Author:
Sayed Kamel Ahmed Goda
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