MAGNETIC RESONANCE IN CHEMISTRY, VOL, 30, 1241-1246 (1992) zyxwvu Structural Studies on Clarithromycin (6-O-Methylerythromycin A) zyx : Assignments of the 'H and 13C N M R Spectra in Organic and Aqueous Solutions Abida Awan, Jill Barber* and Richard J. Brennan Department of Pharmacy, University of Manchester, Manchester M13 9PL, UK John A. Parkinson Department of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 zyxwv 355, UK Full assignments of the 'H and 13C NMR spectra of clarithromycin (6-O-methylerythromycin A) in CDCI, and buffered D,O were carried out. In contrast to erythromycin A, clarithromycin exists as a single isomer, the 9-ketone, in aqueous solution. KEY WORDS 'H NMR I3C NMR Clarithromycin 6-O-Methyierythromycin A INTRODUCTION Clarithromycin (1) is an antibiotic of the erythromycin group with some improved clinical properties over the parent compound.' We have previously published assignments of the NMR spectra of erythromycin A showing that in aqueous solution this drug consists of two slowly interconverting i ~ o m e r s . ~ . ~ These isomers were identified as the 9-ketone (2a) and the 9,12-hemi- acetal (2b). We and others4 have shown that a similar mixture obtains in DMSO-d,, except that a third isomer identified as the 6,9-hemiaceta14 is also present, in very small amounts. The work described here was aimed at assigning the 'H and 13C NMR spectra of clarithromycin in CDCI, (in which erythromycin exists almost exclusively as 2a) and in D 2 0 buffer. The identities and proportions of the different isomers in aqueous solution were of special interest. HO 15 zyxwvuts O 7" zyxw 6" zyxwv 2 3 2h RESULTS Assignments of NMR spectra CDCI, solution. Clarithromycin is much more soluble than the parent drug in chloroform. A solution of 60 mg 0749-1 zyxwvutsrq 58 1/92/12 1241-06 $08.00 0 1992 by John Wiley & Sons, Ltd. zyxwvuts Received 8 June 1992 Accepted 4 August 1992