Synthesis and application of enantioenriched functionalized α-tetrasubstituted α-amino acids from biocatalytic desymmetrization of prochiral α-aminomalonamides.
Catalyzed by Rhodococcus erythropolis AJ270, an amidase-containing microbial whole cell catalyst in neutral phosphate buffer at 30 °C, a number of prochiral α-substituted α-aminomalonamides underwent highly efficient and enantioselective hydrolytic desymmetrization to afford functionalized α-tetrasubstituted α-amino acids in 74-98% chemical yields and 94.0 to >99.5% ee. The presence of a free α-amino (NH(2)) substituent in the substrates was deemed important to ensure high biocatalytic efficiency and enantioselectivity. The synthetic application of biocatalytic desymmetrization was demonstrated by practical chemical transformations of (R)-2-amino-2-carbamoylpent-4-enoic acid to α-substituted serine analogues and a bioactive diamino alcohol derivative.
Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Li-Bin
LB
Zhang
Li-Bing
LB
Zhang
De-Xian
DX
Wang
Liang
L
Zhao
Mei-Xiang
MX
Wang
D000581:Amidohydrolases / Q000737:chemistry / Q000378:metabolism*; D000596:Amino Acids / Q000096:biosynthesis* / Q000737:chemistry; D055162:Biocatalysis; D006868:Hydrolysis; D008314:Malonates / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D012240:Rhodococcus / Q000201:enzymology*; D013237:Stereoisomerism
D000596:Amino Acids; D008314:Malonates; D000581:Amidohydrolases