Nitroalkene

Nitroalkene

Ene-Reductases in Pharmaceutical Chemistry

Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019

Chiral nitroalkanes (entry 2) are used as precursors for drugs such as Tamsulosin, an alpha blocker sold under the tradename Flomax®, and Selegiline, a monoaminooxidase B inhibitor used to treat Parkinson’s disease and depression. A highly enantioselective chemoenzymatic process toward these building blocks was developed by coupling the in situ synthesis of α-methylated nitroalkene with its subsequent asymmetric reduction via a recombinant ene-reductase from Gluconobacter oxydans (99% conversion and >90% ee) (Burda et al., 2013).

Asymmetric organocatalysis in drug discovery and development for active pharmaceutical ingredients

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Journal Information

Published in Expert Opinion on Drug Discovery, 2023

Anthony J. Burke

In 2015, Bae and Song described the synthesis of this target using a cinchona-squaramide catalyst 17 (Figure 2, D) [41]. This was an excellent piece of work as the reaction was performed at the multi-gram scale in brine using the nitroalkene 16 and dimethyl malonate 18 at 0°C to afford the Michael adduct 19 (not isolated) with >95% conversion and 91% ee, which was converted to a lactam via a Raney Nickel hydrogenation of the nitro group followed by cyclization and hydrolysis of the lactam to the (S)-pregabalin target (95% yield and 91% ee).

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Ene-Reductases in Pharmaceutical Chemistry

Asymmetric organocatalysis in drug discovery and development for active pharmaceutical ingredients