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DOI: 10.1055/s-0030-1258872
Synthesis of (R)-Ofloxacin
Contributor(s):Philip KocienskiRWTH Aachen and Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany
Asymmetric Metal-Free Synthesis of Fluoroquinolones by Organocatalytic Hydrogenation
Tetrahedron 2010, 66: 6565-6568
Publication History
Publication Date:
22 November 2010 (online)
Key words
(R)-ofloxacin - flumequine - fluoroquinolones - organocatalysis - Brønsted acid catalyzed transfer hydrogenation
Significance
The key step in the small-scale synthesis of (R)-ofloxacin depicted here is the first step, a chiral Brønsted acid catalyzed transfer hydrogenation in which the hydride source is the dihydropyridine C. These reactions give excellent enantiofacial discrimination with low catalyst loadings under mild conditions. A synthesis of the simpler fluoroquinolone antibiotic flumequine is also described.
Comment
Ofloxacin is a DNA gyrase inhibitor that was initially marketed as a racemate. The (S)-(-)-enantiomer, levofloxicin, is more active than the (R)-enantiomer and has now supplanted the racemate for the treatment of life-threatening bacterial infections.
Review: For a review about asymmetric Brønsted acid catalyzed transfer hydrogenations, see: M. Rueping, E. Sugiono, F. R. Schoepke Synlett 2010, 852-865.