The Research On The Stereo-and Regio-selective Oxidation Of Aromatic Sec-amines With Biocatalysts

Objective: To screen an efficient biocatalyst which can selectively activate C-H bond and to make the functionalization of C-H bond in the presence of sec-amino group,which will enrich the synthetic methodology.Methods: 1,2,3,4-tetrahydroquinoline was used as model substrate to screen the biocatalyst in whole cells.Then to establish the reaction system through optimization of reaction conditions and to make clear relationship between the structure of substrate and biocatalysts,Furthermore,reaction mechanism and characterization of enzyme will be investigated.Results:(1)(R)-1,2,3,4-tetrahydroquinolin-4-ol and(R)-2,3,4,5-tetrahydro-1H-benzo[b]a zepin-5-ol with 99% ee value and good yields were obtained by site-selective oxidation of C-H and N-H bonds in the catalysis of Pseudomonas sp.ZMU-T02 and Pseudomonas sp.ZMU-T06 whole cells;(2)A series of lactams were obtained with the selective oxidation at α-position of tetrahydroquinoline derivitives with mutant of Pseudomonas sp.ZMU-T04 induced by p-xylene in 8%-84% yields.Besides,N-phenylformamides were obtained in 13%-55% yield with the catalysis of ZMU-T04 whole cell;(3)An initial study on the enzyme characterization of Pseudomonas sp.ZMU-T04 showed NADH cofactor is prefered with the catalysis of supernate after the cell distuption with ultrasonication.Conclusion: A green method was built to synthesize chiral 1,2,3,4-tetrahydro quinolin-4-ol and(R)-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-ol through the directed asymmetric hydroxylation of C-H at benzyl position with a novel biocatalyst containing highly stereo-and regio-selective monooxgenase.In addition,a method to synthesize amides with the catalysis of Pseudomonas sp.ZMU-T04 mutant was established,which is a new attempt on biocatalysis in the field of organic synthesis and will make a great contribution to the development of biocatalysis.