Synthesis Of Oxygen-containing Heterocyclic Compounds Catalyzed By Immobilized Lipase

Oxygen-containing heterocyclic compounds are diverse in variety and large in number.They are widely found in nature.They have high physiological activity and application value.They are the heterocyclic bases for many drugs,agricultural products,and fine chemicals.With the rapid development of modern biotechnology and the continuous deepening of enzymology research,enzymes have become more and more widely used as biocatalysts.Lipases have gradually become It is an enzyme that is widely used in organic synthesis.After lipase is immobilized,its catalytic efficiency is greatly improved,and its tolerance to reaction medium and reaction temperature is also greatly improved,and the immobilized lipase can be reused.This thesis mainly studied the synthesis of 2H-chromene and polyhydroxyfuran by immobilized lipase through multi-component reaction and Cascade reaction.2H-chromene is a key structural unit in a variety of biologically active molecules.The derivatives of 2H-chromene have high medicinal value.This is the first time that magnetic multiwall carbon nanotube immobilized lipase has been applied to2H-chromene.Synthesis of chromene.Porcine pancreatic lipase(PPL)was immobilized on magnetic multi-walled carbon nanotubes,and substituted2H-chromene was successfully synthesized.The catalytic activity of immobilized PPL is higher than that of free PPL.This article explores the influence of reaction medium,temperature and enzyme dosage on the reaction yield.The optimal reaction conditions were obtained: salicylaldehyde(1 mmol),acetylacetone,(1 mmol)methanol,(10mmol)protein content(30 mg)DMF(5 ml)and reacted at 65℃ for 6 hours to obtain satisfactory yields of 2H-chromenes(78%-97%).The immobilized PPL exhibits good catalytic performance for the synthesis of substituted 2H-chromenes,and the immobilized PPL not only improves the stability but also can be separated easily due to its magnetic properties,and can be reused 5 times.As an important heterocyclic substrate for many natural compounds,polyhydroxyalkylfurans,especially medicines,chemicals,fine chemicals and agrochemicals,have always been chemically synthesized polyhydroxyalkylfurans.An enzymatic method was reported for the synthesis of polyhydroxyalkylfurans firstly.We investigated the influence of enzyme source,reaction medium,temperature,and enzyme dosage on the reaction yield.Under the optimal conditions(sugar(1 mmol),malononitrile(1 mmol),water(1 ml),Novozym 435(200 U,13.2 mg)),the product yield(79%-92%)can be obtained after 6 hours of reaction at the reaction temperature(60 °C),and no by-products are found in the system.Novozym 435 showed satisfactory chemical selectivity and good reusability in this reaction.This work explores the great potential of enzymatic synthesis of polyhydroxyalkylfurans and expands the application of enzymatic catalytic promiscuity in organic synthesis.