Stereospecific enrichment of heterocyclic enantiomers

Abstract

The present invention describes methods for the stereoselective synthesis of heterocyclic enantiomers. The methods of the present invention incorporate the stereo-preferred oxidation of quinolone thiomethyl intermediates by optically active camphor based oxaziridines to provide R(+) or S(−) quinolone methylsulfinyl derivatives.

1 . A method, comprising: 
 a) providing: i) a flosequinan racemate; ii) triphenylphosphine; and    b) reacting, in a solvent, said flosequinan racemate with said triphenylphosphine under conditions such that a racemic mixture of 7-fluoro-1-methyl-3-methylthio-4-quinolone is produced.    
   
   
       2 . The method of  claim 1 , wherein said solvent is selected from the group consisting of carbon tetrachloride and a mixture of xylene and carbon tetrabromide.  
   
   
       3 . The method of  claim 1 , further comprising: 
 c) treating said racemic mixture of 7-fluoro-1-methyl-3-methylthio-4-quinolone with (1R)-(−)-(10-camphorsulfonyl)oxaziridine under conditions such that R-(+)-flosequinan is produced in enantiomeric excess.    
   
   
       4 . A method, comprising: 
 a) providing: i) a flosequinan racemate; ii) triphenylphosphine; and    b) reacting, in a solvent, said flosequinan racemate with said triphenylphosphine under conditions such that a racemic mixture of 7-fluoro-1-methyl-3-methylthio-4-quinolone is produced.    c) treating said racemic mixture of 7-fluoro-1-methyl-3-methylthio-4-quinolone with (1S)-(+)-(10-camphorsulfonyl)oxaziridine under conditions such that S-(−)-flosequinan is produced in enantiomeric excess.