THE USE OF ENZYMES FOR THE PREPARATION OF BIOLOGICALLY-ACTIVE NATURAL-PRODUCTS AND ANALOGS IN OPTICALLY-ACTIVE FORM

The enantioselective hydrolysis of chiral esters using esterases and l ipases gives access to key optically active intermediates on route to prostaglandins, coriolic acid, the anti-HIV agent carbovir and mevinic acid type hypocholestemic agents. The hydrolysis of meso-esters using hydrolases is a very efficient strategy in organic synthesis and has been used to prepare the carbocyclic nucleosides neplanocin and ariste romycin. Acylases have been used to prepare (-)-carbovir and both enan tiomers of a GABA-mimetic from 2-azabicyclo[2.2.1]hept-5-en-3-one. The employment of nitrilases and nitrile hydratases is gaining in popular ity; for example, prochiral 2-benzoyloxypropane-1,3-dinitrile is hydro lysed to (S)-3-benzoyloxy-4-cyanobutanoic acid with exquisite selectiv ity. Lipases in organic solvents can effect esterification, transester ification and interesterification reactions and this popular methodolo gy has been used to prepare key norcarbocyclic nucleotides and carbocy clic oxetanocin A in single enantiomer form. Yeast-catalysed reduction s of ketones afford optically active secondary alcohols, typically emp loyed for the synthesis of pheromones, fragrances and chemotactic agen ts such as leukotriene-Bq. Instead of a whole-cell system such as yeas t, partially purified dehydrogenases can be employed to synthesise (S) -secondary alcohols, for example an intermediate to the antifungal age nt brefeldin-A. Biohydroxylations are important reactions and are bein g applied to a wide range of substrates. The oxidation of benzene and derivatives to the corresponding cyclohexadiene diets are classic exam ples and have provided a route to analogues of cyclophellitol. Similar ly, mono-oxygenase catalysed Baeyer-Villiger reactions are now well-do cumented and have furnished intermediates to carbocyclic-AZT, lipoic a cid and azadirachtin. Sulfoxides of high optical purity have been prep ared by yeast-catalysed oxidation, while enzymes in the transferase an d lyase classes have been used to make carbohydrates and amino acids. In conclusion, the science of biotransformations opens up numerous syn thetic routes to a wide variety of target molecules that are not easil y accessible by other methods of synthetic organic chemistry.