Determination of the stereochemistry of anhydroerythromycin A, the principal degradation product of the antibiotic erythromycin A

Organic & Biomolecular Chemistry
Addolreza HassanzadehJill Barber

Abstract

Anhydroerythromycin A arises from the acid-catalysed degradation of erythromycin A both in vitro and in vivo. It has negligible antibacterial activity, but inhibits drug oxidation in the liver, and is responsible for unwanted drug-drug interactions. Its structure has 18 chiral centres common with erythromycin A, but C-9 (the spiro carbon) is also chiral in anhydroerythromycin and its stereochemistry has not previously been reported; both 9R- and 9S-anhydroerythromycin A are plausible structures. An understanding of the chirality at C-9 was expected to throw light on the mechanism of acid-catalysed degradation of erythromycin A, a subject that has been debated in the literature over several decades. We now report a determination of the three-dimensional structure of anhydroerythromycin A, including the stereochemistry at C-9, by NMR and molecular modelling. In parallel, the relative stereochemistry of anhydroerythromycin A 2'-acetate was determined by X-ray crystallography. Both compounds were shown to have 9R stereochemistry, and anhydroerythromycin A exhibited considerable conformational flexibility in solution.

References

Nov 1, 1985·Antimicrobial Agents and Chemotherapy·I O KibwageG Levol

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Citations

May 16, 2008·Organic & Biomolecular Chemistry·Manikandan KadirvelElena V Bichenkova
Oct 2, 2015·Beilstein Journal of Organic Chemistry·Ana ČikošSulejman Alihodžić
Sep 21, 2007·The Journal of Physical Chemistry. a·Abdolreza HassanzadehPeter A Gorry

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