Stereoselective Synthesis of Drugs and Drug Precursors by Hydrolases and Oxidoreductases

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Abstract
Several hydrolases have been employed for the resolution, carried out both in aqueous and organic media, of compounds of pharmaceutical interest. Among these are the mucolytic drug trans-sobrerol, the precursors of (R)- and (S)-broxaterol (a β-adrenergic stimulant), of (R)- and (S)-cycloserine and of (+)- and (-)-desoxymuscarine, and several 2-cyclohexen-l-ols (building blocks for the synthesis of eburnane alkaloids) and bicyclic isoxazolines (building blocks for aminosugars, antibiotics and β-hydroxyacids). The regioselective acylation of chloramphenicol and bile acids has also been achieved by lipases. Hydroxysteroid dehydrogenases have been used to carry out the selective oxidoreduction of both steroidic and non-steroidic compounds. For example, precursors of chenodeoxycholic acid and ursodeoxycholic acid, drugs widely employed for the dissolution of cholesterol gall stones, have been prepared in high yield and purity in membrane reactors with NAD(P)(H) regeneration. The precursors of the eight stereoisomers of muscarine have also been prepared with the same enzymes.