The Synthesis And Bioactivity Of Organic Small Molecules Such As Aromatic Rings Catalyzed By Azacarbene And Organic Bases

As a kind of very important organic small molecule catalyst,N-heterocyclic carbine(NHC)provides a variety of methods for its efficient construction of carbon-carbon bonds with its unique polarity reversing properties.This thesis contains two parts:The first part: mainly describes the background of N-heterocyclic carbene catalysis in recent years,Five typical catalytic modes are described in this chapter based on the different reaction intermediates:(1)enolate intermediates(α-carbonyl);(2)Homoenolate intermediate(β-carbonyl);(3)acyl anion intermidiate(carbon carbonyl);(4)α,β-unsaturated acyl oxazole intermediate;(5)γ-carbon anion.The second part conclusions are shown as follows:1 N-heterocyclic carbenes(NHCs)have been intensively studied and applied by scientists as efficient ligand in transition metal catalysis.Due to their strong electron-donating features,they could also react as powerful nucleophilic organocatalysts in a variety of chemical transfermations.Although the application of NHC as organocatalyst could be found early in the 1940 s,it was not until the last decade did NHC organocatalysis experience an explosive development with numerous novel activation modes and exceptical chemo-and stereo-selectivities,After that,N-heterocyclic carbenes have been proved to be powerful organocatalysts in asymmetric reactions.This chapter mainly describes N-heterocyclic carbine(NHC)catalyzed cross-aza-benzoin reaction of α,β-unsaturated aldehydes with isatin derived imine substrates.Products of 3-aminoindole compounds bearing a chiral quaternary carbon center could be obtained in good chemical and stereoselectivities(ee: ~ 96% yield: 76%).2 The simple method of constructing benzene ring by using coumarins and aldehydes under the catalysis of alkali is described.3,4-Benzocoumarin is a kind of unique scaffold widely found in natural products such as anesthetics and some interesting bioactive molecules.The synthesis of these compounds has received considerable attention.There are few studies on the construction of benzene ring,Therefore,we report that a series of 3-acetylcurcine can be used to stimulate the tandem reaction in the absence of a catalyst,an ordinary base and a conventional solvent at room temperature to obtain good yields(51-85%).3 An N-heterocyclic carbene(NHC)catalyzed domino reaction triggered by a δ-LUMO activation of α,β-γ,δ-diunsaturated enal has been developed for the formal [4+2] construction of multisubstituted arenes and 3-ylidenephthalide.These two products,formed in a highly chemo-and regioselective manner,were obtained via different catalytic pathways due to a simple change of the substrate.The activation of the remote δ-carbon of unsaturated aldehydes expands the synthetic potentials of NHC organocatalysis.4 In this chapter,the muti-substituted pyridine compounds were prepared by the addition of α-β-unsaturated acylpyrazole intermediates and imines in the azole ring formation through carbene catalyzed by the [3 + 2] cycloaddition reaction.The antiviral activity of most of the target compounds was screened by TMV as the test object.The results showed that some of the target compounds had good anti-TMV activity,among which the therapeutic activities of compounds III3,III10 and III12 were 53%,60% and 59%,respectively,higher than that of Ningnanmycin(49%).The target compounds were subjected to E.verticillicum,P.infestans,T.cucumeris by using the growth rate method(using potato dextrose agar medium(PDA)B.cinerea,G.zeae,S.sclerotiorum,F.oxysporum,C.mandshurica,apple anthrax(C)The results showed that the target compound had no obvious inhibitory effect on the fungi,but it had the effect of promoting the growth of some fungi.Although the target compound had no effect on the fungi,But in the future design and synthesis of potentially highly active compounds to provide guidance.