Nitrile biotransformations for highly enantioselective synthesis of oxiranecarboxamides with tertiary and quaternary stereocenters; efficient chemoenzymatic approaches to enantiopure alpha-methylated serine and isoserine derivatives.
[reaction: see text] Biotransformations of a number of differently substituted and configured oxiranecarbonitriles using Rhodococcus sp. AJ270, a microbial whole-cell catalyst that contains nitrile hydratase/amidase, were studied. While almost all trans-configured 3-aryl-2-methyloxiranecarbonitriles and 2,3-dimethyl-3-phenyloxiranecarbonitrile were efficiently hydrated by the action of the less enantioselective nitrile hydratase, the amidase exhibited excellent 2S,3R-enantioselectivity against 2-methyl-3-(para-substituted-phenyl)oxiranecarboxamides. Under very mild conditions, biotransformations of nitriles provided an efficient and practical synthesis of 2R,3S-(-)-3-aryl-2-methyloxiranecarboxamides, electrophilic epoxides with tertiary and quaternary stereocenters, in excellent yield with enantiomeric excess greater than 99.5%. The synthetic applications of the resulting enantiomerically pure epoxides were demonstrated by convenient and straightforward syntheses of polyfunctionalized chiral molecules possessing a quaternary stereocenter such as R-(+)-2-hydroxy-2-methyl-3-phenylpropionic acid, 2R,3R-(-)-3-amino-2-hydroxy-2-methyl-3-phenylpropionic acid, and 2S,3S-(+)-2-amino-3-hydroxy-2-methyl-3-phenylpropionic acid, employing the regio- and stereospecific epoxide ring opening reactions of 2R,3S-(-)-2-methyl-3-phenyloxiranecarboxamide as the key steps.
Wang
Mei-Xiang
MX
Laboratory for Chemical Biology, Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, People's Republic of China. mxwang@iccas.ac.cn
Deng
Gang
G
Wang
De-Xian
DX
Zheng
Qi-Yu
QY
D000577:Amides / Q000138:chemical synthesis*; D001711:Biotransformation; D009570:Nitriles / Q000493:pharmacokinetics*; D012240:Rhodococcus / Q000378:metabolism; D012694:Serine / Q000031:analogs & derivatives* / Q000737:chemistry*; D013237:Stereoisomerism
D000577:Amides; D009570:Nitriles; D012694:Serine; C072421:isoserine