Nitrilase‐Catalyzed Enantioselective Synthesis of Pyrrolidine‐ and Piperidinecarboxylic Acids

Abstract

The enantioselective synthesis of the nonproteinogenic amino acids b-proline and nipecotic acids from their readily available nitriles is achieved in high enantiomeric excess by commercially available nitrilases. The presented procedure comprises not more than 4 steps, thus considerably reducing the multiple steps generally required. Amide formation is also observed for specific heterocyclic nitriles.

Current applications of kinetic resolution in the asymmetric synthesis of substituted pyrrolidines

“…In 2007, Klempier et al employed nitrilase NIT-106 in the synthesis of β-amino acid 30 (Scheme 7). 34 Nitrilase catalysed hydrolysis of racemic 3-nitrile-pyrroline (±)-29 afforded the βamino acid 30 in a good 42% yield at 44% conversion with a good enantioselectivity of 76% ee. Higher conversions at longer reaction times afforded the amide by-product 31.…”

Expanding the organic toolbox: a guide to integrating biocatalysis in synthesis

“…In this process formaldehyde is reacted with hydrogen cyanide to produce glycolonitrile, which is directly converted to the desired glycolic acid by a nitrilase that was immobilized under conditions allowing for retention of enzyme activity upon recycling. 72 In order to explore the synthetic utility of commercially available nitrilases, Winkler et al screened the nitrilases NIT-101 through NIT-108 from Biocatalytics, for selective hydrolysis of a series of heterocyclic amino nitriles to their corresponding carboxylic acids 73 (Scheme 9). The most active and selective nitrilases identified were applied to demonstrate the chemoenzymatic enantioselective synthesis of cis-and trans-configured five-and sixmembered ring carbocyclic g-amino acids in good yields.…”

Synthesis of Nitriles from Aldoximes and Primary Amides Using XtalFluor-E

“…A 0.2 M solution of the corresponding methyl ester in aq NH 4 OH (28-30%) was stirred at r.t. for 16 h. The solvent was evaporated to afford the amide, which was, in some cases, purified by silica gel chromatog-raphy. The known amides 3, 33 5a, 34 5b, 6c 5h, 35 11a, 36 11b, 37 11c, 36 11e, 38 11h, 4 11i, 39 11j, 39 13, 40 14, 41 20, 42 and 23 43 were synthesized following the general procedure described above. Compound 5e was synthesized following the literature.…”