Synthesis of (R)-Ofloxacin

(R)-ofloxacin - flumequine - fluoroquinolones - organocatalysis - Brønsted acid catalyzed transfer hydrogenation

Significance

<P>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.</P>

Comment

<P>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.</P><P> Review: For a review about asymmetric Brønsted acid catalyzed transfer hydrogenations, see: M. Rueping, E. Sugiono, F. R. Schoepke Synlett 2010, 852-865.</P>