Nitrile biotransformation for highly enantioselective synthesis of 3-substituted 2,2-dimethylcyclopropanecarboxylic acids and amides.
Biotransformations of differently configured 2,2-dimethyl-3-substitued-cyclopropanecarbonitriles were studied using a nitrile hydratase/amidase-containing Rhodococcus sp. AJ270 whole-cell catalyst under very mild conditions. Although all of the cis-3-aryl-2,2-dimethylcyclopropanecarbonitriles appeared inert toward the biocatalyst, a number of racemic trans-isomers efficiently underwent a highly enantioselective hydrolysis to produce (+)-(1R,3R)-3-aryl-2,2-dimethylcyclopropanecarboxylic acids and (-)-(1S,3S)-3-aryl-2,2-dimethylcyclopropanecarboxamides in high yields with excellent enantiomeric excesses in most cases. The overall enantioselectivity of the biotransformations of nitriles originated from the combined effects of 1R-enantioselective nitrile hydratase and amidase, with the later being a dominant factor. The influence of the substrates on both reaction efficiency and enantioselectivity was discussed in terms of steric and electronic effects. Coupled with chemical transformations, biotransformations of nitriles provided convenient syntheses of optically pure geminally dimethyl-substituted cyclopropanecarboxylic acids and amides, including chrysanthemic acids, in both enantiomeric forms.
Wang
Mei-Xiang
MX
Laboratory of Chemical Biology, Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, China. mxwang@infoc3.icas.ac.cn
Feng
Guo-Qiang
GQ
D000577:Amides / Q000138:chemical synthesis*; D000581:Amidohydrolases / Q000378:metabolism*; D001711:Biotransformation; D003521:Cyclopropanes / Q000138:chemical synthesis*; D006836:Hydro-Lyases / Q000378:metabolism*; D006868:Hydrolysis; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry / Q000378:metabolism*; D012240:Rhodococcus / Q000201:enzymology*; D013237:Stereoisomerism; D013379:Substrate Specificity
D000577:Amides; D003521:Cyclopropanes; D009570:Nitriles; C015766:cyclopropanecarboxylic acid; D000581:Amidohydrolases; C019665:amidase; D006836:Hydro-Lyases; C048831:nitrile hydratase