2- Hydroxy-6- from Aspergillus oryzae

Dihydroisoxazole 1066 is obtained in nearly quantitative yield from the cycloaddition of ethyl methacrylate with ethoxycarbonylformonitrile oxide. Treatment of 1066 with protease from Aspergillus oryzae in a two-phase system (toluene and pH 7.0 buffer) results in an enantio-selective hydrolysis of the 5-carboxylate group, producing a mixture of (/ )-1067 (44.5% yield, 97% ee) and (5)-1068 (55% yield, 77% ee) when the reaction is terminated at 55% conversion. Hydrolysis of the diester 1067 and thermal decarboxylation of the resulting diacid (1069) affords (i )-3-cyano-2-hydroxy-2-methylpropanoic acid (1070). Acid catalyzed methanolysis of the nitrile group gives 1059 with > 97% ee. 

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