The Research Of Biocatalytic Promiscuity With One-pot Synthesis Of Pyridine And Chromene Derivatives

One pot synthesis of1,4-DHPs, pyrazolo [3,4-b] pyridines and2-amino-4H-chromenes catalyzed by enzyme was researched. The reseach not only extends the application of enzymes in pharmaceutical industry but also gives new evidences for biocatalytic promiscuity.Part1:One pot synthesis of1,4-DHPs catalyzed by Lipase. We screened12commercial enzymes to catalyse four-component reaction to form1,4-DHPs. And we found that Lipase from Porcine pancreas displayed observable activities for the synthesis of1,4-DHPs. After investigating enzyme sources, solvents, reaction temprature, enzyme concentration and the effect of structure of substrate, and291,4-DHPs were prepared and we proposed a mechanism for the reaction.Part2:One-pot synthesis of2-amino-4H-chromene catalyzed by Lipase or Amlyse. We screened enzymes to catalyze the reaction of aromatic or aliphatic aldehydes、1,3-dicarbonyl compounds and malononitrile or cyanoacetic ester, and we found that lipase from porcine pancreas or α-amylase from hog pancreas showed the highest catalytic activity of hantzch reaction.32hantzch products were synthesised and The mechanism of the reaction catalyzed by lipase was proposed.Part3:One-pot synthesis of pyrazolo [3,4-b] pyridines catalyzed by Trpsin or Lipase. we found that PPL or PPT showed excellent catalytic activity in the synthesis of pyrazolo[3,4-b]pyridine derivatives. At the condition of4≤pH≤6, it has good adaptability to different substrates in this reaction. This kind of lipase catalytic reaction provides a new method for synthetic pyrazolo [3,4-b] pyridine derivatives and expanded the enzyme application in organic synthesis.74compounds wre synthesised, and the products were characterized by IR, EI-MS、1H-NMR、13C-NMR、HRMS-ESI.