Nitrile biotransformations for the efficient synthesis of highly enantiopure 1-arylaziridine-2-carboxylic acid derivatives and their stereoselective ring-opening reactions.
Catalyzed by the Rhodococcus erythropolis AJ270 whole cell catalyst under very mild conditions, biotransformations of racemic 1-arylaziridine-2-carbonitriles proceeded efficiently and enantioselectively to produce highly enantiopure S-1-arylaziridine-2-carboxamides and R-1-arylaziridine-2-carboxylic acids in excellent yields. Although the nitrile hydratase exhibits no selectivity against all nitrile substrates, the amidase is highly R-enantioselective towards 1-arylaziridine-2-carboxamides. When treated with benzyl bromide, 1-phenylaziridine-2S-carboxamide underwent a highly regioselective and enantiospecific ring-opening reaction to afford an almost quantitative yield of R-beta-[(benzyl)phenylamino]-alpha-bromopropanamide (C-2 attack) and R-alpha-[(benzyl)phenylamino]-beta-bromopropanamide (C-3 attack) in a 10.5:1 ratio. Further treatment of the resulting ring-opening products with an N-nucleophilic reagent such as amine and azide led to, through most probably the aziridinium intermediate, the formation of S-alpha-substituted-beta-[(benzyl)phenylamino]propanamides in good chemical yields with high enantiomeric purity.
Wang
Jin-Yuan
JY
Beijing National Laboratory for Molecular Sciences, Laboratory of Chemical Biology, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, China.
Wang
De-Xian
DX
Zheng
Qi-Yu
QY
Huang
Zhi-Tang
ZT
Wang
Mei-Xiang
MX
D001388:Aziridines / Q000138:chemical synthesis*; D001711:Biotransformation; D002264:Carboxylic Acids / Q000138:chemical synthesis; D006836:Hydro-Lyases / Q000378:metabolism; D009570:Nitriles / Q000378:metabolism*; D012240:Rhodococcus / Q000378:metabolism*; D013237:Stereoisomerism
D001388:Aziridines; D002264:Carboxylic Acids; D009570:Nitriles; C033132:aziridine; D006836:Hydro-Lyases; C048831:nitrile hydratase