APPROACHES TO CHEMICALLY MODIFIED ENZYMES AS SYNTHETIC CATALYSTS

Attempts to introduce new catalytic activities of potential use in synthetic transformations into enzyme active sites are described. Substitution of the naturally occurring zinc in carboxypeptidase A by several metals known to catalyse hydrogenation was investigated; a new protein characterised as a rhodium carboxypeptidase was isolated but it failed to show activity as a hydrogenation catalyst for the reduction of a series of dehydroamino acid amides. Horse liver alcohol dehydrogenase was investigated for its potential to act as an oxygen transferase via Lewis acid catalysis. A series of cyclohexenyl and phenylribosides together with new alkenyl(arenyl)oxymethylenoxyethanols was prepared for evaluation as substrates; in the course of this study, novel neighbouring group participation by the oxygen atom of a chloromethyl ether was observed. Although the binding of potential oxygen acceptors (alkenes and aromatic compounds) and oxygen donors (hydrogen peroxide and alkyl hydroperoxides) was demonstrated, oxygen transfer did not occur with the combinations investigated. In contrast to the failure of the above metalloenzymes to catalyse new reactions, papain modified at the active site sulfhydryl group by thiazolium salts and pyridinium salts was shown to exhibit reactions characteristic of the covalently attached cofactor. Thus the thiazolopapains acted as decarboxylation catalysts for pyruvate and the pyridinopapains could be reduced to dihydropyridines which reduced electrophilic carbonyl substrates with small enantiomeric excess.