Multisite Modification of Neomycin B: Combined Mitsunobu and Click Chemistry Approach
Author(s)
Quader, Sabina
Boyd, Sue E
Jenkins, Ian D
Houston, Todd A
Year published
2007
Metadata
Show full item recordAbstract
The aminoglycoside antibiotic neomycin B has been converted into several novel building blocks that can be used for the specific modification of three of the four ring systems. Under carefully controlled conditions, the Mitsunobu reaction can be used to selectively dehydrate the ido ring to give the talo epoxide, not a tricyclic aziridine-azetidine structure as has been claimed previously. Subsequently however, under more forcing conditions, the 2-deoxy streptamine ring undergoes Mitsunobu dehydration to give an aziridine. An unusual remote neighbouring group effect was observed. When the primary hydroxyl of the ribose ring ...
View more >The aminoglycoside antibiotic neomycin B has been converted into several novel building blocks that can be used for the specific modification of three of the four ring systems. Under carefully controlled conditions, the Mitsunobu reaction can be used to selectively dehydrate the ido ring to give the talo epoxide, not a tricyclic aziridine-azetidine structure as has been claimed previously. Subsequently however, under more forcing conditions, the 2-deoxy streptamine ring undergoes Mitsunobu dehydration to give an aziridine. An unusual remote neighbouring group effect was observed. When the primary hydroxyl of the ribose ring was blocked, aziridine formation on the deoxystreptamine ring did not occur. Both the epoxide and epoxide-aziridine neomycin building blocks can be ring-opened with azide, and subjected to "click" type chemistry with terminal alkynes to generate a series of new neomycin analogues. These reactions can all be carried out without recourse to O-protecting groups. A detailed conformational analysis by NMR revealed some unexpected conformer preferences in these systems.
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View more >The aminoglycoside antibiotic neomycin B has been converted into several novel building blocks that can be used for the specific modification of three of the four ring systems. Under carefully controlled conditions, the Mitsunobu reaction can be used to selectively dehydrate the ido ring to give the talo epoxide, not a tricyclic aziridine-azetidine structure as has been claimed previously. Subsequently however, under more forcing conditions, the 2-deoxy streptamine ring undergoes Mitsunobu dehydration to give an aziridine. An unusual remote neighbouring group effect was observed. When the primary hydroxyl of the ribose ring was blocked, aziridine formation on the deoxystreptamine ring did not occur. Both the epoxide and epoxide-aziridine neomycin building blocks can be ring-opened with azide, and subjected to "click" type chemistry with terminal alkynes to generate a series of new neomycin analogues. These reactions can all be carried out without recourse to O-protecting groups. A detailed conformational analysis by NMR revealed some unexpected conformer preferences in these systems.
View less >
Journal Title
Journal of Organic Chemistry
Volume
72
Publisher URI
Subject
Medicinal and biomolecular chemistry
Organic chemistry