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Formation, isolation and characterization of an AB-biaryl atropisomer of oritavancin |
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| Authors: | Casey Chun Zhou Eric J Stoner Kent D Stewart L Steven Hollis Edmund D Matayoshi Gregory M Brill |
| Institution: | a D-R418, Structural Chemistry, Global Pharmaceutical Research and Development, Abbott Laboratories, 1401 Sheridan Road, North Chicago, IL 60064-4000, USA b D-R450, Process Chemistry, Global Pharmaceutical Research and Development, Abbott Laboratories, North Chicago, IL 60064-4000, USA c D-R45T, Process Analytical Chemistry, Global Pharmaceutical Research and Development, Abbott Laboratories, North Chicago, IL 60064-4000, USA d D-R46Y, Structural Biology, Global Pharmaceutical Research and Development, Abbott Laboratories, North Chicago, IL 60064-4000, USA |
| Abstract: | Oritavancin is a semi-synthetic glycopeptide antibiotic which is structurally related to vancomycin. When oritavancin bisphosphate is dried in vacuo with heat, a new compound forms. This new compound is stable only in the solid state and reverts to oritavancin in solution. Highly enriched samples of this compound were obtained by preparative HPLC and the structure of this compound was elucidated by using one and two-dimensional (1H and 13C) NMR spectroscopy in conjunction with computer-assisted molecular modeling. It has been determined that oritavancin adopts a conformation similar to that of vancomycin in solution, while the new compound is the unnatural R-AB-biaryl atropisomer of oritavancin. This is the first observation and isolation of an AB-biaryl atropisomer in an intact member of the vancomycin family of glycopeptide antibiotics. |
| Keywords: | Atropisomer Oritavancin NMR Antibiotic Vancomycin Glycopeptide |
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