Multisite modification of neomycin B: combined Mitsunobu and click chemistry approach.

Abstract

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. Subsequently however, under more forcing conditions, the 2-deoxy streptamine ring undergoes Mitsunobu dehydration to give an aziridine. An unusual remote neighboring 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.

• Authors: Sabina Quader, Sue E Boyd, Ian D Jenkins, Todd A Houston
• Journal: The Journal of organic chemistry (J Org Chem) Vol. 72 Issue 6 Pg. 1962-79 (Mar 16 2007) ISSN: 0022-3263 [Print] United States
• PMID: 17298096 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aziridines
• Epoxy Compounds
• Framycetin

Topics

• Aziridines
• Epoxy Compounds
• Framycetin (chemistry)
• Magnetic Resonance Spectroscopy
• Molecular Conformation