Clarithromycin (6-methoxyerythromycin) is a macrolide antibiotic active against a broad range of Gram positive bacteria. Clarithromycin was designed to enhance acid stability and improve oral bioavailability compared with erythromycin which is highly unstable to acidic conditions, undergoing a series of internal ketalisations between the 9-keto moiety and alcohols at C6 and C11. Omura and colleagues found that protection of the labile 6-OH group by methylation provided a simple but elegant solution.