Bioreduction of Nitroolefins

Nitroalkenes are excellent substrates for bioreduction, given the strong electron-withdrawing power of the nitro group. In addition, its unrivaled chemical versatility (nitroalkanes can be easily converted to amines, acids, oximes, nitriles, and so on) enables a wide range of useful synthons to be obtained from the saturated products. 

In contrast to the reduction of carbonyl-activated substrates (e.g., cydohexenone), which is known to be concerted, it has been demonstrated that in the reduction of nitrocyclohexene and other simple nitroolefins the hydride transfer and the proton transfer are separate steps, forming the nitronate ion as a freely dissociable intermediate [95,96]. 

Exploiting the bioreduction of a nitrochromene, another biocatalytic approach to the synthesis of the antidepressant robalzotan has been developed, though with modest enantioselectivity [103]. 

As already observed for the tetrasubstituted C=C double bonds of substituted cinnamaldehydes, the bioreduction of a,p-dimethyl nitrostyrenes was also shown to be efficient albeit poorly diastereoselective, in the case of both whole cells and with isolated ene reductases [53,100]. 

As an alternative approach to classical OYE-like ene reductases, also cell-free extracts of anaerobic bacteria such as Clostridium sporogenes were tested for the bioreduction of a library of nitroalkenes [106]. The iron-sulfur cluster dependent enoate reductases responsible for the C=C bioreduction in Clostridia showed the same stereopreference of OYEl-3 on ( )-81 and related nitroolefins. As with ene reductases, nonaromatic substrates were converted more slowly and a,P-disubstituted nitroalkenes yielded almost racemic products. The relatively low deuterium exchange rate at the a-position (employing a biphasic system) confirmed also in this case that the low optical purity of the products is mostly due to the bioreduction itself, rather than to chemical racemization. 

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