Highly efficient and enantioselective biotransformations of racemic azetidine-2-carbonitriles and their synthetic applications.
Catalyzed by the Rhodococcus erythropolis AJ270 whole cell catalyst in neutral aqueous buffer at 30 degrees C, a number of racemic 1-benzylazetidine-2-carbonitriles, trans-1-benzyl-4-methylazetidine-2-carbonitrile, and 1-benzyl-2-methylazetidine-2-carbonitrile and their amide substrates underwent efficient and enantioselective biotransformations to afford the corresponding azetidine-2-carboxylic acids and their amide derivatives in excellent yields with ee up to >99.5%. The overall excellent enantioselectivity of the biocatalytic reactions stemmed from a combined effect of a very active but virtually nonenantioselective nitrile hydratase and a high R-enantioselective amidase involved in microbial whole cells. The synthetic applications have been demonstrated by the nucleophilic ring-opening reactions of azetidiniums of the resulting chiral azetidine-2-carbox amide derivatives for the preparation of alpha,gamma-diamino, alpha-phenoxy-gamma-amino, and alpha-cyano-gamma-amino carboxamides. The intramolecular CuI-catalyzed cross-coupling reaction for the synthesis of azetidine-fused 1,4-benzodiazepin-2-one derivative was also presented.
Leng
Dong-Hui
DH
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Wang
De-Xiang
DX
Pan
Jie
J
Huang
Zhi-Tang
ZT
Wang
Mei-Xiang
MX
D000577:Amides / Q000737:chemistry / Q000378:metabolism; D001383:Azetidinecarboxylic Acid / Q000737:chemistry / Q000378:metabolism; D001384:Azetidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D001711:Biotransformation; D007700:Kinetics; D012240:Rhodococcus / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity
D000577:Amides; D001384:Azetidines; D001383:Azetidinecarboxylic Acid