Enantiomeric Enrichment in the Hydrolysis of Oxazolones Catalyzed by Cyclodextrins or Proteolytic Enzymes

Article abstract of DOI:10.1021/ja00530a047

Five 5(4H)-oxazolones bearing substituents of variable hydrophobicity and bulkiness in positions 2 and 4 have been hydrolyzed in the presence of the proteolytic enzymes chymotrypsin and subtilisin or the α- and β-cyclodextrins.The acylamino acids produced are partially deracemized.With the enzymes, an appreciable enantiomeric enrichment is obtained only when both substituents are relatively bulky; the enantioselectivities are nevertheless quite low for enzymic reactions.With chymotrypsin, an enantiomeric excess of 76percent in favor of the L isomer is observed in the hydrolysis of the 2-phenyl-4-benzyloxazolone and of 30percent in favor of the D for the 2-phenyl-4-(2-carboxamidoethyl)oxazolone.There is a general inversion of stereoselectivity between chymotrypsin and subtilisin.The hydrolysis in the presence of cyclodextrin is a multistep process with formation of an acylcyclodextrin intermediate concurrent with hydrolysis.The substituent in position 2 plays an important role in controlling the enantioselectivity.When this substituent is a phenyl, the L acylamino acid is the predominant product with an enantiomeric excess of the order of 60percent.When there is a methyl in position 2, the direction of asymmetric induction is reversed or the optical yield is close to zero.