Abstract:
The present invention relates to β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloid derivatives (I) and a method for preparing same and the use in the aspects of preventing and treating plant viruses, fungicides and insecticides. For the meaning of each group in formula (I) see the description. The β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloid derivatives of the present invention show a particularly ourstanding anti-plant virus activity, and also have fungicidal and insecticidal activities.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims priority to Chinese Application No. 201310752240.2, filed on Dec. 30, 2013, entitled “β-Carboline, Dihydro-β-Carboline and Tetrahydro-β-Carboline Alkaloid Derivatives and Preparation Methods Same and Use in Aspects of Preventing and Treating Plant Viruses, Fungicides and Insecticides”, which is specifically and entirely incorporated by reference. 
       FIELD OF THE INVENTION 
       [0002]    The present invention relates to β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloid derivatives and their preparation methods and use in the preventing and treating plant viruses fungicides and insecticides and pertains to the technical field of pesticides. 
       BACKGROUND OF THE INVENTION 
       [0003]    The skeleton structures of β-carboline, dihydro-β-carboline and tetrahydro-β-carboline widely exist in natural products and drug molecules. Harmine and tetrahydroharmine belong to β-carboline and tetrahydro-β-carboline alkaloids respectively and are representative compounds of harmala alkaloids. Harmine was first separated from  P. harmala  L. This alkaloid shows cytotoxicity to leukemia cell lines HL60 and K562. Tetrahydroharmine is a fluorescent molecule separated from Malpighiacease plant  Banisteriopsis caapi . This compound has weak inhibition to the re-uptake of 5-hydroxytryptamine. Harmaline is an agonist of the central nervous system and a reversible inhibitor of monoamine oxidase (MAO-A). 
         [0000]    
       
                 
         
             
             
         
       
     
         [0004]    Currently, the research on β-carboline, dihydro-β-carboline and tetrahydro-β-carboline and substances similar to them focuses on anti-tumor, killing of human parasites and monoamine oxidase inhibitors. However, as far as we know, no document reports the activity of β-carboline, dihydro-β-carboline and tetrahydro-β-carboline and substances similar to them against plant viruses, and little was reported on their bactericidal activity and insecticidal activity. In the aspect of bactericidal activity: Fu Haibo et al from Gansu Agricultural University researched and found in 2007 that the extracting solutions of  P. harmala  L. in different solvents all have certain inhibiting effect to spore germination of four kinds of pathogenic bacteria, including  Botrytis cinerea, Fusarium oxysporum, Alternaria solani  and  Cladosporium cucumerinum  Ellis et Arthur, and their EC 50  is 0.060, 0.199, 0.105 and 0.223 g/mL respectively (Fu Haibo, Ding Defang, Zhao Hongmei, Yang Shunyi, Grassland and Lawn, 2008, 1, 44-48); in 2007, Wen Ren et al from Fudan University reported derivatives with a structure of 1-(3-indol)-1,2,3,4-tetrahydro-β-carboline and researched the in vitro activity of these derivatives against  Pyricularia oryzae  (CN101020688); in 2011, Zhang Yaomou et al from South China Agricultural University reported compounds with a structure of β-carboline-3-oxime ester and meanwhile studied the inhibitory activity of these compounds against  Colletotrichum musae, Colletotrichum gloeosporioides  and tomato late plight (Lu Shaoying, Zhang Yaomou, Synthetic Chemistry, 2011, 19 (6), 769-772); in 2012, this research group again reported compounds with a structure of 1-p-trifluoromethylphenyl-β-carboline-3-carbonyl bishydrazide, but the quantity of the compounds was small and their bacteriostatic activity against Rhizoctorzia  solani  was tested only (Cai Ying, Huang Jianfeng, Zhang Meidan, Zeng Yong, Zhang Yaomo, Synthetic Chemistry, 2012, 20(6), 736-739.). In the aspect of insecticidal activity: in 2005, Zhao Xiaomeng et al from Beijing University of Agriculture reported the contact activity of the ethanol extract, chloroform extract and water extract of the overground part of  P. harmala  L. in the growing period against  Myzus persicae, Macrosiphum rosivorum  and  Tetranychus cinnabarinus . The result is that their contact activity against spider mites is all above 95% at concentration of 10 mg/mL, and that against two kinds of aphids is above 70% at concentration of 10 mg/mL (Zhao Xiaomeng, Zeng Zhaohai, Chinese Agricultural Science Bulletin, 2005, 21(4), 278-279); in 2010, Zhong Guohua et al from South China Agricultural University reported the insecticidal activity of 1,3-disubstituted β-carboline and tetrahydro-β-carboline derivatives against  culex pipiens  larvae and  Lipaphis erysimi . To be specific, the LC 50  of the compounds with a structure of 1-phenyl substituted β-carboline and tetrahydro-β-carboline-3-methyl ester against  culex pipiens  larvae is 20.82 mg/L and 23.98 mg/L respectively, and the LC 50  against  Lipaphis erysimi  is 53.16 mg/L and 68.05 mg/L respectively (Zeng, Y; Zhang, Y M.; Weng, Q. F.; Hu, M. Y.; Zhong G H.  Molecules  2010, 15, 7775-7791). 
       SUMMARY OF THE INVENTION 
       [0005]    The object of the present invention is to provide β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloid derivatives and their preparation methods and use in the preventing and treating plant viruses and killing of bacteria and insects. The β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloid derivatives described in the present invention show very good activity against plant viruses and also show bactericidal activity and insecticidal activity. The β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloid derivatives described in the present invention are compounds with a structure shown in the following general formula (I): 
         [0000]    
       
                 
         
             
             
         
       
     
         [0006]    The β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloid derivatives (I) described in the present invention are compounds with structures shown in the following four general formulas (I a , I b , I c , I d ): 
         [0000]    
       
                 
         
             
             
         
       
     
         [0007]    The β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloid derivatives (I) described in the present invention further comprise natural compounds with structures shown in the following formulae: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0008]    The dihydro-β-carboline alkaloid described in the present invention may be prepared by the following method (Path 1): firstly introducing aldehyde group to indol 3-site to obtain compound 1, the compound 1 then reacts with nitromethane and ammonium acetate to obtain intermediate 2, the intermediate 2 is reduced to obtain tryptamine 3, and then the tryptamine 3 is acylated and cyclized to obtain dihydro-β-carboline alkaloid harmalan. 
         [0009]    Path 1: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0010]    The β-carboline and tetrahydro-β-carboline alkaloid described in the present invention may be prepared by the following method (Path 2): firstly, reacting tryptamine 3 with an acetaldehyde aqueous solution under the catalysis of sulfuric acid to obtain tetrahydro-β-carboline alkaloid tetrahydroharmane, which is then further dehydrogenated by one step and oxidized to obtain β-carboline alkaloid harmane. 
         [0011]    Path 2: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0012]    The tetrahydro-β-carboline alkaloid described in the present invention may be prepared by the following method (Path 3): firstly, reacting harmine with benzyl bromide to obtain quaternary ammonium salt 4, which is then reduced to obtain compound 5; lastly, the compound 5 is hydrogenated under the catalysis of Pd/C to obtain tetrahydro-β-carboline alkaloid tetrahydroharmine. 
         [0013]    Path 3: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0014]    The β-carboline alkaloid described in the present invention may be prepared by the following method (Path 4): Harmine is demethylated under acidic condition to obtain β-carboline alkaloid harmol. 
         [0015]    Path 4: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0016]    The β-carboline alkaloid derivatives (I a ) described in the present invention may be prepared by the following method (Path 5): reacting Harmane with bromosuccinimide under acidic condition to obtain compounds I a -1 and I a -2, and reacting the obtained compounds with sodium nitrate under acidic condition to obtain compounds I a -3 and I a -4 containing substituted nitro on phenyl ring. 
         [0017]    Path 5: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0018]    The β-carboline alkaloid derivatives (I) described in the present invention may be prepared by the following method (Path 6): reacting Harmol with isocyanate to obtain compound I a -5, reacting Harmol with acyl chloride to obtain compound I a -6-I a -8, and reacting Harmol with amino acid in presence of a condensation agent to obtain compound I a -9. 
         [0019]    Path 6: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0020]    The β-carboline and tetrahydro-β-carboline alkaloid derivatives (I a  and I b ) described in the present invention may be prepared by the following method (Path 7): firstly, reacting L-tryptophan with an acetaldehyde aqueous solution to obtain cyclization product I b -1, which is then further esterified by one step to obtain compound I b -13. Compound I b -13 is dehydrogenated and oxidized to obtain compound I a -10. Compound I a -10 is hydrolyzed under alkaline condition to obtain compound I a -11. Compound I a -10 is reduced by lithium aluminum hydride to obtain compound I a -12. The compound is oxidized to obtain aldehyde I a 13. Compound I a 13 reacts with malonic acid to obtain acrylic acid I a -14. By a same path, compound I a -15-I a -16 can be synthesized. 
         [0021]    Path 7: 
         [0000]    
       
                 
         
             
             
         
       
       
                 
         
             
             
         
       
     
         [0022]    The tetrahydro-β-carboline alkaloid derivatives (I b ) described in the present invention may be prepared by the following method (Path 8): L/D-tryptophan takes Pictet-spengler reaction with fatty aldehyde or aromatic aldehyde under acidic or alkaline condition to obtain acids I b -1-I b -6, and acids I b -1-I b -6 are further esterified to obtain ester I b -7-I b -12. 
         [0023]    Path 8: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0024]    The dihydro-β-carboline alkaloid derivatives (I b ) described in the present invention may be prepared by the following method (Path 9): reacting L-tryptophan with ethanol to obtain ethyl ester 6, which is acylated and then reacting with phosphorus oxychloride to obtain dihydro-β-carboline alkaloid derivative I b -14. 
         [0025]    Path 9: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0026]    The tetrahydro-β-carboline alkaloid derivatives (I b ) described in the present invention may be prepared by the following method (Path 10): reacting methyl ester I b -7 with hydrazine hydrate (80%) to obtain compound I b -15, and reacting compound I b -7 with amine to obtain amides I b -16 and I b -18. 
         [0027]    Path 10: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0028]    The tetrahydro-β-carboline alkaloid derivatives (I b ) described in the present invention may be prepared by the following method (Path 11): reacting acid I b -1 with amine in presence of a condensation agent to obtain amides I b -17, I b -19-I b -20. 
         [0029]    Path 11: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0030]    The tetrahydro-β-carboline alkaloid derivatives (I c ) described in the present invention may be prepared by the following method (Path 12): reacting hydrazide compound I b -15 with fatty aldehyde or aromatic aldehyde to obtain corresponding acylhydrazone type compound I c -1-I c -29. 
         [0031]    Path 12: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0032]    The tetrahydro-β-carboline alkaloid derivatives (I d ) described in the present invention may be prepared by the following method (Path 13): reacting hydrazide compound I b -15 with acyl chloride to obtain corresponding bishydrazide type compound 
         [0033]    Path 13: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0034]    In the above general formulas, 
         [0035]    R represents hydrogen, 1˜4 halogen atoms, 1˜4 nitro groups, 1˜4 cyano groups, 1˜4 C1-C6 alkoxy groups, 1˜4 hydroxy groups, 1˜4 ester groups, 1˜2OCH 2 O, 1-2OCH 2 CH 2 O, 1˜4 C0-C10 amino groups, 1˜4 C1-C6 alkyl carbonyl groups, 1˜4 C1-C10 alkoxy carbonyl groups, 1˜4 C1-C10 alkyl amino carbonyl groups, 1˜4 C1-C6 alkoxy carbonyloxy groups, 1˜4 C1-C6 alkyl amino carbonyloxy groups, 1˜4 C1-C10 α-amino alkyl carbonyloxy groups: 
         [0036]    R 1  respectively represents hydrogen, hydroxy, halogen atom, cyano group, ester group, amido group, C1-C10 hydrocarbyl, C1-C6 alkoxy, C1-C4 alkyl carbonyloxy, C1-C4 alkoxy carbonyloxy, C1-C10 nitrogen-containing heterocyclic ring, C1-C10 oxygen-containing heterocyclic ring, C1-C10 sulfur-containing heterocyclic ring, as well as stereomers of the foregoing compounds; 
         [0037]    R 2  respectively represents hydrogen, hydroxy, C1-C6 alkoxy, amino, C1-C10 amino, halogen atom, cyano group, aldehyde group, C1-C6 alkyl carbonyl, C1-C10 alkoxy carbonyl, C1-C10 alkyl amino carbonyl, C1-C6 alkoxy carbonyloxy, C1-C6 alkyl amino carbonyloxy; 
         [0038]    X respectively represents hydrogen, oxygen, sulfur, nitrogen, carbon; 
         [0039]    R 3  respectively represents hydrogen, hydroxy, halogen atom, cyano group, ester group, amido group, C1-C10 hydrocarbyl, C1-C6 alkoxy, C1-C4 alkyl carbonyloxy, C1-C4 alkoxy carbonyloxy, C1-C10 nitrogen-containing heterocyclic ring, C1-C10 oxygen-containing heterocyclic ring, C1-C10 sulfur-containing heterocyclic ring; 
         [0040]    R 4  and R 5  respectively represents hydrogen, C1-C10 hydrocarbyl, C1-C10 nitrogen-containing heterocyclic ring, C1-C10 oxygen-containing heterocyclic ring, C1-C10 sulfur-containing heterocyclic ring; R 4  and R 5  are C1-C10 aliphatic ring, C1-C10 unsaturated carbon ring, C1-C10 nitrogen-containing heterocyclic ring, C1-C10 oxygen-containing heterocyclic ring, C1-10 sulfur-containing heterocyclic ring; 
         [0041]    R 6  respectively represents hydrogen, hydroxy, amino, C1-C10 hydrocarbyl, C1-C6 alkoxy, C1-C10 amino group, substituted phenyl ring, C1-C10 nitrogen-containing heterocyclic ring, C1-C10 oxygen-containing heterocyclic ring, C1-C10 sulfur-containing heterocyclic ring. 
         [0042]    The β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloid derivatives (I) described in the present invention are preferably the following compounds:
   (E)-3-(1-methyl-pyridino[3,4-b]indol-3)-acrylic acid (I a -14);   (E)-3-(1-(thiophene-2)-pyridino[3,4-b]indol-3)-acrylic acid (I a -15);   (E)-3-(1-(pyridine-3)-pyridino[3,4-b]indol-3)-acrylic acid (I a -16);   (1S,3S)—N-butyl-1-methyl-2,3,4,9-tetrahydro-pyridino[3,4-b]indol-3-formamide (I b -16);   (1S,3S)—N-cyclohexyl-1-methyl-2,3,4,9-tetrahydro-pyridino[3,4-b]indol-3-formamide (I b -17);   (1S,3S)—N-(2-ethoxyl)-1-methyl-2,3,4,9-tetrahydro-pyridino[3,4-b]indol-3-formamide (I b -18);   (1S,3S)—N-(dimethyl amino methyl)-1-methyl-2,3,4,9-tetrahydro-pyridino[3,4-b]indol-3-formamide (I b -19);   (1S,3S)—N-((tetrahydrofuran-2)-methyl)-1-methyl-2,3,4,9-tetrahydro-pyridino[3,4-b]indol-3-formamide (I b -20);   (1S,3S)—N′-benzylidene-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine   (1S,3S)—N′-(4-tert-butyl benzylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -2);   (1S,3S)—N′-(4-dimethyl amino benzylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -3);   (1S,3S)—N′-(4-nitrobenzylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -4);   (1S,3S)—N′-(4-chlorobenzylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -5);   (1S,3S)—N′-(2,4-dichlorobenzylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -6);   (1S,3S)—N′-(4-dichlorobenzylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -7);   (1S,3S)—N′-(4-methoxybenzylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -8);   (1S,3S)—N′-methoxybenzylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -9);   (1S,3S)—N′-(2-methoxybenzylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -10);   (1S,3S)—N′-(3,4-dimethoxybenzylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -11);   (1S,3S)—N′-((benzo[d][1,3]dioxymethylene-5)-methylene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -12);   (1S,3S)—N-((2, 3-dihydrobenzo[b][1, 4]dioxin-6-methylene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -13);   (1S,3S)—N′-(6-hydroxynaphthalene-2-methylene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -14);   (1S,3S)—N′-(pyridine-4-methylene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -15);   (1S,3S)—N′-(pyridine-3-methylene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -16);   (1S,3S)—N′-(pyridine-2-methylene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -17);   (1S,3S)—N′-(furan-2-methylene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -18);   (1S,3S)—N′-(pyrrole-2-methylene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -19);   (1S,3S)—N′-(thiophene-2-methylene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -20);   (1S,3S)—N-(imidazole-2-methylene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -21);   (1S,3S)—N-((E)-but-2-enylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -22);   (1S,3S)—N′-butylidene-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -23);   (1S,3S)—N′-octadien-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -24);   (1S,3S)—N′-cyclohexylmethylene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -25);   (1S,3S)—N-(2,2-dimethylpropylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -26);   (1S,3S)—N(1-phenylethylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -27);   (1S,3S)—N′-(3-dimethyl-2-butylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -28);   (1S,3S)—N′-cyclohexylidene-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -29);   N′—((1S,3S)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-tricarboxylate)benzo[d][1,2,3]thiadiazole-7-formylhydrazine (I d -1);   4-methyl-N′-((1S,3S)methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-triformyl)-1,2,3-thiadiazole-5-formylhydrazine (I d -2);   (1S,3S)—N′-isonicotinoyl-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I d -3);   (1S,3S)—N′-benzoyl-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I d -4);   (1S,3S)—N′—N-hexanoyl-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I d -5);   (1S,3S)—N′-tert-valeryl-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I d -6);   (1S,3S)—N′-(cyclopentylformyl)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I d -7).   
 
         [0087]    The compounds shown in general formula (I) of the present invention have excellent activity against plant viruses, can satisfactorily inhibit tobacco mosaic virus, chilli virus, rice virus, tomato virus, sweet potato virus, potato virus and cucurbits virus and maize dwarf mosaic virus, may effectively prevent and control virus diseases of tobacco, chilli, paddy, tomato, cucurbitaceous vegetable, grain, vegetable, bean and other crops, and is particularly applicable to the prevention and treating of tobacco mosaic. β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloid derivatives shown in general formula (I) have very high in vitro activity against TMV and also show very good in vivo activity against tobacco mosaic virus (TMV), and the in vivo activity of some of β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloid derivatives against tobacco mosaic virus is obviously better than that of commercial variety virazole. Particularly, the activity of compounds Harmalan, Tetrahydroharmane, Harmane, Tetrahydroharmine, I a -1, I b -13, I b -15, I c -1-I c -9, I c -12, I c -19, I c -20, I c -24-I c -26, I c -28, I d -1, I d -6 and I d -7 against tobacco mosaic virus at concentration of 100 μg/mL is equivalent to the activity of commercial variety ningnanmycin at concentration of 100 μg/mL. As far as we know, it is also the first time to report β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloid and their derivatives have activity against plant viruses. 
         [0088]    The compounds shown in general formula (I) of the present invention can be used as inhibitors of plant viruses directly, or used by adding an agriculturally acceptable vector, or used by forming interactive compositions with other agents against plant viruses, such as: diazosulfide (BTH), tiadinil (TDL), 4-methyl-1,2,3-thiadiazole-5-formic acid (TDLA), DL-p-aminobutyric acid (BABA), virazole, ningnanmycin, phenanthroindolizidine alkaloid Antofine, linked triazole compounds XY-13 and XY-30, virus A, salicylic acid, polyhydroxy dinaphthaldehyde and amino oligosaccharin. Some of these compositions show a synergistic effect and some show an additive effect. 
         [0089]    The compounds shown in general formula (I) of the present invention have the activity of killing armyworms, cotton bollworms and corn borers as well as  culex pipiens.    
         [0090]    The compounds shown in general formula (I) of the present invention show bactericidal activity against the following 14 kinds of pathogenic bacteria: cucumber  fusarium  wilt,  Cercospora arachidicola, Macrophoma kawatsukai, Alternaria solani, Fusarium graminearumt , potato late blight,  Sclerotinia scleotiorum, Botrytis cinerea, Rhizoctonia solani, Phytophthora capsici, Fusarium fujikuroi, Rhizoctonia cereali, Bipolaria maydis  and  Colletotrichum orbiculare.    
         [0091]    The compounds shown in general formula (I) of the present invention can be used as insecticides and bactericides directly, or used by adding an agriculturally acceptable vector, or used in combination with other insecticides, miticides and bactericides, such as: tebufenpyrad, chlorfenapyr, etoxazole and fenpyroximate etc. Some of these compositions show a synergistic effect and some show an additive effect. 
     
    
     DETAILED DESCRIPTION OF THE EMBODIMENTS 
       [0092]    The following embodiments and bioassay results are intended to further illustrate but not to limit the present invention. 
       Embodiment 1 
     Synthesis of Dihydro-β-Carboline Alkaloid Harmalan 
       [0093]    
       
                 
         
             
             
         
       
     
       Synthesis of Indol-3-Formaldehyde 
       [0094]    Add 140 mL of DMF to a 500 mL single-necked flask, add 27 mL of POCl 3  at 0° C., then add 50 mL of DMF solution containing 25 g (214 mmol) of indole and stir them overnight. Add 50 mL of water and 150 mL of 20% NaOH aqueous solution in turn and heat and reflux them for 6 h. Pour the reaction solution into water and conduct suction filtration to obtain 20.6 g of brown solid. The yield is 66% and the melting point is 190-192° C. (literature value: 190-192° C.); 
         [0095]      1 H NMR (400 MHz, CDCl 3 ) 
         [0096]    δ 10.08 (s, 1H, CHO), 8.80 (s, 1H, NH), 8.32-8.34 (m, 1H, Ar—H), 7.86 (d,  3 J HH =2.8 Hz, 1H, Ar—H), 7.44-7.62 (m, 1H, Ar—H), 7.31-7.36 (m, 2H, Ar—H). 
       Synthesis of (E)-3-(Nitrovinyl) Indole 
       [0097]    Add 20 g (138 mmol) of indol-3-formaldehyde, 5.3 g (69 mmol) of ammonium acetate and 200 mL of nitromethane to a 500 mL single-necked flask, and heat and reflux them for 8 h. Add 200 mL of water and 150 mL of ethyl acetate and separate the liquid. Wash the organic phase with water, dry it and evaporate the solvent under a reduced pressure. Use dichloromethane for column chromatography under normal pressure to obtain 19.1 g of yellow solid. The yield is 74% and the melting point is 170-171° C.; 
         [0098]      1 H NMR (400 MHz, CDCl 3 ) δ 8.74 (s, 1H, NH), 8.30 (d,  3 J HH =13.6 Hz, 1H, CH), 7.79-7.83 (m, 2H, CH and Ar—H), 7.69 (d,  3 J HH =2.8 Hz, 1H, Ar—H), 7.48-7.50 (m, 1H, Ar—H), 7.33-7.38 (m, 2H, Ar—H). 
       Synthesis of Tryptamine 
       [0099]    Add 500 mL of tetrahydrofuran to a 1000 mL single-necked flask, and add 11.4 g (300 mmol) of lithium aluminum hydride and 9.4 g (50 mmol) of (E)-3-(nitrovinyl) indole. Heat and reflux them for 7 h. Use water to quench lithium aluminum hydride not fully reacted. Conduct suction filtration, remove the solvent in the filtrate and add ethyl acetate and water to separate liquid. Wash the organic phase with a saturated saline solution, dry it with anhydrous sodium sulfate, remove solvent to obtain a red viscous substance, and dry it naturally to obtain 8.9 g of brown solid. The yield is 89% and the melting point is 115-117° C.; 
         [0100]      1 H NMR (400 MHz, CDCl 3 ) δ 8.26 (s, 1H, NH), 7.62 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.36 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.20 (t,  3 J HH =7.6 Hz, 1H, Ar—H), 7.12 (t,  3 J HH =7.3 Hz, 1H, Ar—H), 7.02 (s, 1H, Ar—H), 3.04 (t,  3 J HH =6.4 Hz, 2H, CH 2 ), 2.91 (t,  3 J HH =6.8 Hz, 2H, CH 2 ), 1.47 (s, 2H, NH 2 ). 
       Synthesis of Harmalan 
       [0101]    Add 0.5 g (3.13 mmol) of tryptamine, 40 mL of dichloromethane and 2 mL of triethylamine to a 100 mL single-necked flask. Add 5 mL of dichloromethane solution containing 0.27 g (3.44 mmol) of acetylchloride and react at room temperature for 5 h. Wash the reaction solution with a saturated sodium bicarbonate aqueous solution, dry it with anhydrous sodium sulfate and remove the solvent. Add 20 mL of toluene, 20 mL of chloroform and 3 mL of phosphorus oxychloride without the need of purification. Heat and reflux them for 7 h. Add sodium carbonate to regulate the reaction solution to be alkaline. Extract the reaction solution with dichloromethane, and wash the organic phase with a saturated saline solution, dry it with anhydrous sodium sulfate and remove the solvent. Use dichloromethane/methanol (10:1) for column chromatography under normal pressure to obtain 0.35 g of brownish yellow solid. The yield is 60% and the melting point is 110-113° C.; 
         [0102]      1 H NMR (400 MHz, CDCl 3 ) δ 9.47 (s, 1H, NH), 7.60 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.48 (d,  3 J HH =8.4 Hz, 1H, Ar—H), 7.31 (t,  3 J HH =8.0 Hz, 1H, Ar—H), 7.16 (t,  3 J HH =8.0 Hz, 1H, Ar—H), 3.88 (t,  3 J HH =8.4 Hz, 2H, CH 2 ), 2.95 (t,  3 J HH =8.8 Hz, 2H, CH 2 ), 2.53 (s, 3H, CH 3 ), HRMS (ESI) calcd for C 32 H 13 N 2 (M+H) +  185.1073. found 185.1077. 
       Embodiment 2 
     Synthesis of Tetrahydroharmane and Harmane 
       [0103]    
       
                 
         
             
             
         
       
     
       Synthesis of Tetrahydroharmane 
       [0104]    Add 8.1 mL (43.75 mmol) of 40% acetaldehyde aqueous solution, 250 mL of water and 5 drops of concentrated sulfuric acid to a 500 mL single-necked flask. Stir them at room temperature for 0.5 h, add 3.50 g (21.88 mmol) of tryptamine and heat and reflux them for 7 h. Add NaOH to regulate pH value to around 10, extract the solution with dichloromethane, wash the organic phase with a saturated saline solution, dry it with anhydrous sodium sulfate, remove the solvent, and use dichloromethane/methanol (5:1) for column chromatography under normal pressure to obtain 2.53 g of brown solid. The yield is 62% and the melting point is 173-175° C.; 
         [0105]      1 H NMR (400 MHz, d 6 -DMSO) δ 10.68 (s, 1H, NH), 7.35 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.27 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 6.98-7.02 (m, 1H, Ar—H), 6.97-6.95 (m, 1H, Ar—H), 3.99-4.04 (m, 1H, CHNH), 3.33 (s, 1H, CHNH), 3.14-3.19 (m, 1H, CH 2 NH), 2.81-2.87 (m, 1H, CH 2 NH), 2.51-2.62 (m, 2H, CH 2 CH 2 ), 1.36 (d,  3 J HH =6.8 Hz, 3H, CH 2 CH), HRMS (ESI) calcd for C 12 H 12 N 2 (M+H) +  187.1230. found 187.1231. 
       Synthesis of Harmane 
       [0106]    Add 0.85 g (4.57 mmol) of tetrahydrocarboline, 0.53 g (4.57 mmol) of maleic acid, 120 mL of water and 0.85 g of Pd/C to a 250 mL single-necked flask. Heat and reflux them for 8 h, conduct suction filtration, wash with water and regulate pH value of the filtrate with NaOH to 9-10 to obtain a large amount of white solid. Conduct suction filtration to obtain 0.5 g of white solid. The yield is 60% and the melting point is 244-245° C.; 
         [0107]      1 H NMR (400 Mhz, CDCl 3 ) δ 8.41 (s, 1H, NH), 8.37 (d,  3 J HH =5.2 Hz, 1H, Ar—H), 8.12 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.83 (d,  3 J HH =5.2 Hz, 1H, Ar—H), 7.52-7.57 (m, 2H, Ar—H), 7.26-7.32 (m, 1H, Ar—H), 2.84 (s, 3H, CH 3 ), HRMS (ESI) calcd for C 12 H 11 N 2 (M+H) +  183.0917. found 183.0915. 
       Embodiment 3 
     Synthesis of Tetrahydroharmine 
       [0108]    
       
                 
         
             
             
         
       
     
       Synthesis of Quaternary Ammonium Salt 
       [0109]    Add 0.5 g (2.36 mmol) of harmine, 120 mL of ethyl acetate and 0.48 g (2.83 mmol) of benzyl bromide to a 250 mL single-necked flask. Heat and reflux them for 12 h. Conduct suction filtration to obtain 0.67 g of light yellow solid. The yield is 74% and the melting point is above 300° C.; 
         [0110]      1 H NMR (400 Mhz, d 6 -DMSO) δ 12.78 (s, 1H, NH), 8.74 (d,  3 J HH =6.4 Hz, 1H, Ar—H), 8.58 (d,  3 J HH =6.8 Hz, 1H, Ar—H), 8.37 (d,  3 J HH =8.8 Hz, 1H, Ar—H), 7.35-7.44 (m, 3H, Ar—H), 7.23 (d,  3 J HH =7.2 Hz, 2H, Ar—H), 7.12 (d,  3 J HH =1.0 Hz, 1H, Ar—H), 7.08 (dd,  3 J HH =8.8 Hz,  3 J HH =1.0 Hz, 1H, Ar—H), 5.98 (s, 2H, CH 2 ), 3.95 (s, 3H, OCH 3 ), 2.98 (s, 3H, CH 3 ). 
       Synthesis of N-Benzyl Tetrahydroharmine 
       [0111]    Add 0.67 g (1.75 mmol) of quaternary ammonium salt and 150 mL of methanol to a 250 mL single-necked flask, and add 30 mL of methanol solution containing 0.53 g (14.0 mmol) of sodium borohydride. Heat and reflux them for 15 h. Remove the solvent and add dichloromethane and water to separate liquid. Wash the organic phase with a saturated saline solution, dry it with anhydrous sodium sulfate, remove the solvent, and use dichloromethane/methanol (20:1) for column chromatography under normal pressure to obtain 0.47 g of brown solid. The yield is 88% and the melting point is 147-149° C.; 
         [0112]      1 H NMR (400 MHz, CDCl 3 ) δ 7.68 (s, 1H, NH), 7.50-7.52 (m, 2H, Ar—H), 7.43-7.47 (m, 3H, Ar—H), 7.36-7.40 (m, 1H, Ar—H), 6.90 (dd,  3 J HH =8.8 Hz,  3 J HH =2.4 Hz, 1H, Ar—H), 6.83 (d,  3 J HH =2.4 Hz, 1H, Ar—H), 3.97 (d,  3 J HH =13.6 Hz, 1H, CH 2 C 6 H 5 ), 3.81 (q,  3 J HH =6.8 Hz, 1H, CHCH 3 ), 3.77 (d,  2 J HH =13.6 Hz, 1H, CH 2 C 6 H 5 ), 3.22-3.29 (m, 1H, CH 2 CH 2 ), 2.85-2.95 (m, 2H, CH 2 CH 2 ), 2.68-2.74 (m, 1H, CH 2 CH 2 ), 1.61 (d,  3 J HH =6.8 Hz, 1H, CHCH 3 ). 
       Synthesis of Tetrahydroharmine 
       [0113]    Add 0.70 g (2.29 mmol) of N-benzyl-protected tetrahydroharmine, 120 mL of trifluoroethanol and 0.70 g of Pd/C to a 250 mL single-necked flask, input hydrogen and stir them overnight. Remove the solvent, and use dichloromethane/methanol (10:1) for column chromatography under normal pressure to obtain 0.37 g of light yellow viscous substance. The yield is 80% and the melting point is 195-197° C.; 
         [0114]      1 H NMR (400 MHz, CDCl 3 ) δ 7.64 (s, 1H, NH), 7.35 (d,  3 J HH =8.8 Hz, 1H, Ar—H), 6.85 (d,  3 J HH =2.0 Hz, 1H, Ar—H), 6.77 (dd,  3 J HH =8.4 Hz,  3 J HH =2.4 Hz, 1H, Ar—H), 4.14-4.19 (m, 1H, CHCH 3 ), 3.84 (s, 3H, OCH 3 ), 3.33-3.39 (m, 1H, CH 2 CH 2 ), 3.01-3.07 (m, 1H, CH 2 CH 2 ), 2.66-2.78 (m, 2H, CH 2 CH 2 ), 1.65 (s, 1H, NH), 1.44 (d,  3 J HH =6.8 Hz, 3H, CH 3 ), HRMS (ESI) calcd for C 33 H 37 N 2 O(M+H) +  217.1335. found 217.1337. 
       Embodiment 4 
     Synthesis of Harmol 
       [0115]    
       
                 
         
             
             
         
       
     
         [0116]    Add 0.5 g (2.36 mmol) of harmine, 18 mL of glacial acetic acid and 18 mL of 40% hydrobromic acid aqueous solution to a 100 mL single-necked flask, and heat and reflux them for 10 h. Use saturated sodium bicarbonate to regulate pH value to around 8 and generate precipitate. Conduct suction filtration to obtain 0.46 g of yellow green solid. The yield is 98% and the melting point is above 300° C.; 
         [0117]      1 H NMR (400 MHz, d 6 -DMSO) δ 11.24 (s, 1H, NH), 9.72 (s, 1H, OH), 8.11 (d,  3 J HH =5.2 Hz, 1H, Ar—H), 7.94 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.75 (d,  3 J HH =5.2 Hz, 1H, Ar—H), 6.90 (d,  4 J HH =1.2 Hz, 1H, Ar—H), 6.69 (dd,  3 J HH =8.4 Hz,  4 J HH =1.6 Hz, 1H, Ar—H), 2.69 (s, 3H, CH 3 ), HRMS (ESI) calcd for C 12 H 11 N 2 O(M+H) +  199.0866. found 199.0867. 
       Embodiment 5 
     Synthesis of Bromo and Nitro-Substituted Harmane 
     Synthesis of Bromo-Harmane (I a -1 and I a -2) 
       [0118]    
       
                 
         
             
             
         
       
     
         [0119]    Add of 0.2 g (1.10 mmol) of harman and 10 mL of glacial acetic acid to a 25 mL single-necked flask, add 0.2 g (1.10 mmol) of NB S, and react at room temperature for 6 h. Remove the solvent, wash with saturated sodium bicarbonate, extract with dichloromethane, dry the organic phase with anhydrous sodium sulfate, remove the solvent and use dichloromethane/methanol (40:1→20:1) in turn for column chromatography under normal pressure to obtain two kinds of white solid: solid I a -1 0.05 g, yield 17%;  1 H NMR (400 MHz, CDCl 3 ) δ 8.36-8.49 (m, 2H, NH and Ar—H), 8.04 (d,  3 J HH =6.4 Hz, 1H, Ar—H), 7.77-7.84 (m, 1H, Ar—H), 7.70 (d,  3 J HH =6.4 Hz, 1H, Ar—H), 7.18 (t,  3 J HH =6.4 Hz, 1H, Ar—H), 2.88 (s, 3H, CH 3 ). Solid I a 2 0.24 g, yield 83%, melting point 256-257° C.; 
         [0120]      1 H NMR (400 MHz, CDCl 3 ) δ 8.44 (s, 1H, NH), 8.39 (d,  3 J HH =5.6 Hz, 1H, Ar—H), 8.24 (d,  4 J HH =2.0 Hz, 1H, Ar—H), 7.78 (d,  3 J HH =5.6 Hz, 1H, Ar—H), 7.63 (dd,  3 J HH =8.4 Hz,  4 J HH =2.0 Hz, 1H, Ar—H), 7.42 (d,  3 J HH =8.8 Hz, 1H, Ar—H), 2.83 (s, 3H, CH 3 ), HRMS (ESI) calcd for C 12 H 13 BrN 2 (M+H) +  261.0022. found 261.0026. 
       Synthesis of Nitro-Substituted Harmane 
     I c -3 and I a -4 
       [0121]    
       
                 
         
             
             
         
       
     
         [0122]    Add 0.4 g (2.20 mmol) of harman and 0.93 g (10.99 mmol) of sodium nitrate to a 50 mL single-necked flask, add 20 mL of trifluoroacetic acid, and stir them at room temperature for 6 h. Add a saturated sodium bicarbonate aqueous solution to the reaction solution to regulate pH value to 10-11 and generate yellow precipitate, and conduct suction filtration to obtain 0.06 g of yellow solid I a -3. The yield is 12% and the melting point is 207-210° C. 
         [0123]      1 H NMR (400 MHz, d 6 -DMSO) δ 11.77 (s, 1H, NH), 8.77 (d,  3 J HH =7.6 Hz, Ar—H), 8.50 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 8.38 (d,  3 J HH =5.2 Hz, 1H, Ar—H), 8.11 (d,  3 J HH =5.2 Hz, 1H, Ar—H), 7.48 (t,  3 J HH =7.6 Hz, 1H, Ar—H), 2.92 (s, 3H, CH 3 ), HRMS (ESI) calcd for C 12 H 19 N 3 O 3 (M+H) +  228.0768. found 228.0772, 0.36 g. 
         [0124]    0.36 g of light yellow solid I a -4. The yield is 12% and the melting point is above 300° C. 
         [0125]      1 H NMR (400 MHz, d 6 -DMSO) δ 12.36 (s, 1H, NH), 9.30 (d,  4 J HH =2.0 Hz, 1H, Ar—H), 8.41 (dd,  3 J HH =8.8 Hz,  3 J HH =3.0 Hz, 1H, Ar—H), 8.33 (d,  3 J HH =5.6 Hz, 1H, Ar—H), 8.20 (d,  3 J HH =5.2 Hz, 1H, Ar—H), 7.73 (d,  3 J HH =8.4 Hz, 1H, Ar—H), 2.79 (s, 3H, CH 3 ), HRMS (ESI) calcd for C 12 H 10 N 3 O 2 (M+H) −  228.0768. found 228.0767. 
       Embodiment 6 
     Synthesis of isopropylamino formate (1-methylpyridino[3,4-b]indol-7)-ester (I a -5) 
       [0126]    
       
                 
         
             
             
         
       
     
         [0127]    Add 0.5 g (2.53 mmol) of demethylated harmaline and 50 mL of DMF to a 100 mL single-necked flask, add 1.5 mL of isopropyl isocyanate and 0.08 g (0.758 mmol) of triethylamine, and stir them overnight. Add a saturated sodium chloride aqueous solution, extract with ethyl acetate, dry it with anhydrous sodium sulfate and remove the solvent. Use dichloromethane/methanol (20:1) for column chromatography under normal pressure to obtain 0.50 g of white solid. The yield is 70% and the melting point is above 300° C.; 
         [0128]      1 H NMR (400 MHz, d 6 -DMSO) δ 11.58 (s, 1H, NH), 8.20 (d,  3 J HH =5.2 Hz, 1H, Ar—H), 8.16 (d,  3 J HH =8.8 Hz, 1H, Ar—H), 7.90 (d,  3 J HH =5.2 Hz, 1H, Ar—H), 7.76 (d,  3 J HH =8.0 Hz, 1H, NHCO), 7.27 (d,  4 J HH =1.6 Hz, 1H, Ar—H), 6.95 (dd,  3 J HH =8.4 Hz,  4 J HH =2.0 Hz, 1H, Ar—H), 3.65-3.73 (m, 1H, CH), 2.75 (s, 3H, CH 3 ), 1.16 (d,  3 J HH =3.4 Hz, 6H, (CH 3 ) 3 CH), HRMS (ESI) calcd for C 16 H 14 N 2 O 2 (M+H) +  284.1394. found 284.1399. 
       Embodiment 7 
     Synthesis of dimethylcarbamate (1-methylpyridino[3,4-b]indol-7)-ester (I a -6) 
       [0129]    
       
                 
         
             
             
         
       
     
         [0130]    Add 0.4 g (2.02 mmol) of demethylated harmaline, 150 mL of tetrahydrofuran, 0.31 g (3.03 mmol) of triethylamine and a catalytic amount of DMAP to a 250 mL single-necked flask, stir them at room temperature for 0.5 h, add 0.33 g (3.03 mmol) of acyl chloride and stir them overnight. Remove the solvent, add dichloromethane and water to separate liquid, wash the organic phase with a saturated saline solution, dry it with anhydrous sodium sulfate, remove the solvent, and use dichloromethane/methanol (10:11) for column chromatography under normal pressure to obtain 0.48 g of white solid. The yield is 89% and the melting point is 225-227° C.; 
         [0131]      1 H NMR (400 MHz, d 6 -DMSO) δ 11.63 (s, 1H, NH), 8.20 (d,  3 J HH =5.2 Hz, 1H, Ar—H), 8.17 (d,  3 J HH =8.4 Hz, 1H, Ar—H), 7.91 (d,  3 J HH =5.2 Hz, 1H, Ar—H), 7.30 (d,  3 J HH =2.0 Hz, 1H, Ar—H), 6.97 (dd,  3 J HH =8.4 Hz,  4 J HH =2.0 Hz, 1H, Ar—H), 3.10 (s, 3H, CH 3 ), 2.94 (s, 3H, CH 3 ), 2.75 (s, 3H, CH 3 ), HRMS (ESI) calcd for C 15 H 16 N 3 O 2 (M+H) +  270.1237. found 270.1240. 
         [0132]    Compounds I a -7-I a -8 are completed through repeating the foregoing steps 
       Acetate (1-methylpyridino[3,4-b]indol-7)-ester (I a -7) 
       [0133]    White solid, yield 50%, melting point 237-240° C.; 
         [0134]      1 H NMR (400 MHz, CDCl 3 ) δ 8.90 (s, 1H, NH), 8.23 (d,  3 J HH =2.4 Hz, 1H, Ar—H), 7.78 (d,  3 J HH =8.4 Hz, 1H, Ar—H), 7.70 (d,  3 J HH =2.0 Hz, 1H, Ar—H), 7.16 (s, 1H, Ar—H), 6.93 (d,  3 J HH =8.4 Hz, 1H, Ar—H), 2.76 (s, 3H, CH 3 ), 2.42 (s, 3H, CH 3 CO), HRMS (ESI) calcd for C 14 H 13 N 2 O 2 (M+H) +  241.0972. found 241.0970. 
       Tert-valerate (1-methylpyridino[3,4-b]indol-7)-ester (I a -8) 
       [0135]    White solid, yield 85%, melting point 221-222° C.; 
         [0136]      1 H NMR (400 MHz, CDCl 3 ) δ 8.68 (s, 1H, NH), 8.30 (d,  3 J HH =5.2 Hz, 1H, Ar—H), 7.75 (d,  3 J HH =8.4 Hz, 1H, Ar—H), 7.54 (d,  3 J HH =4.8 Hz, 1H, Ar—H), 7.09 (s, 1H, Ar—H), 6.86 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 2.73 (s, 3H, CH 3 ), 1.45 (s, 9H, C(CH 3 ) 3 ), HRMS (ESI) calcd for C 17 H 13 N 2 O 2 (M+H) +  283.1441. found 283.1446. 
       Embodiment 8 
     Synthesis of (S)-3-methyl-2-carbobenzoxyaminobutyrate-(1-methylpyridino[3,4-b]indol-7-ester (I a -9) 
       [0137]    
       
                 
         
             
             
         
       
     
         [0138]    Add 0.80 g (3.03 mmol) of amino acid and 150 mL of dichloromethane to a 250 mL single-necked flask, and add 0.41 g (4.04 mmol) of triethylamine, 0.76 g (4.04 mmol) of EDCI (1-ethyl-(3-dimethylaminopropyl) carbonyldiimide hydrochloride) and 0.50 g (4.04 mmol) of DMAP (4-dimethylaminopyridine) and stir them overnight. Wash them with water, dry them with anhydrous sodium sulfate, remove the solvent, and use dichloromethane/methanol (20:1) for column chromatography under normal pressure to obtain 0.8 g of white solid. The yield is 92% and the melting point is 69-71° C.; 
         [0139]      1 H NMR (400 MHz, CDCl 3 ) δ 8.54 (s, 1H, NH), 8.54 (d,  3 J HH =5.2 Hz, 1H, Ar—H), 7.92 (d,  3 J HH =8.4 Hz, 1H, Ar—H), 7.66 (d,  3 J HH =4.8 Hz, 1H, Ar—H), 7.35-7.38 (m, 5H, Ar—H), 7.19 (s, 1H, Ar—H), 6.94 (d,  3 J HH =8.4 Hz, 1H, Ar—H), 5.39 (d,  3 J HH =8.4 Hz, 1H, Ar—H), 5.17 (s, 2H, CH 2 ), 4.54-4.66 (m, 1H, CHNH), 2.77 (s, 3H, CH 3 ), 2.38-2.50 (m, 1H, CH(CH 3 ) 2 ), 1.14 (d,  3 J HH =6.8 Hz, 3H, CH(CH 3 ) 3 ), 1.09 (d,  3 J HH =6.8 Hz, 3H, CH(CH 3 ) 2 ), HRMS (ESI) calcd for C 23 H 25 N 3 O 4 (M+H) +  432.1918. found 432.1920. 
       Embodiment 9 
     (1S,3S)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formic acid (I b -1) 
       [0140]    
       
                 
         
             
             
         
       
     
         [0141]    Add 20 g (98.0 mmol) of L-tryptophan, 500 mL of water, 2 mL of concentrated sulfuric acid and 20 mL of 40% acetaldehyde aqueous solution to a 1000 mL single-necked flask, stir them at room temperature overnight, use strong aqua to regulate pH value to 6-7, separate out white solid and conduct suction filtration to obtain 16.7 g of white solid. The yield is 74% and the melting point is 78-280° C.; 
         [0142]      1 H NMR (400 MHz, d 6 -DMSO) Γ 11.11 (s, 1H, COOH), 7.45 (d,  3 J HH =7.8 Hz, 1H, Ar—H), 7.34 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.09 (t,  3 J HH =7.6 Hz, 1H, Ar—H), 7.00 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.52 (q,  3 J HH =6.4 Hz, 1H, CH), 3.61 (dd,  3 J HH =11.6 Hz,  3 J HH =4.4 Hz, 1H, CH), 3.16 (dd,  2 J HH =16.0 Hz,  3 J HH =4.0 Hz, 1H, CH 2 ), 2.74-2.81 (m, 1H, CH 2 ), 1.62 (d,  3 J HH =6.4 Hz, 3H, CH 3 ); HRMS (ESI) calcd for C 23 H 35 N 2 O 2 (M+H) +  231.1128. found 231.1132. 
         [0143]    Compounds I b -2 and I b -3 are completed through repeating the foregoing steps 
       (1R,3R)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formic acid (I b -2) 
       [0144]    White solid, yield 76%, melting point 285-287° C.; 
         [0145]      1 H NMR (400 MHz, d 6 -DMSO) δ 11.20 (s, 1H, COOH), 7.44 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.35 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.09 (t,  3 J HH =7.6 Hz, 1H, Ar—H), 7.00 (t,  3 J HH =7.6 Hz, 1H, Ar—H), 4.56 (q,  4 J HH =6.4 Hz, 1H, CHCH 3 ), 3.64 (dd,  3 J HH =12.0 Hz,  3 J HH =4.8 Hz, 1H, CH), 3.18 (dd,  3 J HH =16.0 Hz,  3 J HH =4.4 Hz, 1H, CH 3 ), 2.76-2.83 (m, 1H, CH 2 ), 1.64 (d,  3 J HH =6.4 Hz, 3H, CH 3 ); HRMS (ESI) calcd for C 13 H 18 N 2 O 2 (M+H) +  231.1128. found 231.1132. 
       (1S,3S)-1-ethyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formic acid (I b -3) 
       [0146]    2.67 g of white solid, yield 44%, melting point 277-280° C.; 
         [0147]      1 H NMR (400 MHz, d 6 -DMSO) δ 10.92 (s, 1H, COOH), 7.43 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.35 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.05-7.08 (m, 1H, Ar—H), 6.96-7.00 (m, 1H, Ar—H), 4.32-4.33 (m, H, CHNH), 3.54 (dd,  3 J HH =11.6 Hz,  3 J HH =4.4 Hz, 1H, CHCO), 3.10 (dd,  3 J HH =15.6 Hz,  3 J HH =4.0 Hz, 1H, CH 2 ), 2.70-2.78 (m, 1H, CH 2 ), 2.12-2.20 (m, 1H, CH 2 CH 3 ), 1.83-1.90 (m, 1H, CH 2 CH 3 ), 1.01 (t,  3 J HH =7.2 Hz, 3H, CH 2 CH 3 ). HRMS (ESI) calcd for C 19 H 17 N 2 O 2 (M+H) +  245.1285. found 245.1289. 
       Embodiment 10 
     Synthesis of 2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formic acid (I b -4) 
       [0148]    
       
                 
         
             
             
         
       
     
         [0149]    Add 10.00 g (49 mmol) of L-tryptophan, 1.96 g (49 mmol) of NaOH and 100 mL of water to a 250 mL single-necked flask, and add 5 mL of 30° A formaldehyde aqueous solution. Heat and reflux them for 3 h. Use 3M diluted hydrochloric acid to regulate pH value to around 5 and generate precipitate, conduct suction filtration, wash the filter cakes with water and dry them to obtain 8.32 g of white solid. The yield is 88% and the melting point is 278-279° C.; 
         [0150]      1 H NMR (400 MHz, d 6 -DMSO) δ 10.97 (s, 1H, COOH), 7.45 (d,  3 J HH =7.8 Hz, 1H, Ar—H), 7.34 (d,  3 J HH =8.0 Hz, 1H Ar—H) 7.09 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 7.00 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.25 (d,  2 J HH =15.6 Hz, 1H, NHCH 2 ), 4.18 (d,  3 J HH =15.6 Hz, 1H, NHCH 3 ), 3.62 (dd,  3 J HH =10.4 Hz,  3 J HH =4.8 Hz, 1H, CH), 3.15 (dd,  3 J HH =16.4 Hz,  3 J HH =4.8 Hz, 1H, CH 2 ), 2.83 (dd,  3 J HH =15.6 Hz,  3 J HH =10.8 Hz, 1H, CH 3 ), HRMS (ESI) calcd for C 12 H 13 N 2 O 2 (M+H) +  217.0972. found 217.0969. 
       Embodiment 11 
     Synthesis of (1S,3S)-1-phenyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formic acid (I b -5) 
       [0151]    
       
                 
         
             
             
         
       
     
         [0152]    Add 2.5 g (12.3 mmol) of L-tryptophan, 50 mL of glacial acetic acid and 1.5 g (13.5 mmol) of benzaldehyde to a 100 mL single-necked flask, heat and reflux them for 12 h, remove the solvent, use ammonium hydroxide to regulate pH value to 5-6 and generate precipitate, and conduct suction filtration to obtain 3.1 g of white solid. The yield is 86% and the melting point is 197-207° C.; 
         [0153]      1 H NMR (400 MHz, d 6 -DMSO) δ 10.46 (s, 1H, COOH), 7.46 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.39-7.41 (m, 5H, Ar—H), 7.23 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.03 (t,  3 J HH =6.8 Hz, 1H, Ar—H), 6.98 (t,  3 J HH =7.6 Hz, 1H, Ar—H), 5.43 (s, 1H, CH), 4.95 (br, 1H, NH), 3.80 (dd,  3 J HH =11.2 Hz,  3 J HH =4.0 Hz, 1H, CH), 3.14 (dd,  3 J HH =18.4 Hz,  3 J HH =3.2 Hz, 1H, CH 3 ), 2.86-2.92 (m, 1H, CH 2 ), HRMS (ESI) calcd for C 18 H 17 H 2 O 2 (M+H) +  293.1285. found 293.1286. 
         [0154]    Compound I b -6 is completed through repeating the foregoing steps. 
       (1S,3S)-1-(pyridine-3)-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formic acid (I b -6) 
       [0155]    Yellow solid, yield 87% and the melting point is 250-253° C.; 
         [0156]      1 H NMR (400 MHz, DMSO-d 6 ) δ 10.48 (s, 1H, COOH), 8.60 (d,  3 J HH =1.6 Hz, 1H, Ar—H), 8.56 (dd,  3 J HH =4.8 Hz,  4 J HH =1.6 Hz, 1H, Ar—H), 7.70 (dt,  3 J HH =8.0 Hz,  4 J HH =1.6 Hz, 1H, Ar—H), 7.47 (dd,  3 J HH =4.8 Hz,  3 J HH =8.0 Hz, 1H, Ar—H), 7.20 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.00-7.04 (m, 1H, Ar—H), 6.96-6.99 (m, 1H, Ar—H), 5.37 (s, 1H, CHAr), 3.79 (dd,  3 J HH =11.2 Hz,  3 J HH =4.0 Hz, 1H, CHCOOH), 3.06-3.11 (m, 1H, CH 2 ), 2.81-2.88 (m, 1H, CH 2 ). HRMS (ESI) calcd for C 17 H 16 N 3 O 3 (M+H) +  294.1237. found 294.1237. 
       Embodiment 12 
     Synthesis of (1S,3S)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-ethyl formate (I b -13) 
       [0157]    
       
                 
         
             
             
         
       
     
         [0158]    Add 16 g (69.0 mmol) of acid and 500 mL of anhydrous ethanol to a 1000 mL single-necked flask, add 30 mL of thionyl chloride, and heat and reflux them for 5 h. Use a saturated sodium bicarbonate aqueous solution to regulate pH value to 9 and generate precipitate, and conduct suction filtration to obtain 16.4 g of milky solid, The yield is 92% and the melting point is 136-137° C.; 
         [0159]      1 H NMR (400 MHz, CDCl 3 ) δ 7.86 (s, 1H, NH), 7.49 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.33 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.17 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 7.11 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.26-4.31 (m, 3H, CH and OCH 2 ), 3.81 (dd,  3 J HH =11.2 Hz,  3 J HH =4.4 Hz, 1H, CH), 3.13 (dd,  2 J HH =15.2 Hz,  3 J HH =4.0 Hz, 1H, CH 2 ), 2.79-2.86 (m, 1H, CH 2 ), 1.52 (d,  3 J HH =6.4 Hz, 3H, CH 2 ), 1.35 (t,  3 J HH =7.2 Hz, 3H, OCH 2 CH 3 ), HRMS (ESI) calcd for C 18 H 18 N 2 O 2 (M+H) +  259.1441. found 259.1443. 
         [0160]    Compounds I b -7-I b -12 are completed through repeating the foregoing steps 
       (S)-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-ethyl formate (I b -7) 
       [0161]    Light yellow solid, yield 95%, melting point 50-53° C.; 
         [0162]      1 H NMR (400 MHz, CDCl 3 ) δ 7.81 (s, 1H, NH), 7.48 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.32 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.17 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 7.11 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.25-4.30 (m, 3H, CH and OCH 2 ), 3.83-3.86 (m, 4H, CH and OCH 3 ), 3.11-3.16 (m, 1H, CH 2 ), 2.80-2.87 (m, 1H, CH 2 ), 1.51 (d,  3 J HH =6.8 Hz, 3H, CH 3 ), HRMS (ESI) calcd for C 16 H 16 N 2 O 2 (M+H) +  245.1285. found 245.1288. 
       (1S,3S)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-butyl formate (I b -8) 
       [0163]    Yellow oily substance, yield 68%; 
         [0164]      1 H NMR (400 MHz, CDCl 3 ) δ 7.78 (s, 1H, NH), 7.49 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.33 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.17 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 7.11 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.26-4.31 (m, 1H, CHCH 2 ), 4.23 (t,  3 J HH =6.8 Hz, 2H, CH 2 O), 3.82 (dd,  3 J HH =7.2 Hz,  3 J HH =4.4 Hz, 1H, CHCO), 3.10-3.16 (m, 1H, CH 2 ), 2.78-2.85 (m, 1H, CH 2 ), 1.67-1.74 (m, 2H, OCH 2 CH 2 ), 1.52 (d,  3 J HH =6.8 Hz, 3H, CHCH 3 ), 1.41-1.48 (m, 2H, CH 2 CH 3 ), 0.97 (t,  3 J HH =7.2 Hz, 3H, CH 2 CH 3 ). HRMS (ESI) calcd for C 17 H 23 N 2 O 2 (M+H) +  287.1754. found 287.1759. 
       2,3,4,9-tetrahydropyridino[3,4-b]indol-3-ethyl formate (I b -9) 
       [0165]    Yellow solid, yield 90%, melting point 136-137° C.; 
         [0166]      1 H NMR (400 MHz, CDCl 3 ) δ 7.80 (s, 1H, NH), 7.49 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.31 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.16 (d,  3 J HH =7.2 Hz,  4 J HH =4.8 Hz, 1H, Ar—H), 7.08-7.12 (m, 1H, Ar—H), 4.26 (q,  3 J HH =6.8 Hz, 2H, OCH 3 ), 4.10-4.19 (m, 2H, CH 2 NH), 3.79 (q,  3 J HH =4.8 Hz, 1H, CHCO), 3.14 (q, 1H,  3 J HH =7.2 Hz, 1H, CHCO 2 Et), 3.14 (dd,  2 J HH =15.2 Hz,  3 J HH =4.8 Hz, 1H, CH 2 ), 2.85-2.96 (d,  3 J HH =6.4 Hz, 1H, CH 2 ), 1.93 (br, 1H, NH), 1.33 (t,  3 J HH =6.8 Hz, 3H, OCH 2 CH 3 ), HRMS (ESI) calcd for C 17 H 23 N 2 O 2 (M+H) +  245.1285. found 245.1280. 
       (1S,3S)-1-ethyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-ethyl formate (I b -10) 
       [0167]    Yellow oily substance, yield 68%; 
         [0168]      1 H NMR (400 MHz, CDCl 3 ) δ 7.49 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.33 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.14-7.18 (m, 1H, Ar—H), 7.09-7.13 (m, 1H, Ar—H), 4.26-4.32 (m, 2H, OCH 3 ), 4.15-4.18 (m, H, CHNH), 3.78 (dd,  3 J HH =11.2 Hz,  3 J HH =4.0 Hz, 1H, CHCO), 3.11-3.16 (m, 1H, CH 2 ), 2.77-2.84 (m, 1H, CH 2 ), 1.71-1.84 (m, 2H, CH 3 CH 2 ), 1.35 (t,  3 J HH =7.2 Hz, 3H, OCH 2 CH 3 ), 1.90 (t,  3 J HH =7.2 Hz, 3H, CH 2 CH 3 ), HRMS (ESI) calcd for C 16 H 21 N 2 O 2 (M+H) +  273.1598. found 273.1602. 
       (1S,3S)-1-(pyridine-3)-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-ethyl formate (I b -11) 
       [0169]    White solid, yield 42%, melting point 239-240° C.; 
         [0170]      1 H NMR (400 MHz, CDCl 3 ) δ 8.62 (d,  3 J HH =1.6 Hz, 1H, Ar—H), 8.55 (dd,  3 J HH =4.4 Hz,  4 J HH =1.6 Hz, 1H, Ar—H), 7.94 (s, 1H, NH), 7.72 (dt,  3 J HH =7.6 Hz,  3 J HH =1.6 Hz, 1H, Ar—H), 7.55-7.58 (m, 1H, Ar—H), 7.24-7.29 (m, 2H, Ar—H), 7.11-7.19 (m, 2H, Ar—H), 5.31 (s, 1H, CHAr), 4.28-4.31 (m, 2H, OCH 2 CH 2 ), 3.97 (dd,  3 J HH =11.2 Hz,  3 J HH =4.0 Hz, 1H, CHCOOMe), 3.26 (ddd,  3 J HH =14.8 Hz,  3 J HH =4.0 Hz,  4 J HH =1.6 Hz, 1H, CH 2 ), 2.98-3.05 (m, 1H, CH 2 ), 1.35 (t,  3 J HH =6.8 Hz, 3H, OCH 2 CH 3 ), HRMS (ESI) calcd for C 19 H 20 N 3 O 2 (M+H) +  322.1550. found 322.1552. 
       (1R,3R)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-ethyl formate (I b -12) 
       [0171]    Light yellow solid, yield 92%, melting point 121-122° C.; 
         [0172]      1 H NMR (400 MHz, CDCl 3 ) δ 7.83 (s, 1H, NH), 7.49 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.32 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.16 (d,  3 J HH =7.2 Hz,  4 J HH =1.2 Hz, 1H, Ar—H), 7.11 (td,  3 J HH =7.2 Hz,  4 J HH =0.8 Hz, 1H, Ar—H), 4.26-4.31 (m, 3H, CH and OCH 2 ), 3.81 (dd,  3 J HH =11.2 Hz,  3 J HH =4.4 Hz, 1H, CH), 3.13 (ddd,  3 J HH =15.2 Hz,  3 J HH =4.4 Hz,  4 J HH =2.0 Hz, 1H, CH 2 ), 2.82 (ddd,  3 J HH =14.8 Hz,  3 J HH =11.2 Hz,  4 J HH =2.4 Hz, 1H, CH 2 ), 1.51 (d,  3 J HH =6.8 Hz, 3H, CH 3 ), 1.35 (t,  3 J HH =7.2 Hz, 3H, OCH 3 CH 3 ), HRMS (ESI) calcd for C 13 H 19 N 2 O 2 (M+H) +  259.1441. found 259.1443. 
       Embodiment 13 
     1-methyl-pyridino[3,4-b]indol-3-ethyl formate (I a -10) and 1-methyl-pyridino[3,4-b]indol-3-formic acid (I a -11) 
       [0173]    
       
                 
         
             
             
         
       
     
       1-methyl-pyridino[3,4-b]indol-3-ethyl formate (I a -10) 
       [0174]    Add 12.4 g (47.7 mmol) of tetrahydrocarboline, 3.1 g (95.4 mmol) of elemental sulfur and 150 mL of xylol to a 250 mL single-necked flask, and heat and reflux them for 12 h. Cool them to separate out flesh pink solid, and conduct suction filtration to obtain 8.4 g of flesh color solid. Yellow solid, yield 69%, melting point 217-219° C.; 
         [0175]      1 H NMR (400 MHz, CDCl 3 ) δ 9.60 (s, 1H, NH), 8.79 (s, 1H, Ar—H), 8.18 (d,  3 J HH =8.0 Hz, Ar—H), 7.54-7.60 (m, 2H, Ar—H), 7.32-7.36 (m, 1H, Ar—H), 4.50 (d,  3 J HH =6.8 Hz, 2H, OCH 2 ), 2.79 (s, 3H, CH 3 ), 1.41 (t,  3 J HH =7.2 Hz, 3H, OCH 2 CH 3 ), HRMS (ESI) calcd for C 15 H 19 N 2 O 2 (M+H) +  227.0815. found 227.0811. 
       1-methyl-pyridino[3,4-b]indol-3-formic acid (I a -11) 
       [0176]    Add 2.00 g (7.87 mmol) of ester, 0.47 g (11.81 mmol) of NaOH and 60 mL of ethanol to a 100 mL single-necked flask, and heat and reflux them for 6 h. Use 3M diluted hydrochloric acid to regulate pH value to 5-6 and generate precipitate, conduct suction filtration, wash filter cakes with water and dry them to obtain 1.46 g of light yellow solid. The yield is 82% and the melting point is above 300° C.; 
         [0177]      1 H NMR (400 MHz, d 6 -DMSO) δ 12.04 (s, 1H, COOH), 8.77 (s, 1H, Ar—H), 8.36 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.66 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.60 (t,  3 J HH =7.0 Hz, 1H, Ar—H), 7.30 (d,  3 J HH =7.2 Hz, 1H, Ar—H), 7.31 (d,  3 J HH =7.2 Hz, 1H, Ar—H), 2.82 (s, 3H, CH 3 ). HRMS (ESI) calcd for C 13 H 11 N 2 O 2 (M+H) +  255.1128. found 255.1131. 
       Embodiment 14 
     Synthesis of (E)-3-(1-methyl-pyridino[3,4-b]indol-3)-acrylic acid (I a -14) 
       [0178]    
       
                 
         
             
             
         
       
     
       (1-methyl-pyridino[3,4-b]indol-3)-methanol (I a -12) 
       [0179]    Add 2 g (7.4 mmol) of ester and 300 mL of tetrahydrofuran to a 500 mL single-necked flask, add 0.6 g (15.7 mmol) of lithium aluminum hydride by batch, stir them at room temperature overnight, add water to quench the reaction, conduct suction filtration and remove the solvent of the filtrate to obtain 1.58 g of yellow solid. The yield is 95% and the melting point is 195-197° C.; 
         [0180]      1 H NMR (400 MHz, d 6 -DMSO) δ 11.46 (s, 1H, NH), 8.19 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.95 (s, 1H, Ar—H), 7.56 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.49-7.53 (m, 1H, Ar—H), 7.18-7.22 (m, 1H, Ar—H), 5.30 (t,  3 J HH =6.0 Hz, 1H, OH), 4.67 (d,  3 J HH =6.0 Hz, 2H, CH 2 OH), 2.73 (s, 3H, CH 3 ). 
       1-methyl-pyridino[3,4-b]indol-3-formaldehyde (I a -13) 
       [0181]    Add 1.16 g (5.47 mmol) of alcohol, 3.04 g (10.93 mmol) of IBX and 60 mL of DMSO to a 100 mL single-necked flask, and stir them at room temperature overnight. Add 200 mL of water, use dichloromethane for extraction, wash the organic phase with a saturated saline solution, dry it with anhydrous sodium sulfate, remove the solvent, and use dichloromethane/methanol (10:1) for column chromatography under normal pressure to obtain 0.46 g of white solid. The yield is 40% and the melting point is 194-196° C.; 
         [0182]      1 H NMR (400 MHz, d 6 -DMSO) δ 12.17 (s, 1H, NH), 10.07 (s, 1H, CHO), 8.68 (s, 1H, Ar—H), 8.38 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.68 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.61 (t,  3 J HH =7.6 Hz, 1H, Ar—H), 7.33 (t,  3 J HH =7.6 Hz, 1H, Ar—H), 2.87 (s, 3H, CH 3 ). 
       (E)-3-(1-methyl-pyridino[3,4-b]indol-3)-acrylic acid (I a -14) 
       [0183]    Add 0.45 g (2.14 mmol) of aldehyde, 100 mL of pyridine and 3 drops of piperidine to a 250 mL single-necked flask, add 0.33 g (3.21 mmol) of malonic acid, and heat and react for 4 h. Use 3M diluted hydrochloric acid to regulate pH value of the water phase to 5-6, and conduct suction filtration to obtain 0.51 g of yellow solid. The yield is 94% and the melting point is 220-223° C.;  1 H NMR (400 MHz, d 6 -DMSO) δ 12.22 (s, 1H, NH), 11.85 (s, 1H, COOH), 8.31 (s, 1H, Ar—H), 8.21 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.72 (d,  3 J HH =15.2 Hz, 1H, CHCH), 7.62 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.56 (t,  3 J HH =7.6 Hz, 1H, Ar—H), 7.28 (t,  3 J HH =7.6 Hz, 1H, Ar—H), 6.78 (d,  3 J HH =15.6 Hz, 1H, CHCH), 2.80 (s, 3H, CH 2 ); HRMS (ESI) calcd for C 15 H 13 N 2 O 2 (M+H) +  253.0972. found 253.0975. 
         [0184]    Compounds I a -15-I a -16 are completed through repeating the foregoing steps 
       (E)-3-(1-(thiophene-2)-pyridino[3,4-b]indol-3)-acrylic acid (I a -15) 
       [0185]    Yellow solid, yield 85%, melting point 248-250° C.; 
         [0186]      1 H NMR (400 MHz, d 6 -DMSO) δ 12.43 (s, 1H, NH), 12.10 (s, 1H, COOH), 8.47 (s, 1H, Ar—H), 8.28 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 8.17 (d,  3 J HH =3.2 Hz, 1H, Ar—H), 7.80 (d,  3 J HH =4.8 Hz, 1H, Ar—H), 7.77-7.80 (m, 2H, Ar—H), 7.62 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 7.33-7.38 (m, 2H, Ar—H and CHCH), 6.88 (d,  3 J HH =15.6 Hz, 1H, CHCH), 6.93 (d,  3 J HH =15.6 Hz, 1H, CHCH); HRMS (ESI) calcd for C 18 H 32 N 2 O 2 (M+H) +  321.0692. found 321.0694. 
       (E)-3-(1-(pyridine-3)-pyridino[3,4-b]indol-3)-acrylic acid (I a -16) 
       [0187]    Yellow solid, yield 50%, melting point&gt;300° C.; 
         [0188]      1 H NMR (400 MHz, d 6 -DMSO) δ 12.43 (s, 1H, NH), 12.10 (s, 1H, COOH), 9.31 (d,  3 J HH =1.6 Hz, 1H, Ar—H), 8.81 (dd,  3 J HH =4.8 Hz, 1H, Ar—H), 8.61 (s, 1H, Ar—H), 8.56-8.59 (m, 1H, Ar—H), 8.31 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.84 (d,  3 J HH =15.6 Hz, 1H, CHCH), 7.76 (dd,  3 J HH =7.6 Hz,  3 J HH =4.8 Hz, 1H, Ar—H), 7.70 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.62 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 7.35 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 6.93 (d,  3 J HH =15.6 Hz, 1H, CHCH), 
       Embodiment 15 
     Synthesis of 1-methyl-4,9-dihydro-pyridino[3,4-b]indol-3)-ethyl formate (I b -14) 
       [0189]    
       
                 
         
             
             
         
       
     
       L-tryptophan ethyl ester (6) 
       [0190]    Add 0.50 g (24.50 mmol) of L-tryptophan and 150 mL of ethanol to a 250 mL single-necked flask, add 15 mL of thionyl chloride, and heat and reflux them for 12 h. Remove the solvent to obtain 5.72 g of brown viscous substance, with a yield of 98%; 
         [0191]      1 H NMR (400 MHz, CDCl 3 ) δ 8.10 (s, 1H, NH), 7.62 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.37 (d,  3 J HH =80 Hz, 1H, Ar—H), 7.20 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 7.13 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 7.08 (s, 1H, Ar—H), 4.14-4.19 (m, 2H, OCH 2 ), 3.82 (dd,  3 J HH =7.6 Hz,  3 J HH =5.2 Hz, 1H, CH), 3.29 (dd,  3 J HH =14.4 Hz,  3 J HH =5.2 Hz, 1H, CH 2 ), 3.05 (dd,  3 J HH =14.4 Hz,  3 J HH =8.0 Hz, 1H, CH 2 ), 1.24 (t,  3 J HH =7.2 Hz, 3H, OCH 2 CH 3 ). 
       1-methyl-4, 9-dihydro-pyridino[3,4-b]indol-3-ethyl formate (I b -14) 
       [0192]    Add 5.72 g (24.66 mmol) of tryptophan ethyl ester, 150 mL of dichloromethane and 2.99 g (29.59 mmol) of triethylamine to a 250 mL single-necked flask, add 2.13 g (27.12 mmol) of acetylchloride and stir them at room temperature for 5 h after dropwise addition. Use a saturated sodium bicarbonate to wash the reaction solution, extract with dichloromethane, wash the organic phase with a saturated saline solution, dry it with anhydrous sodium sulfate and remove the solvent to obtain 5.96 g of brown viscous substance. Dissolve it in chloroform, add 24 mL of POCl 3 , and heat and reflux them for 5 h. Extract with dichloromethane, dry with anhydrous sodium sulfate, remove the solvent, and use dichloromethane/methanol (10:1) for column chromatography under normal pressure to obtain 2.85 g of yellow solid. Yellow solid, yield 45%, melting point 85-87° C.; 
         [0193]      1 H NMR (400 MHz, CDCl 3 ) δ 8.33 (s, 1H, NH), 7.61 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.41 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.30 (t,  3 J HH =8.0 Hz, 1H, Ar—H), 7.17 (t,  3 J HH =8.0 Hz, 1H, Ar—H), 4.43-4.48 (m, 1H, CHCO 2 Et), 4.31 (q,  3 J HH =7.2 Hz, OCH 2 ), 3.25 (dd,  3 J HH =16.4 Hz,  3 J HH =7.6 Hz, 1H, CH 2 CH), 3.08 (dd,  3 J HH =16.4 Hz,  3 J HH =14.8 Hz, 1H, CH 2 CH), 2.43 (d,  3 J HH =2.0 Hz, 3H, CH 3 ), 1.34 (t,  3 J HH =7.2 Hz, 3H, OCH 2 CH 3 ), HRMS (ESI) calcd for C 15 H 17 N 2 O 2 (M+H) +  247.1285. found 257.1287. 
       Embodiment 16 
     (1S,3S)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I b -15) 
       [0194]    
       
                 
         
             
             
         
       
     
         [0195]    Add 1.00 g (4.1 mmol) of methyl ester, 50 mL of ethanol and 1.02 g (16.4 mmol) of 80% hydrazine hydrate to a 100 mL single-necked flask, and heat and reflux them for 6 h. Remove the solvent, dissolve it in ethyl acetate, wash it with a saturated saline solution, dry it with anhydrous sodium sulfate, and remove the solvent to obtain 0.98 g of light yellow solid, with a yield of 98%. White solid, yield 98% and melting point 100-103° C.; 
         [0196]      1 H NMR (400 MHz, CDCl 3 ) δ 8.15 (s, 1H, NH), 7.90 (s, 1H, NHCO), 7.50 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.32 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.17 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 7.11 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.18-4.23 (m, 1H, CHCH 3 ), 3.93 (br, 2H, NH 2 ), 3.65 (q,  3 J HH =8.4 Hz, 1H, CHCO), 3.26-3.32 (m, 1H, CH 2 ), 2.71-2.78 (m, 1H, CH 2 ), 1.48 (d,  3 J HH =6.8 Hz, 3H, CH 3 ), HRMS (ESI) calcd for C 13 H 12 N 4 O(M+H) +  245.1397. found 245.1398. 
       Embodiment 17 
     Synthesis of (1S,3S)—N-butyl-1-methyl-2,3,4,9-tetrahydro-pyridino[3,4-b]indol-3-formamide (I b -16) 
       [0197]    
       
                 
         
             
             
         
       
     
         [0198]    Add 0.5 g (2.05 mmol) of methyl ester and 15 mL of n-butylamine to a 25 mL single-necked flask, and stir them at room temperature overnight. Remove the solvent, add dichloromethane to dissolve it, wash it with a saturated saline solution, dry with anhydrous sodium sulfate and remove the solvent. Use dichloromethane/methanol (20:1) for column chromatography under normal pressure to obtain 0.35 g of white solid. The yield is 60% and the melting point is 207-210° C.; 
         [0199]      1 H NMR (400 MHz, CDCl 3 ) δ 8.02 (s, 1H, NH), 7.49 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.31 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.15 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 7.10 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.17-4.22 (m, 1H, CHCH 3 ), 3.58 (dd,  3 J HH =11.2 Hz,  3 J HH =4.4 Hz, 1H, CHCO), 3.28-3.38 (m, 3H, CHCH 2  and NHCH 2 ), 2.37-2.74 (m, 1H, CH 3 ), 1.51-1.59 (m, 2H, NHCH 2 CH 2 ), 1.49 (d,  3 J HH =10.8 Hz, 3H, CHCH 3 ), 1.34-1.43 (m, 2H, CH 2 CH 3 ), 0.95 (t,  3 J HH =7.22 Hz, 3H, CH 2 CH 3 ); HRMS (ESI) calcd for C 13 H 24 N 2 O(M+H) +  286.1914. found 286.1919. 
         [0200]    Compound I b -18 is completed through repeating the foregoing steps 
       (1S,3S)—N-(2-ethoxyl)-1-methyl-2,3,4,9-tetrahydro-pyridino[3,4-b]indol-3-formamide (I b -18) 
       [0201]    White solid, yield 64%, melting point 110-112° C.; 
         [0202]    1H NMR (400 MHz, d 6 -methanol) δ 7.39 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.29 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.04-7.07 (m, 1H, Ar—H), 6.95-6.99 (m, 1H, Ar—H), 4.18 (q,  3 J HH =6.8 Hz, 1H, CHCH 3 ), 3.67 (t,  3 J HH =6.4 Hz, 2H, HOCH 2 ), 3.62 (dd,  3 J HH =11.2 Hz,  3 J HH =4.4 Hz, 1H, CHCO), 3.38-3.42 (m, 3H, NHCH 2 ), 3.30-3.32 (m, 1H, ?), 3.02-3.08 (m, 1H, CH 2 CHCO), 2.72-2.80 (m, 1H, CH 2 CHCO), 1.52 (d,  3 J HH =6.8 Hz, 3H, CHCH 3 ); HRMS (ESI) calcd for C 13 H 30 N 2 O 2 (M+H) +  274.1550. found 274.1552. 
       Embodiment 18 
     Synthesis of (1S,3S)—N-cyclohexyl-1-methyl-2,3,4,9-tetrahydro-pyridino[3,4-b]indol-3-formamide (I b -17) 
       [0203]    
       
                 
         
             
             
         
       
     
         [0204]    White solid, yield 50%, melting point 231-233° C.; 
         [0205]      1 H NMR (400 MHz, CDCl 3 ) δ 7.81 (s, 1H, NH), 7.51 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.32 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.14-7.18 (m, 1H, Ar—H), 7.09-7.13 (m, 1H, Ar—H), 6.94 (d,  3 J HH =8.0 Hz, 1H, NHCO), 4.19-4.24 (m, 1H, CHCH 3 ), 3.79-3.88 (m, 1H, NHCH), 3.57 (dd,  3 J HH =11.2 Hz,  3 J HH =4.8 Hz, 1H, CHCO), 3.28-3.33 (m, 1H, COCHCH 2 ), 2.67-2.74 (m, 1H, COCHCH 2 ), 1.93-1.99 (m, 2H, CH 2 ), 1.73-1.73 (m, 2H, CH 3 ), 1.58-1.67 (m, 2H, CH 2 ), 1.50 (d,  3 J HH =8.0 Hz, 3H, CHCH 3 ), 1.36-1.43 (m, 2H, CH 2 ), 1.18-1.26 (m, 2H, CH 3 ), HRMS (ESI) calcd for C 19 H 36 N 9 O(M+H) +  312.2070. found 312.2076. 
         [0206]    Compounds I b -19, I b -20 are completed through repeating the foregoing steps 
       (1S,3S)—N-((dimethyl amino)methyl)-1-methyl-2,3,4,9-tetrahydro-pyridino[3,4-b]indol-3-formamide (I b -19) 
       [0207]    White solid, yield 55%; 
         [0208]    mp=110-112° C.;  1 H NMR (400 MHz, CDCl 3 ) δ 7.87 (s, 1H, Ar—NH), 7.51 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.32 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.28 (m, 1H, CONH), 7.16 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 7.11 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.22 (q,  3 J HH =6.8 Hz, 1H, CH), 3.61 (d,  3 J HH =4.4 Hz,  3 J HH =11.2 Hz, 1H, CH), 3.51-3.36 (m, 2H, N—CH 2 ), 3.28 (ddd,  3 J HH =2.0 Hz,  3 J HH =4.4 Hz,  2 J HH =16.0 Hz, 1H, CH 2 ), 2.74 (ddd,  4 J HH =2.4 Hz,  3 J HH =11.2 Hz,  2 J HH =160 Hz, 1H, CH 2 ), 2.48 (t,  3 J HH =6.4 Hz, 2H, CH 2 ), 2.27 (s, 6H, CH 3 ), 1.50 (d,  3 J HH =6.8 Hz, 3H, CH 2 ); HRMS (ESI) calcd for C 17 H 23 N 4 O(M+H) +  301.2023. found 301.2027. 
       (1S,3S)—N-((tetrahydrofuran-2)-methyl)-1-methyl-2,3,4,9-tetrahydro-pyridino[3,4-b]indol-3-formamide (I b -20) 
       [0209]    Yellow solid, yield 47%, melting point 95-97° C.; 
         [0210]      1 H NMR (400 MHz, CDCl 3 ) δ 7.81 (s, 1H, NH), 7.55 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.40-7.45 (m, 1H, NHCO), 7.36 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.20 (t,  3 J HH =7.6 Hz, 1H, Ar—H), 7.14 (t,  3 J HH =7.6 Hz, 1H, Ar—H), 4.25 (q,  3 J HH =6.8 Hz, 1H, CHCH 3 ), 4.04-4.10 (m, 1H, CHO), 3.90-3.95 (m, 1H, CH 2 O), 3.83 (dd,  3 J HH =7.2 Hz,  3 J HH =15.2 Hz, 1H, CHCO), 3.63-3.70 (m, 2H, CH 2 O and CH 2 NH), 3.35 (dd,  3 J HH =16.0 Hz,  3 J HH =4.4 Hz, 1H, CH 2 CH), 3.18-3.30 (m, 1H, CH 2 NH), 2.72-2.79 (m, 1H, CH 2 CH), 2.02-2.98 (m, 1H, CH 2 CH 2 ), 1.92-1.99 (m, 2H, CH 2 CH 2 ), 1.59-1.65 (m, 1H, CH 2 CH 2 ), 1.53 (d,  3 J HH =6.8 Hz, 3H, CHCH 3 ), HRMS (ESI) calcd for C 18 H 23 N 2 O 1 (M+H) +  314.1863. found 314.1867. 
       Embodiment 19 
     (1S,3S)—N′-benzylidene-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -1) 
       [0211]    
       
                 
         
             
             
         
       
     
         [0212]    Add 0.50 g (2.05 mmol) of hydrazide and 40 mL of toluene to a 100 mL single-necked flask, add 0.44 g (4.10 mmol) of benzaldehyde, and heat and reflux them for 5 h. Conduct suction filtration and wash with toluene to obtain 0.50 g of yellow solid. The yield is 74% and the melting point is 200-204° C.; 
         [0213]      1 H NMR (400 MHz, DMSO-d 6 ) δ 11.48 and  3 J HH =7.6 Hz, 1H, Ph-H), 7.49-7.42 (m, 2H, Ph-H), 7.42-7.33 (m, 2H, Ph-H and Ar—H), 7.31 and 7.30 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.03 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 6.95 and 6.92 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.48 and 3.61 (dd,  3 J HH =10.8 Hz, 3.6 Hz, 1H, CH), 4.15 (d,  3 J HH =8.0 Hz, 1H, CH), 2.98-2.89 (m, 1H, CH 2 ), 2.71 and 2.62 (ddd,  3 J HH =2.0 Hz,  3 J HH =11.6 Hz,  3 J HH =14.4 Hz, 1H, CH 2 ), 1.45 (d,  3 J HH =6.8 Hz, 3H, CH 3 ), HRMS (ESI) calcd for C 30 H 21 N 4 O[M+H] +  333.1710. found 333.1715. 
         [0214]    Compounds I c -2-I c -29 are completed through repeating the foregoing steps 
       (1S,3S)—N′-(4-tert-butyl benzylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -2) 
       [0215]    Yellow solid, yield 72%, melting point 139-143° C.; 
         [0216]      1 H NMR (400 MHz, DMSO-d 6 ) δ 11.47 and 11.32 (s, 1H, NH), 10.87 and 10.82 (s, 1H, O═C—NH), 8.31 and 8.03 (s, 1H, N═CH), 7.88 and 7.70-7.27 (m, 6H, Ph-H and Ar—H), 7.04 (t,  3 J HH =6.8 Hz, 1H, Ar—H), 6.96 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.48 and 3.62 (dd,  3 J HH =10.4 Hz, 7.2 Hz, 1H, CH), 4.27-4.08 (m, 1H, CH), 3.02-2.88 (m, 1H, CH 2 ), 2.77-2.39 (m, 1H, CH 2 ), 1.52-1.35 (m, 3H, CH 3 ), 1.30 and 1.24 (s, 9H, CH 3 ); HRMS (ESI) calcd for C 24 H 29 N 4 O(M+H) +  289.2336. found 389.2338. 
       (1S,3S)—N′-(4-dimethyl amino benzylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -3) 
       [0217]    Yellow solid, yield 73%, melting point 215-220° C.; 
         [0218]      1 H NMR (400 MHz, DMSO-d 6 ) δ 11.20 and 11.05 (s, 1H, NH), 10.84 and 10.80 (s, 1H, O═C—NH), 8.16 and 7.92 (s, 1H, N═CH), 7.52 and 7.36 (d,  3 J HH =7.6 Hz, 2H, Ph-H), 7.44-7.38 (m, 1H, Ar—H), 7.30 (d,  3 J HH =6.4 Hz, 1H, Ar—H), 7.03 (t,  3 J HH =6.8 Hz, 1H, Ar—H), 6.95 (t,  3 J HH =6.8 Hz, 1H, Ar—H), 6.75 and 6.67 (d,  3 J HH =7.0 Hz, 2H, Ph-H), 4.44 and 3.57 (d,  3 J HH =8.8 Hz, 1H, CH), 4.23-4.08 (m, 1H, CH), 3.07-2.86 (m, 7H, N—CH 3  and CH 2 ), 2.74-2.56 (m, 1H, CH 2 ), 1.52-1.38 (m, 3H, CH 3 ); HRMS (ESI) calcd for C 32 H 30 N 5 O [M+H] +  376.2132. found 376.2137. 
       (1S,3S)—N′-(4-nitrobenzylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -4) 
       [0219]    Yellow solid, yield 74%, melting point 222-227° C.; 
         [0220]      1 H NMR (400 MHz, DMSO-d 6 ) δ 11.81 and 11.68 (s, 1H, NH), 10.87 and 10.82 (s, 1H, O═C—NH), 8.46 and 8.17 (s, 1H, N═CH), 8.31 and 8.22 (d,  3 J HH =8.4 Hz, 2H, Ph-H), 7.98 and 7.88 (d,  3 J HH =8.4 Hz, 2H, Ph-h), 7.41 and 7.36 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.31 (d,  3 J HH =6.4 Hz, 1H, Ar—H), 7.04 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 6.96 (t,  3 J HH =7.6 Hz, 1H, Ar—H), 4.55 and 3.67 (d,  3 J HH =8.8 Hz, 1H, CH), 4.25-4.10 (m, 1H, CH), 2.86 (d,  3 J HH =13.6 Hz, 1H, CH 2 ), 2.79-2.60 (m, 1H, CH 2 ), 1.47 (d,  3 J HH =6.4 Hz, 3H, CH 2 ); HRMS (ESI) calcd for C 20 H 30 N 3 O[M+H] +  378.1561. found 378.1563. 
       (1S,3S)—N′-(4-chlorobenzylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -5) 
       [0221]    Yellow solid, yield 81%, melting point 140-145° C.; 
         [0222]      1 H NMR (400 MHz, DMSO-d 6 ) δ 11.62 and 11.51 (s, 1H, NH), 10.91 and 10.85 (s, 1H, O═C—CH), 8.35 and 8.07 (s, 1H, N═CH), 7.74 and 7.64 (d,  3 J HH =7.2 Hz, 2H, Ph-H), 7.58-7.35 (m, 3H, Ph-H and Ar—H), 7.35-7.28 (m, 1H, Ar—H), 7.10-7.00 (m, 1H, CH 2 ), 2.79-2.62 (m, 1H, CH 2 ), 1.54-1.39 (m, 3H, CH 3 ); HRMS (ESI) calcd for C 21 H 20 N 2 OCl[M+H] +  367.1320. found 367.1323. 
       (1S,3S)—N′-(2, 4-dichlorobenzylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -6) 
       [0223]    yellow solid, yield 85%, melting point 211-213° C.; 
         [0224]      1 H NMR (400 MHz, DMSO-d 6 ) δ 11.82 and 11.77 (s, 1H, NH), 10.91 and 10.84 (s, 1H, O═C—NH), 8.71 and 8.42 (s, 1H, N═CH), 8.00 and 7.85 (d,  3 J HH =8.4 Hz, 1H, Ph-H), 7.73 and 7.71 (d,  3 J HH =2.0 Hz, 1H, Ph-H), 7.53 and 7.43-7.35 (dd,  4 J HH =2.0 Hz,  3 J HH =8.4 Hz, 1H, Ph-H), 7.41 and 7.37 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.32 and 7.31 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.04 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 6.96 and 6.94 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.65-4.56 and 3.66 (dd,  3 J HH =10.4 Hz, 6.3 Hz, 1H, CH), 4.35-4.13 (m, 1H, CH), 3.06-2.91 (m, 1H, CH 2 ), 2.78-2.64 (m, 1H, CH 2 ), 1.54-1.43 (m, 3H, CH 3 ); HRMS (ESI) calcd for C 20 H 19 N 4 OCl 2 [M+H] +  401.0931. found 401.0929. 
       (1S,3S)—N′-(3,4-dichlorobenzylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -7) 
       [0225]    Yellow solid, yield 79%, melting point 189-193° C.; 
         [0226]      1 H NMR (400 MHz, DMSO-d 6 ) δ 11.84 and 11.67 (s, 1H, NH), 10.98 and 10.86 (s, 1H, O═C—NH), 8.34 and 8.07 (s, 1H, N═CH), 7.94 and 7.88 (s, 1H, Ph-H), 7.72 and 7.64 (s, 2H, Ph-H), 7.41 and 7.39 (d,  3 J HH =8.4 Hz, 1H, Ar—H), 7.33 and 7.31 (d,  3 J HH =8.4 Hz, 1H, Ar—H), 7.06 and 7.04 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 6.96 and 6.96 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.68 and 3.70 (dd,  3 J HH =10.4 Hz, 4.4 Hz, 1H, CH), 4.38 and 4.19 (q,  3 J HH =6.4 Hz, 1H, CH), 3.06 and 2.98 (dd,  3 J HH =6.6 Hz,  3 J HH =14.4 Hz, 1H, CH 2 ), 2.80-2.66 (m, 1H, CH 2 ), 1.53 and 1.48 (d,  3 J HH =6.4 Hz, 3H, CH 3 ); HRMS (ESI) calcd for C 20 H 19 N 4 OCl 3 [M+H] +  401.0931. found 401.0934. 
       (1S,3S)—N′-(4-methoxybenzylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -8) 
       [0227]    Yellow solid, yield 69%, melting point 138-143° C.; 
         [0228]      1 H NMR (400 MHz, DMSO-d 6 ) δ 11.35 and 11.22 (s, 1H, NH), 10.84 and 10.81 (s, 1H, O═C—NH), 8.27 and 8.00 (s, 1H, N═CH), 7.65 and 7.55 (d,  3 J HH =8.0 Hz, 2H, Ph-H), 7.40 and 7.36 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.30 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.08-6.89 (m, 4H, Ar—H and Ph-H), 4.45 and 3.59 (d,  3 J HH =8.8 Hz, 1H, CH), 4.20-4.08 (m, 1H, CH), 3.81 and 3.74 (s, 3H, O═CH 2 ), 2.93 (d,  2 J HH =14.4 Hz, 1H, CH 2 ), 2.76-2.56 (m, 1H, CH 3 ), 1.45 (d,  5 J HH =6.0 Hz, 3H, CH 3 ), HRMS (ESI) calcd for C 21 H 23 N 4 O 2 [M+H] +  363.1816. found 363.1819. 
       (1S,3S)—N′-(3-methoxybenzylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -9) 
       [0229]    Yellow solid, yield 63%, melting point 186-190° C.; 
         [0230]      1 H NMR (400 MHz, DMSO-d 6 ) δ 11.54 and 11.39 (s, 1H, NH), 10.87 and 10.83 (s, 1H, O═C—NH), 8.32 and 8.03 (s, 1H, N═CH), 7.45-7.11 (m, 5H, Ph-H and Ar—H), 7.08-8.89 (m, 3H, Ar—H and Ph-H), 4.48 and 3.63 (d,  3 J HH =8.0 Hz, 1H, CH), 4.25-4.10 (m, 1H, CH), 3.81 and 3.69 (s, 3H, O—CH 3 ), 3.02-2.89 (m, 1H, CH 2 ), 2.77-2.60 (m, 1H, CH 2 ), 1.46 (d,  3 J HH =5.2 Hz, 3H, CH 3 ); HRMS (ESI) calcd for C 23 H 23 N 3 O 2 [M+H] +  363.1816. found 363.1818. 
       (1S,3S)—N′-(2-methoxybenzylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -10) 
       [0231]    Yellow solid, yield 82%, melting point 180-183° C.; 
         [0232]      1 H NMR (400 MHz, DMSO-d 6 ) δ 11.52 and 11.46 (s, 1H, NH), 10.90 and 10.84 (s, 1H, O═C—NH), 8.66 and 8.41 (s, 1H, N═CH), 7.84 and 7.68 (d,  3 J HH =7.2 Hz, 1H, Ph-H), 7.41 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.37 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.31 (dd,  3 J HH =8.0 Hz, 1H, Ph-H), 7.14-6.86 (m, 4H, Ph-H and Ar—H), 4.54 and 3.61 (dd,  3 J HH =10.0 Hz, 2.8 Hz, 1H, CH), 4.30-4.10 (m, 1H, CH), 3.86 and 3.84 (s, 3H, O—CH 3 ), 3.04-3.89 (m, 1H, CH 2 ), 2.77-2.60 (m, 1H, CH 2 ), 1.55-1.37 (m, 3H, CH 3 ); HRMS (ESI) calcd for C 21 H 23 N 6 O 2 [M+H] +  363.1816. found 363.1823. 
       (1S,3S)—N′-(3,4-dimethoxybenzylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -11) 
       [0233]    Light yellow solid, yield 91%, melting point 203-206° C.; 
         [0234]      1 H NMR (400 MHz, DMSO-d 6 ) δ 11.47 and 11.27 (s, 1H, NH), 10.89 and 10.83 (s, 1H, O═C—NH), 8.25 and 7.99 (s, 1H, N═CH), 7.43-7.36 (m, 1H, Ar—H), 7.34-7.27 and 7.22-7.15 (m, 3H, Ar—H and Ph-H), 7.07-6.91 (m, 3H, Ar—H and Ph-H), 4.49 and 3.67-3.59 (dd,  3 J HH =11.2 Hz, 3.6 Hz, CH), 4.33-4.11 (m, 1H, CH), 3.82 and 3.75 (s, 3H, O—CH 3 ), 3.81 and 3.64 (s, 3H, O—CH 3 ), 3.03 and 2.94 (dd,  3 J HH =2.8 Hz,  3 J HH =14.8 Hz, 1H, CH 2 ), 2.76-2.65 (m, 1H, CH 2 ) 1.48 and 1.46 (d,  3 J HH =6.8 Hz, 3H, CH 3 ); HRMS (ESI) calcd for C 22 H 23 N 4 O 4 [M+H] +  393.1921. found 393.1918. 
       (1S,3S)—N′-((benzo[d][1,3]dioxymethylene-5)-methylene-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -12) 
       [0235]    Yellow solid, yield 83%, melting point 199-203° C.; 
         [0236]      1 H NMR (400 MHz, DMSO-d 6 ) δ 11.41 and 11.26 (s, 1H, NH), 10.86 and 10.81 (s, 1H, O═C—NH), 8.24 and 7.96 (s, 1H, N═CH), 7.40 and 7.36 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.31 and 7.30 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.28 and 7.17 (s, 1H, Ph-H), 7.15 and 7.09 (d,  3 J HH =8.0 Hz, 1H, Ph-H), 7.06-6.96 (m, 2H, Ar—H and Ph-H), 6.94 (t,  3 J HH =7.6 Hz, 1H, Ar—H), 6.10 (s, 1H, O—CH 2 ), 6.02 (d,  2 J HH =4.8 Hz, 1H, O—CH 2 ), 4.49 and 3.60 (dd,  3 J HH =10.8 Hz, 3.6 Hz, CH), 4.22 and 4.13 (m, 1H, CH), 2.99-2.87 (m, 1H, CH 2 ), 2.75-2.87 (m, 1H, CH 2 ), 1.45 (d,  3 J HH =6.4 Hz, 3H, CH 3 ); HRMS (ESI) calcd for C 21 H 23 N 4 O 3 [M+H] +  377.1608. found 377.1615. 
       (1S,3S)—N′-(2, 3-dihydrobenzo[b][1,4]dioxin-6-methylene)-1-methyl)-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -13) 
       [0237]    Light yellow solid, yield 81%, melting point 204-207° C.; 
         [0238]      1 H NMR (400 MHz, DMSO-d 6 ) δ 11.44 and 11.26 (s, 1H, NH), 10.89 and 10.82 (s, 1H, O═C—NH), 8.21 and 7.94 (s, 1H, c═CH), 7.40 and 7.36 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.32 and 7.30 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.20 and 7.10 (s, 1H, Ph-H), 7.19 and 7.09 (d,  3 J HH =7.6 Hz, 1H, Ph-H), 7.07-7.01 (m, 1H, Ar—H), 6.99-6.83 (m, 2H, Ar—H and Ph-H), 4.51 and 3.61 (dd,  3 J HH =10.8 Hz, 3.6 Hz, 1H, CH), 4.35-4.09 (m, 5H, CH and O—CH 2 —CH 2 —O), 3.03-2.89 (m, 1H, CH 2 ), 2.76-2.60 (m, 1H, CH 2 ), 1.53-1.43 (m, 3H, CH 3 ), HRMS (ESI) calcd for C 22 H 23 N 4 O 2 [M+H] +  391.1765. found 391.1763. 
       (1S,3S)—N′-(6-hydroxynaphthalene-2-methylene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -14) 
       [0239]    Yellow solid, yield 70%, melting point 275-278° C.; 
         [0240]      1 H NMR (400 MHz, DMSO-d 6 ) δ 11.46 and 11.35 (s, 1H, NH), 10.85 and 10.81 (s, 1H, O═C—NH), 9.98 (s, 1H, OH), 8.42 and 8.16 (s, 1H, N═CH), 7.99 and 7.91 (s, 1H, Naphthalene-H), 7.85 (d,  3 J HH =9.2 Hz, 1H, Nahphthalene-H), 7.80 and 7.61 (d,  3 J HH =8.8 Hz, 1H, Naphthalene-H), 7.74 and 7.70 (d,  3 J HH =8.8 Hz, 1H, Naphpthalene-H), 7.42 and 7.37 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.16 and 7.08 (s, 1H, Naphthalene-H), 7.15-7.09 (m, 1H, Naphthalene-H), 7.04 (t,  3 J HH =7.6 Hz, 1H, Ar—H), 7.00-6.90 (m, 1H, Ar—H), 4.52 and 3.63 (d,  3 J HH =8.4 Hz, 1H, CH), 4.25-4.10 (m, 1H, CH), 3.02-2.90 (m, 1H, CH 2 ), 2.73 and 2.65 (t,  3 J HH =12.8 Hz, 1H, CH 2 ), 1.47 (d,  3 J HH =6.0 Hz, 3H, CH 3 ); HRMS (ESI) calcd for C 24 H 23 N 4 O 2 [M+H] +  399.1816. found 399.1822. 
       (1S,3S)—N′-(pyridine-4-methylene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -15) 
       [0241]    Yellow solid, yield 79%, melting point 235-239° C.; 
         [0242]      1 H NMR (400 MHz, DMSO-d 6 ) δ 11.84 and 11.69 (s, 1H, NH), 10.90 and 10.84 (s, 1H, O═C—NH), 8.65 and 8.57 (d,  3 J HH =5.6 Hz, 2H, Py-H), 8.35 and 8.05 (s, 1H, N═CH), 7.65 and 7.57 (d,  3 J HH =5.6 Hz, 2H, Py-H), 7.41 and 7.37 (d,  3 J HH =7.6 Hz, 1H, Ph-H), 7.34-7.29 (m, 1H, Ar—H), 7.04 (t,  3 J HH =7.6 Hz, 1H, Ar—H), 6.95 (t,  3 J HH =7.6 Hz, 1H, Ar—H), 4.58 and 3.67 (dd,  3 J HH =10.8 Hz, 3.6 Hz, 1H, CH), 4.26 and 4.16 (q,  3 J HH =6.4 Hz, 1H, CH), 3.05-2.91 (m, 1H, CH 2 ), 2.80-2.62 (m, 1H, CH 2 ), 1.48 (d,  3 J HH =6.4 Hz, 3H, CH 3 ); HRMS (ESI) calcd for C 25 H 20 N 5 O[M+H] +  334.1662. found 334.1663. 
       (1S,3S)—N′-(pyridine-3-methylene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -16) 
       [0243]    Yellow solid, yield 72%, melting point 205-209° C.; 
         [0244]      1 H NMR (400 MHz, DMSO-d 6 ) δ 11.74 and 11.58 (s, 1H, NH), 10.91 and 10.84 (s, 1H, O═C—NH), 8.84 and 8.79 (s, 1H, Py-H), 8.62 and 8.55 (d,  3 J HH =4.0 Hz, 1H, Py-H), 8.41 and 8.12 (s, 1H, N═CH), 8.12 and 8.03 (d,  3 J HH =4.0 Hz, 1H, Py-H), 7.49 and 7.44-7.35 (m, 2H, Py-H and Ar—H), 7.33 and 7.31 (d,  3 J HH =7.6 Hz, 1H, Ph-H), 7.04 (t,  3 J HH =7.6 Hz, 1H, Ar—H), 6.96 (t,  3 J HH =7.6 Hz, 1H, Ar—H), 4.59 and 3.66 (dd,  3 J HH =10.8 Hz, 3.6 Hz, 1H, CH), 4.32 and 4.12 (m, 1H, CH), 3.85-2.92 (m, 1H, CH 3 ), 2.78-2.63 (m, 1H, CH 3 ), 1.53-1.39 (m, 3H, CH 3 ); HRMS (ESI) calcd for C 29 H 28 N 9 O[M+H] +  334.1662. found 334.1664. 
       (1S,3S)—N′-(pyridine-2-methylene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -17) 
       [0245]    Yellow solid, yield 72%, melting point 245-249° C.; 
         [0246]      1 H NMR (400 MHz, DMSO-d 6 ) δ 11.69 and 11.65 (s, 1H, NH), 10.85 and 10.82 (s, 1H, O—C—NH), 8.62 and 8.57 (d,  3 J HH =4.8 Hz, 1H, Py-H), 8.36 and 8.10 (s, 1H, N═CH), 7.95 and 7.80 (d,  3 J HH =8.0 Hz, 1H, Py-H), 7.88 and 7.75 (td,  3 J HH =1.2 Hz,  3 J HH =7.6 Hz, 1H, Py-H), 7.44-7.33 (m, 2H, Py-H and Ar—H), 7.31 and 7.30 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.03 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 6.95 and 6.92 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.50 and 3.63 (dd,  3 J HH =10.8 Hz, 4.0 Hz, CH), 4.16 (q,  3 J HH =8.9 Hz, 1H, CH), 2.94 (ddd,  3 J HH =1.6 Hz,  3 J HH =4.4 Hz,  2 J HH =14.8 Hz, 1H, CH 2 ), 2.72 and 2.63 (ddd,  4 J HH =2.0 Hz,  4 J HH =10.8 Hz,  2 J HH =14.8 Hz, 1H, CH 2 ), 1.46 and 1.45 (d,  3 J HH =6.8 Hz, 3H, CH 3 ); HRMS (ESI) calcd for C 19 H 20 N 2 O[M+H] +  334.1662. found 334.1666. 
       (1S,3S)—N′-(furan-2-methylene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -18) 
       [0247]    Yellow solid, yield 62%, melting point 144-148° C.; 
         [0248]      1 H NMR (400 MHz, CDCl 3 ) δ 10.33 and 10.20 (s, 1H, NH), 8.26 and 8.11 (s, 1H, O═C—NH), 8.04 and 7.72 (s, 1H, N═CH), 7.51-7.38 (m, 2H, Ar—H and furan-H), 7.34 and 7.31 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.14 (t,  3 J HH =6.8 Hz, 1H, Ar—H), 7.08 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 6.77 and 6.62 (s, 1H, furan-H), 6.45 and 6.42 (s, 1H, furan-H), 4.65 and 3.69 (d,  3 J HH =7.6 Hz, 1H, CH), 4.32-4.11 (m, 1H, CH), 3.30 and 3.19 (d,  3 J HH =13.6 Hz, 1H, CH 2 ), 2.79 (t,  3 J HH =13.2 Hz, 1H, CH 2 ), 1.97 (br, 1H, NH), 1.52 and 1.46 (d,  3 J HH =6.4 Hz, 3H, CH 3 ); HRMS (ESI) calcd for C 18 H 19 N 4 O 2 [M+H] +  323.1503. found 323.1505. 
       (1S,3S)—N′-(pyrrole-2-methylene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine 
       [0249]    Red solid, yield 75%, melting point 207-209° C.; 
         [0250]      1 H NMR (400 MHz, DMSO-d 6 ) δ 11.52 and 11.31 (s, 1H, NH), 11.16 and 11.05 (s, 1H, Pyrrole-NH), 10.83 and 10.80 (s, 1H, O═C—NH), 8.15 and 7.88 (s, 1H, N═CH), 7.45-7.35 (m, 1H, Ar—H), 7.30 (d,  3 J HH =7.2 Hz, 1H, Ar—H), 7.03 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 6.95 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 6.90 and 6.83 (s, 1H, Pyrrole-H), 6.45 and 6.39 (s, 1H, Pyrrole-H), 6.13 and 6.08 (s, 1H, Pyrrole-H), 4.60 and 3.58 (d,  3 J HH =8.8 Hz, 1H, CH), 4.24-4.08 (m, 1H, CH), 2.98-2.88 (m, 1H, CH 2 ), 2.70-2.59 (m, 1H, CH 2 ), 1.50-1.45 (m, 3H, CH 3 ); HRMS (ESI) calcd for C 18 H 20 N 4 O[M+H] +  322.1662. found 322.1668. 
       (1S,3S)—N′-(thiophene-2-methylene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine 
       [0251]    Yellow solid, yield 76%, melting point 139-141° C.; 
         [0252]      1 H NMR (400 MHz, DMSO-d 6 ) δ 11.55 and 11.39 (s, 1H, NH), 10.90 and 10.83 (s, 1H, O═C—NH), 8.56 and 8.24 (s, 1H, N═CH), 7.67 and 7.54 (d,  3 J HH =4.8 Hz, 1H, Thiophene-H), 7.47-7.35 (m, 2H, Thiophene-H and Ar—H), 7.35-7.28 (m, 1H, Ar—H), 7.14 and 7.09 (t,  3 J HH =4.4 Hz, 1H, Thiophene-H), 7.04 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 7.00-6.90 (m, 1H, Ar—H), 4.38 and 3.62 (dd,  3 J HH =8.8 Hz, 4.0 Hz, 1H, CH), 4.29-4.10 (m, 1H, CH), 3.04-2.89 (m, 1H, CH 2 ), 2.77-2.61 (m, 1H, CH 2 ), 1.54-1.38 (m, 3H, CH 3 ); HRMS (ESI) calcd for C 18 H 19 N 1 OS[M+H] +  339.1274. found 339.1278. 
       (1S,3S)—N′-(imidazole-2-methylene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine 
       [0253]    Green solid, yield 81%, melting point 188-190° C.; 
         [0254]      1 H NMR (400 MHz, DMSO-d 6 ) δ 14.10, 13.33, 12.81 and 12.57 (s, 1H, Imidazole-NH), 12.93 and 11.47 (s, 1H, NH), 10.84 and 10.81 (s, 1H, O═C—NH), 8.45, 8.26, 7.95 and 7.44 (s, 1H, N═CH), 7.42-6.88 (m, 6H, Ar—H and Imidazole-H), 4.65, 4.50, 3.69 and 3.63 (m, 1H, CH), 4.37 and 4.17 (m, 1H, CH), 3.03 and 2.95 (d,  3 J HH =14.0 Hz, 1H, CH 2 ), 2.78-2.56 (m 1H, CH 3 ), 1.52-1.42 (m, 3H, CH 3 ); HRMS (ESI) calcd for C 37 H 19 N 6 O[M+H] +  323.1615. found 323.1620. 
       (1S,3S)—N′-((E)-but-2-enylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -22) 
       [0255]    Yellow solid, yield 61%, melting point 145-148° C.; 
         [0256]      1 H NMR (400 MHz, CDCl 3 ) δ 10.10 and 9.63 (s, 1H, NH), 8.23 and 8.15 (s, 1H, O═C—NH), 7.72 and 7.37 (d,  3 J HH =8.4 Hz, 1H, N═CH), 4.57-4.48 and 3.70-3.58 (m, 1H, CH), 4.31-4.06 (m, 1H, CH), 3.27 and 3.12 (d,  3 J HH =14.4 Hz, 1H, CH 2 ), 2.85-2.66 (m, 1H, CH 2 ), 2.09 (br, 1H, NH), 1.92-1.75 (m, 3H, CH 3 ), 1.50 and 1.43 (d,  3 J HH =5.6 Hz, 3H, CH 3 ); HRMS (ESI) calcd for C 18 H 20 N 5 O[M+H] +  297.1710. found 297.1714. 
       (1S,3S)—N′-butylidene-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -23) 
       [0257]    Yellow solid 0.52 g, yield 71%, melting point 113-117° C.; 
         [0258]      1 H NMR (400 MHz, DMSO-d 6 ) δ 11.04 and 10.97 (s, 1H, NH), 10.82 and 10.80 (s, 1H, O═C—NH), 7.59 and 7.42-7.33 (m, 3H, N═CH and Ar—H), 7.30 (d,  3 J HH =7.6 Hz, 1H, Ph-H), 7.03 (t,  3 J HH =6.8 Hz, 1H, Ar—H), 6.95 (t,  3 J HH =6.8 Hz, 1H, Ar—H), 4.28 and 3.51 (d,  3 J HH =9.6 Hz, 1H, CH), 4.19-4.04 (m, 1H, CH), 2.89 (d,  3 J HH =14.0 Hz, 1H, CH 2 ), 2.67 and 2.57 (t,  2 J HH =12.8 Hz, 1H, CH 2 ), 2.25-2.10 (m, 2H, CH 2 ), 1.55-1.40 (m, 3H, CH 3  and CH 2 ), 0.92 and 0.86 (t,  3 J HH =6.8 Hz, 3H, CH 3 ); HRMS (ESI) calcd for C 17 H 23 N 4 O[M+H] +  299.1866. found 299.1870. 
       (1S,3S)—N′-octadien-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -24) 
       [0259]    Yellow solid, yield 78%, melting point 68-71° C.; 
         [0260]      1 H NMR (400 MHz, CDCl 3 ) δ 9.94 and 9.02 (s, 1H, NH), 7.90 and 7.50 (s, 1H, N═CH), 7.50 and 7.46 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.34 and 7.32 (d,  3 J HH =8.4 Hz, 1H, Ar—H), 7.17 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 7.11 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.53 and 3.76 (dd,  3 J HH =11.2 Hz, 4.4 Hz, 1H, CH), 4.33-4.17 (m, 1H, CH), 3.37 and 3.13 (dd,  3 J HH =2.8 Hz,  3 J HH =14.4 Hz, 1H, CH 2 ), 2.83-2.72 (m, 1H, CH 2 ), 2.38 and 2.22 (q,  3 J HH =7.2 Hz, 2H, CH 2 ), 1.96 (br, 1H, NH), 1.58-1.43 (m, 3H, CH 3  and CH 3 ), 1.42-1.18 (m, 9H, CH 2 ), 0.95-0.81 (m, 3H, CH 3 ); HRMS (ESI) calcd for C 21 H 35 N 4 O[M+H] +  355.2493. found 355.2492. 
       (1S,3S)—N′-(cyclohexylmethylene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -25) 
       [0261]    Yellow solid, yield 92%, melting point 123-126° C.; 
         [0262]      1 H NMR (400 MHz, CDCl 3 ) δ 9.88 and 9.21 (s, 1H, NH), 7.98 and 7.96 (s, 1H, N═CH), 7.49 and 7.47 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.38-7.29 and 7.05 (m, 2H, Ar—H and O═C—NH), 7.16 and 7.16 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 7.10 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.52 and 3.66 (dd,  2 J HH =10.8 Hz, 4.4 Hz, 1H, CH), 4.28 and 4.18 (q,  3 J HH =6.8 Hz, 1H, CH), 3.35 and 3.12 (dd,  3 J HH =2.8 Hz,  3 J HH =15.6 Hz, 1H, CH 2 ), 2.85-2.72 (m, 1H, CH 2 ), 2.47-2.35 and 2.23-2.13 (m, 1H, CH), 1.94 (br, 1H, NH), 1.87-1.58 (m, 4H, CH 3 ), 1.53 and 1.48 (d,  3 J HH =10.8 Hz, 3H, CH 3 ), 1.38-1.11 (m, 6H, CH 2 ), 0.95-0.81 (m, 3H, CH 3 ); HRMS (ESI) calcd for C 20 H 27 N 4 O[M+H] +  339.2180. found 339.2179. 
       (1S,3S)—N′-(2, 2-dimethylpropylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -26) 
       [0263]    Yellow solid, yield 95%, melting point 140-141° C.; 
         [0264]      1 H NMR (400 MHz, CDCl 3 ) δ 9.93 and 9.39 (s, 1H, NH), 8.13 and 8.09 (s, 1H, N═CH), 7.53-7.02 (m, 4H, Ar—H), 4.51 and 3.67 (d,  3 J HH =8.4 Hz, 1H, CH), 4.37-4.16 (m, 1H, CH), 3.33 and 3.13 (d,  3 J HH =14.4 Hz, 1H, CH 2 ), 2.79 (t,  2 J HH =13.2 Hz, 1H, CH 2 ), 2.09 (br, 1H, NH), 1.58-1.41 (m, 3H, CH 3 ), 1.15 and 1.66 (s, 9H, CH 3 ); HRMS (ESI) calcd for C 18 H 25 N 4 O[M+H] +  313.2023. found 313.2028. 
       (1S,3S)—N′-(1-phenylethylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -27) 
       [0265]    Light yellow solid, yield 56%, melting point 221-224° C.; 
         [0266]      1 H NMR (400 MHz, DMSO-d 6 ) δ 10.84 and 10.81 (s, 1H, N—H), 10.69 and 10.48 (s, 1H, O═C—NH), 7.89-7.77 and 7.76-7.67 (m, 2H, Ph-H), 7.48-7.27 (m, 5H, Ph-H and Ar—H), 7.08-6.88 (m, 2H, Ar—H), 4.53 and 3.78 (dd,  3 J HH =10.8 Hz, 3.6 Hz, 1H, CH), 4.23-4.11 (m, 1H, CH), 3.03-2.93 (m, 1H, CH 2 ), 2.76-2.59 (m, 1H, CH 2 ), 3.31 and 3.30 (s, 3H, CH 3 ), 1.46 (d,  3 J HH =6.4 Hz, 3H, CH 3 ); HRMS (ESI) calcd for C 23 H 22 N 4 O[M+H] +  347.1867. found 347.1872. 
       (1S,3S)—N′-(3, 3-dimethyl-2-butylidene)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -28) 
       [0267]    Yellow solid, yield 63%, melting point 103-107° C.; 
         [0268]      1 H NMR (400 MHz, DMSO-d 6 ) δ 10.80 and 10.79 (s, 1H, N—H), 10.18 and 10.02 (s, 1H, O═C—NH), 7.40 and 7.35 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.29 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.03 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 6.95 and 6.93 (t,  3 J HH =6.8 Hz, 1H, Ar—H), 4.26 and 3.65 (dd,  3 J HH =10.8 Hz, 4.0 Hz, 1H, CH), 4.16-4.07 (m, 1H, CH), 2.94 (dd,  3 J HH =2.8 Hz,  3 J HH =14.8 Hz, 1H, CH 2 ), 2.70-2.53 (m, 1H, CH 2 ), 1.87 and 1.85 (s, 3H, CH 3 ), 1.43 (d,  3 J HH =6.4 Hz, 3H, CH 3 ), 1.12 and 1.04 (s, 9H, CH 3 ); HRMS (ESI) calcd for C 26 H 23 N 2 O[M+H] +  327.2180. found 327.2186. 
       (1S,3S)—N′-cyclohexylidene-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I c -29) 
       [0269]    Yellow solid, yield 60%, melting point 131-135° C.; 
         [0270]      1 H NMR (400 MHz, DMSO-d 6 ) δ 10.81 and 10.78 (s, 1H, NH), 10.39 and 10.24 (s, 1H, O═C—NH), 7.39 and 7.36 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.29 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.02 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 6.94 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.36 and 3.62 (dd,  3 J HH =10.0 Hz, 3.6 Hz, 1H, CH), 4.18-4.04 (m, 1H, CH), 2.94-2.84 (m, 1H, CH 2 ), 2.69-2.58 (m, 1H, CH 2 ), 2.40-2.12 (m, 4H, CH 2 ), 1.71-1.51 (m, 6H, CH 2 ), 1.42 (d,  3 J HH =6.0 Hz, 3H, CH 3 ); HRMS (ESI) calcd for C 19 H 25 N 4 O[M+H] +  325.2023. found 325.2023. 
       Embodiment 20 
     N′-((1S,3S)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-tricarboxylate)benzo[d][1,2,3]thiadiazole-7-formylhydrazine (I d -1) 
       [0271]    
       
                 
         
             
             
         
       
     
         [0272]    Add 0.40 g (1.64 mmol) of hydrazide and 40 mL of tetrahydrofuran to a 100 mL single-necked flask, add 0.22 g (2.17 mmol) of NEt 3 , add a tetrahydrofuran solution containing acyl chloride (1.64 mmol), stir them at room temperature overnight after dropwise addition and remove the solvent to obtain 0.48 g of green solid. The yield is 72% and the melting point is 180-183° C.;  1 H NMR (400 MHz, DMSO-d 6 ) δ 11.22 (br, 1H, O═C—NH), 10.91 (s, 1H, NH), 10.37 (br, 1H, O═C‥NH), 9.00 (d,  3 J HH =8.0 Hz, 1H, Ph-H), 8.62 (d,  3 J HH =7.2 Hz, 1H, Ph-H), 7.99 (t,  3 J HH =7.6 Hz, 1H, Ph-H), 7.44 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.33 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.06 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 6.99 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.40-4.20 (m, 1H, CH), 3.97-3.76 (m, 1H, CH), 3.11-2.99 (m, 1H, CH 2 ), 2.85-2.73 (m, 1H, CH 2 ), 1.50 (d,  3 J HH =6.0 Hz, 3H, CH 3 ); HRMS (ESI) calcd for C 20 H 33 N 6 O 2 S[M+H] +  407.1285. found 407.1281. 
         [0273]    Compounds I d -2-I d -7 are completed through repeating the foregoing steps 
       4-methyl-N′-((1S,3S)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-triformyl)-1,2,3-thiadiazole-5-formylhydrazine (I d -2) 
       [0274]    Green solid, yield 56%, melting point 145-148° C.; 
         [0275]      1 H NMR (400 MHz, DMSO-d 6 ) δ 10.85 (s, 1H, NH), 10.29 (br, 1H, O═C—NH), 7.40 (d,  3 J HH =7.2 Hz, 1H, Ar—H), 7.31 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.04 (t,  3 J HH =6.8 Hz, 1H, Ar—H), 6.97 (t,  3 J HH =6.8 Hz, 1H, Ar—H), 4.25-4.11 (m, 1H, CH), 3.78-3.62 (m, 1H, CH), 3.03-2.92 (m, 1H, CH 2 ), 2.85 (s, 3H, CH 3 ), 2.78-2.64 (m, 1H, CH 2 ), 1.46 (d,  3 J HH =5.2 Hz, 3H, CH 3 ); HRMS (ESI) calcd for C 13 H 15 N 6 O 2 S[M+H] +  371.1285. found 371.1287. 
       (1S,3S)—N′-isonicotinoyl-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I d -3) 
       [0276]    Brown solid, yield 23%, melting point 243-245° C.; 
         [0277]      1 H NMR (400 MHz, DMSO-d 6 ) δ 10.81 (s, 2H, NH and O═C—NH), 10.14 (br, 1H, O═C—NH), 8.78 (d,  3 J HH =4.0 Hz, 2H, Py-H), 7.81 (d,  3 J HH =4.0 Hz, 2H, Py-H), 7.39 (d,  3 J HH =7.2 Hz, 1H, Ar—H), 7.30 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.04 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 6.96 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.18-4.08 (m, 1H, CH), 3.68-3.59 (m, 1H, CH), 2.98-2.88 (m, 1H, CH 3 ), 2.76-2.64 (m, 1H, CH 3 ), 1.44 (d,  3 J HH =6.4 Hz, 3H, CH 3 ); HRMS (ESI) calcd for C 15 H 20 N 5 O 3 [M+H] +  350.1612. found 350.1606. 
       (1S,3S)—N′-benzoyl-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I d -4) 
       [0278]    yellow solid, yield 93%, melting point 140-143° C.; 
         [0279]      1 H NMR (400 MHz, DMSO-d 6 ) δ 10.83 (s, 1H, NH), 10.47 (br, 1H, O═C—NH), 10.02 (br, 1H, and O═C—NH), 7.92 (d,  3 J HH =7.2 Hz, 2H, Ph-H), 7.60 (t,  3 J HH =7.2 Hz, 1H, Ph-H), 7.52 (t,  3 J HH =7.2 Hz, 2H, Ph-H), 7.40 (d,  3 J HH =7.2 Hz, 1H, Ar—H), 7.31 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.04 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 6.97 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.20-4.11 (m, 1H, CH), 3.66 (dd,  3 J HH =10.0 Hz, 3.2 Hz, 1H, CH), 2.95 (dd,  3 J HH =2.8 Hz,  3 J HH =14.4 Hz, 1H, CH 2 ), 2.75-2.65 (m, 1H, CH 2 ), 1.45 (d,  3 J HH =6.8 Hz, 3H, CH 3 ); HRMS (ESI) calcd for C 30 H 21 N 4 O 2 [M+H] +  349.1659. found 349.1665. 
       (1S,3S)—N′—N-Hexanoyl-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I d -5) 
       [0280]    Light yellow solid, yield 78%, melting point 97-100° C.; 
         [0281]      1 H NMR (400 MHz, DMSO-d 6 ) δ 10.79 (s, 1H, NH), 9.87 (s, 1H, O═C—NH), 9.81 (br, 1H, O═C—NH), 7.37 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.29 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.03 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 6.95 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.15-4.03 (m, 1H, CH), 3.55 (dd,  3 J HH =10.4 Hz, 3.6 Hz, 1H, CH), 2.87 (dd,  3 J HH =2.4 Hz,  2 J HH =14.8 Hz, 1H, CH 2 ), 2.62 (ddd,  3 J HH =2.0 Hz,  3 J HH =10.8 Hz,  2 J HH =14.8 Hz, 1H, CH 2 ), 2.15 (t,  3 J HH =7.2 Hz, 2H, CH 2 ), 1.60-1.48 (m, 2H, CH 2 ), 1.42 (d,  3 J HH =6.8 Hz, 3H, CH 3 ), 1.24-1.21 (m, 4H, CH 2 CH 2 ), 6.88 (t,  3 J HH =6.8 Hz, 2H, CH 2 ); HRMS (ESI) calcd for C 19 H 27 N 8 O 2 [M+H] +  343.2129. found 343.2132. 
       (1S,3S)—N′-tert-valeryl-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I d -6) 
       [0282]    Yellow solid, yield 93%, melting point 124-126° C.; 
         [0283]      1 H NMR (400 MHz, CDCl 3 ) δ 8.83 (br, 1H, O═C—NH), 8.34 (s, 1H, O═C—NH), 7.25 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.15 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.00 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 6.93 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 3.95-3.81 (m, 1H, CH), 3.49 (dd,  3 J HH =10.8 Hz, 1H, CH), 3.05-2.97 (m, 1H, CH 2 ), 2.63-2.50 (m, 1H, CH 2 ), 1.30-1.07 (m, 12H, CH 3 ); HRMS (ESI) calcd for C 18 H 25 N 6 O 2 [M+H] +  329.1972. found 429.1975. 
       (1S,3S)—N′-(cyclopentyl formyl)-1-methyl-2,3,4,9-tetrahydropyridino[3,4-b]indol-3-formylhydrazine (I d -7) 
       [0284]    White solid, yield 80%, melting point 141-144° C.; 
         [0285]      1 H NMR (400 MHz, DMSO-d 6 ) δ 10.83 (s, 1H, NH), 9.94-9.74 (m, 2H, O═C—NH), 7.37 (d,  3 J HH =7.6 Hz, 1H, Ar—H), 7.30 (d,  3 J HH =8.0 Hz, 1H, Ar—H), 7.03 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 6.96 (t,  3 J HH =7.2 Hz, 1H, Ar—H), 4.19-4.06 (m, 1H, CH), 3.66-3.54 (m, 1H, CH), 2.96-2.84 (m, 1H, CH 2 ), 2.72-2.57 (m, 2H, CH 2  and cyclopentyl-CH), 1.85-1.48 (m, 8H, cyclopentyl-CH 2 ), 1.43 (d,  3 J HH =6.4 Hz, 3H, CH 3 ); HRMS (ESI) calcd for C 19 H 25 N 8 O 2 [M+H] +  341.1972. found 341.1968. 
       Embodiment 21 
     Determination of Activity Against Tobacco Mosaic Virus, and the Determination Procedure is as Follows 
       [0286]    1. Virus Purification and Concentration Determination: 
         [0287]    Virus purification and concentration determination are executed by referring to the SOP for tobacco mosaic virus formulated by Bioassay Laboratory of the Research Institute of Elmento-organic Chemistry at Nankai University. After the crude extract of virus undergoes centrifugal treatment of polyethylene glycol twice, its concentration is determined. It is kept at 4° C. for future use. 
         [0288]    2. Preparation of a Compound Solution: 
         [0289]    After weighing, DMF is added to dissolve the crude drug and obtain a 1×10 5  m/mL mother solution. Then it is diluted with a 1%0 Tween 80 aqueous solution to the needed concentration; water is added to ningnanmycin formulation for dilution. 
         [0290]    3. In Vitro Effect: 
         [0291]    Mechanically inoculate the leaves of  Nicotiana tabacum  L.cv.Xanthi NN at an appropriate age and wash them with water (virus concentration is 10 m/mL). Cut them off after water drains, halves each leaf along the midrib, soak the left half leaf and the right half leaf in 1%0 Tween water and drug respectively, take them out 30 min later, and culture them at appropriate illumination and temperature in a moist state. Use 3 leaves each time and repeat the test 3 times. Record the number of necrotic lesions and calculate the preventive effect 3d later. 
         [0292]    4. In Vivo Protective Effect: 
         [0293]    Select evenly growing  Nicotiana tabacum  L.cv.Xanthi NN in 3-5-leaf stage, spray drug to the whole plants, repeat the treatment 3 times, and use 1%0 Tween 80 aqueous solution as control. Sprinkle emery (50 mesh) on leaf surface 24 h later, dip virus solution by a writing brush, smear the solution on the whole leaves along the direction of branch veins twice, hold up the leaves with palm under them (virus concentration is 10 μg/mL) and wash the leaves with running water after inoculation. Record the number of necrotic lesions and calculate the preventive effect 3d later. 
         [0294]    5. In Vivo Therapeutic Effect: 
         [0295]    Select evenly growing  Nicotiana tabacum  L.cv.Xanthi NN in 3-5-leaft stage, inoculate the virus to whole leaves by a writing brush (virus concentration is 10 μg/mL), and wash the leaves with running water after inoculation. Spray drug to the whole plants after the water on leaf surface drains, repeat the treatment for 3 times, and use 1%0 Tween 80 aqueous solution as control. Record the number of necrotic lesions and calculate the preventive effect 3d later. 
         [0296]    6. In Vivo Inactivation: 
         [0297]    Select evenly growing  Nicotiana tabacum  L.cv.Xanthi NN in 3-5-leaft stage, mix the drug with virus juice in an equal volume for inactivation, mechanically inoculate it 30 min later (virus concentration is 20 μg/mL), wash with running water after inoculation, repeat the treatment for 3 times, and use 1%0 Tween 80 aqueous solution as control. Record the number of necrotic lesions and calculate the result 3d later. 
         [0000]      Inhibition rate (%)=[(number of necrotic lesions in the control group-number of necrotic lesions in the treatment group)/number of necrotic lesions in the control group]×100%
 
         [0000]    
       
         
               
             
               
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Test results of anti-TMV activity of some of β-carboline, 
               
               
                 dihydro-β-carboline and tetrahydro-β-carboline alkaloids and 
               
               
                 their derivatives (I a , I b , I c  and I d ): 
               
             
          
           
               
                   
                 Relative inhibition rate (%) 
               
             
          
           
               
                   
                 Treatment 
                   
                 In vivo 
                   
                   
               
               
                   
                 dose  
                 In vitro 
                 inacti- 
                 In vivo 
                 In vivo 
               
               
                 No. 
                 (μg/mL) 
                 activity 
                 vation 
                 therapy 
                 protection 
               
               
                   
               
             
          
           
               
                 Harmalan 
                 500 
                 58.6 
                 62.3 
                 55.1 
                 60.3 
               
               
                   
                 100 
                 30 
                 32.7 
                 34.8 
                 35.6 
               
               
                 Tetrahydroharmane 
                 500 
                 63.7 
                 64.2 
                 57.2 
                 59.5 
               
               
                   
                 100 
                 28.4 
                 23.5 
                 20.4 
                 24.6 
               
               
                 Harmane 
                 500 
                 54.3 
                 50.6 
                 50 
                 57.8 
               
               
                   
                 100 
                 16.4 
                 17.7 
                 23.7 
                 26.9 
               
               
                 Tetrahydroharmine 
                 500 
                 58.2 
                 59.8 
                 55.5 
                 54.6 
               
               
                   
                 100 
                 28.7 
                 26.4 
                 27.3 
                 24.2 
               
               
                 Harmine 
                 500 
                 44.6 
                 40.5 
                 38.6 
                 42.4 
               
               
                   
                 100 
                 20 
                 11.4 
                 15.8 
                 16.3 
               
               
                 Harmol 
                 500 
                 32.6 
                 35.1 
                 30 
                 36.7 
               
               
                   
                 100 
                 0 
                 0 
                 0 
                 9.5 
               
               
                 I a -1 
                 500 
                 44.5 
                 46.3 
                 47.4 
                 51.2 
               
               
                   
                 100 
                 18.2 
                 14.9 
                 19.3 
                 20.4 
               
               
                 I a -3 
                 500 
                 15.7 
                 21.5 
                 18.5 
                 26.1 
               
               
                   
                 100 
                 0 
                 0 
                 0 
                 0 
               
               
                 I a -4 
                 500 
                 30 
                 36.4 
                 33.3 
                 30.1 
               
               
                   
                 100 
                 0 
                 10.5 
                 0 
                 5.8 
               
               
                 I a -5 
                 500 
                 31.3 
                 29.5 
                 32.7 
                 40.3 
               
               
                   
                 100 
                 0 
                 0 
                 0 
                 5.8 
               
               
                 I a -6 
                 500 
                 12.6 
                 12 
                 15.6 
                 18.7 
               
               
                   
                 100 
                 0 
                 0 
                 0 
                 0 
               
               
                 I a -7 
                 500 
                 30 
                 20.3 
                 24.1 
                 27.2 
               
               
                   
                 100 
                 0 
                 0 
                 0 
                 0 
               
               
                 I a -8 
                 500 
                 0 
                 15.3 
                 0 
                 14.4 
               
               
                   
                 100 
                 0 
                 0 
                 0 
                 0 
               
               
                 I a -9 
                 500 
                 20.7 
                 13.6 
                 12.5 
                 19.6 
               
               
                   
                 100 
                 0 
                 0 
                 0 
                 0 
               
               
                 I a -10 
                 500 
                 33.3 
                 26.3 
                 28.8 
                 23.7 
               
               
                   
                 100 
                 0 
                 0 
                 0 
                 0 
               
               
                 I a -11 
                 500 
                 32.5 
                 27.3 
                 29.6 
                 21.4 
               
               
                   
                 100 
                 0 
                 0 
                 0 
                 0 
               
               
                 I a -14 
                 500 
                 25.8 
                 18.4 
                 21.5 
                 28.4 
               
               
                   
                 100 
                 0 
                 0 
                 0 
                 0 
               
               
                 I a -15 
                 500 
                 40.2 
                 39.6 
                 36.2 
                 35.1 
               
               
                   
                 100 
                 0 
                 13.5 
                 10 
                 10.2 
               
               
                 I a -16 
                 500 
                 17.8 
                 26.5 
                 20.2 
                 21.3 
               
               
                   
                 100 
                 0 
                 0 
                 0 
                 0 
               
               
                 I b -1 
                 500 
                 41.6 
                 35.5 
                 40.4 
                 41.3 
               
               
                   
                 100 
                 18.9 
                 13.5 
                 15.8 
                 20 
               
               
                 I b -2 
                 500 
                 25 
                 28.6 
                 31.5 
                 29.7 
               
               
                   
                 100 
                 0 
                 0 
                 0 
                 0 
               
               
                 I b -5 
                 500 
                 19.7 
                 27.6 
                 24.3 
                 32.3 
               
               
                   
                 100 
                 0 
                 0 
                 0 
                 0 
               
               
                 I b -6 
                 500 
                 25 
                 17.5 
                 21.4 
                 24.8 
               
               
                   
                 100 
                 0 
                 0 
                 0 
                 0 
               
               
                 I b -7 
                 500 
                 26.9 
                 36.5 
                 30.7 
                 40.1 
               
               
                   
                 100 
                 12.3 
                 19.3 
                 15.9 
                 16.2 
               
               
                 I b -8 
                 500 
                 48.2 
                 51.3 
                 42.2 
                 43.2 
               
               
                   
                 100 
                 13.4 
                 20.3 
                 17.1 
                 17.6 
               
               
                 I b -9 
                 500 
                 44.5 
                 41 
                 42.7 
                 40.4 
               
               
                   
                 100 
                 12.8 
                 16.9 
                 14.3 
                 17.2 
               
               
                 I b -10 
                 500 
                 34.1 
                 46.4 
                 38.1 
                 36.6 
               
               
                   
                 100 
                 0 
                 12.6 
                 11.4 
                 10.7 
               
               
                 I b -11 
                 500 
                 40.9 
                 37 
                 38.9 
                 36.7 
               
               
                   
                 100 
                 0 
                 13.1 
                 18 
                 14.3 
               
               
                 I b -12 
                 500 
                 40 
                 35.8 
                 38.6 
                 41.9 
               
               
                   
                 100 
                 12.6 
                 16.7 
                 12.9 
                 17 
               
               
                 I b -13 
                 500 
                 46.5 
                 50.4 
                 43.9 
                 47.9 
               
               
                   
                 100 
                 21.8 
                 25.7 
                 17.5 
                 18.6 
               
               
                 I b -14 
                 500 
                 42.6 
                 35.7 
                 45.8 
                 47 
               
               
                   
                 100 
                 11.1 
                 0 
                 15.9 
                 21.4 
               
               
                 I b -15 
                 500 
                 50 
                 46 
                 48.2 
                 49.6 
               
               
                   
                 100 
                 21.4 
                 16.5 
                 20.3 
                 23.4 
               
               
                 I b -16 
                 500 
                 38.4 
                 44 
                 44.9 
                 42.1 
               
               
                   
                 100 
                 0 
                 13.5 
                 21.1 
                 15.8 
               
               
                 I b -17 
                 500 
                 38.8 
                 43.3 
                 44.6 
                 37.1 
               
               
                   
                 100 
                 0 
                 12.3 
                 15.1 
                 14.2 
               
               
                 I b -18 
                 500 
                 37.6 
                 41.5 
                 40 
                 41 
               
               
                   
                 100 
                 5.4 
                 10 
                 18.6 
                 12.1 
               
               
                 I b -19 
                 500 
                 26.6 
                 18.5 
                 20.9 
                 24.7 
               
               
                   
                 100 
                 0 
                 0 
                 0 
                 0 
               
               
                 I b -20 
                 500 
                 37.5 
                 39.1 
                 34.2 
                 29.6 
               
               
                   
                 100 
                 0 
                 9.8 
                 0 
                 0 
               
               
                 I c -1 
                 500 
                 55.8 
                 56.3 
                 51.5 
                 53.2 
               
               
                   
                 100 
                 28.4 
                 19.6 
                 16 
                 21.8 
               
               
                 I c -2 
                 500 
                 52.4 
                 50.3 
                 47 
                 53.8 
               
               
                   
                 100 
                 17.6 
                 13.3 
                 18.2 
                 21.7 
               
               
                 I c -3 
                 500 
                 56.8 
                 64.5 
                 60.4 
                 62.4 
               
               
                   
                 100 
                 20.4 
                 25 
                 23.1 
                 18.9 
               
               
                 I c -4 
                 500 
                 62.8 
                 58.3 
                 57.1 
                 61.5 
               
               
                   
                 100 
                 19.6 
                 27.4 
                 20.8 
                 21.4 
               
               
                 I c -5 
                 500 
                 67.3 
                 70.4 
                 71.5 
                 64.2 
               
               
                   
                 100 
                 30.8 
                 35.9 
                 29.2 
                 34.1 
               
               
                 I c -6 
                 500 
                 56.8 
                 66.7 
                 60.4 
                 57.2 
               
               
                   
                 100 
                 20.1 
                 28.5 
                 31.5 
                 18.6 
               
               
                 I c -7 
                 500 
                 50.7 
                 55.2 
                 48.9 
                 48.1 
               
               
                   
                 100 
                 15.1 
                 20.4 
                 23.5 
                 14.8 
               
               
                 I c -8 
                 500 
                 62.5 
                 69.1 
                 66.4 
                 70 
               
               
                   
                 100 
                 28.7 
                 30.4 
                 34.8 
                 31.8 
               
               
                 I c -9 
                 500 
                 53.2 
                 59.2 
                 54 
                 54.7 
               
               
                   
                 100 
                 13.2 
                 22.1 
                 16.5 
                 20.6 
               
               
                 I c -10 
                 500 
                 38.5 
                 43.2 
                 36.4 
                 34.8 
               
               
                   
                 100 
                 0 
                 0 
                 10.9 
                 0 
               
               
                 I c -11 
                 500 
                 37.2 
                 47.1 
                 40.5 
                 42.3 
               
               
                   
                 100 
                 7.8 
                 20.3 
                 16.2 
                 11 
               
               
                 I c -12 
                 500 
                 72.6 
                 74.5 
                 69 
                 68.1 
               
               
                   
                 100 
                 29.1 
                 33.6 
                 30.2 
                 35.8 
               
               
                 I c -13 
                 500 
                 46.5 
                 43.6 
                 48.1 
                 46 
               
               
                   
                 100 
                 19.8 
                 15.2 
                 18.6 
                 10.3 
               
               
                 I c -14 
                 500 
                 40.9 
                 45.6 
                 43.9 
                 47.8 
               
               
                   
                 100 
                 0 
                 16.9 
                 8.2 
                 0 
               
               
                 I c -15 
                 500 
                 36.6 
                 43.4 
                 39.6 
                 37.5 
               
               
                   
                 100 
                 0 
                 8.8 
                 12.9 
                 0 
               
               
                 I c -16 
                 500 
                 33.3 
                 41 
                 36.9 
                 33.6 
               
               
                   
                 100 
                 0 
                 11.2 
                 5.7 
                 0 
               
               
                 I c -17 
                 500 
                 32.7 
                 38.9 
                 36.8 
                 31.4 
               
               
                   
                 100 
                 0 
                 9.2 
                 0 
                 0 
               
               
                 I c -18 
                 500 
                 48.8 
                 54.6 
                 44.2 
                 47.5 
               
               
                   
                 100 
                 15.4 
                 18.2 
                 9.3 
                 11.5 
               
               
                 I c -19 
                 500 
                 49.5 
                 61.3 
                 63.4 
                 54.7 
               
               
                   
                 100 
                 8.8 
                 20.2 
                 27.8 
                 30 
               
               
                 I c -20 
                 500 
                 58.5 
                 59.1 
                 52.3 
                 61.3 
               
               
                   
                 100 
                 23 
                 29.6 
                 25.1 
                 31.8 
               
               
                 I c -21 
                 500 
                 42.4 
                 49.6 
                 45.3 
                 48.1 
               
               
                   
                 100 
                 0 
                 21.3 
                 12.6 
                 18.5 
               
               
                 I c -22 
                 500 
                 35.2 
                 47 
                 33.2 
                 37.1 
               
               
                   
                 100 
                 0 
                 8.5 
                 0 
                 6.7 
               
               
                 I c -23 
                 500 
                 32.6 
                 47.1 
                 41.3 
                 40.5 
               
               
                   
                 100 
                 7.8 
                 13.4 
                 10.4 
                 11.3 
               
               
                 I c -24 
                 500 
                 61.3 
                 73.4 
                 70.9 
                 59.6 
               
               
                   
                 100 
                 23.2 
                 32.8 
                 31.7 
                 27.3 
               
               
                 I c -25 
                 500 
                 59.6 
                 75.8 
                 62.8 
                 69.2 
               
               
                   
                 100 
                 31.2 
                 36.3 
                 30.4 
                 25.7 
               
               
                 I c -26 
                 500 
                 64.4 
                 63.7 
                 68.2 
                 66.8 
               
               
                   
                 100 
                 27.5 
                 28.9 
                 36.8 
                 33.4 
               
               
                 I c -27 
                 500 
                 30.2 
                 39.5 
                 34.8 
                 37.2 
               
               
                   
                 100 
                 9.2 
                 13.6 
                 11.1 
                 7.9 
               
               
                 I c -28 
                 500 
                 58.1 
                 59.7 
                 55.4 
                 56.8 
               
               
                   
                 100 
                 25.6 
                 21.3 
                 16.7 
                 18.9 
               
               
                 I c -29 
                 500 
                 43.4 
                 33 
                 41.9 
                 46.2 
               
               
                   
                 100 
                 8.6 
                 12.8 
                 10.9 
                 14.3 
               
               
                 I d -1 
                 500 
                 52.1 
                 44.1 
                 54.5 
                 58.3 
               
               
                   
                 100 
                 22.6 
                 16.2 
                 26.8 
                 29.9 
               
               
                 I d -2 
                 500 
                 41.2 
                 42.9 
                 48.8 
                 51.3 
               
               
                   
                 100 
                 13.5 
                 9.8 
                 19.1 
                 16 
               
               
                 I d -3 
                 500 
                 39.2 
                 45.3 
                 45 
                 42.1 
               
               
                   
                 100 
                 6.4 
                 17.9 
                 11.6 
                 14.2 
               
               
                 I d -4 
                 500 
                 36.9 
                 37.5 
                 34.2 
                 40 
               
               
                   
                 100 
                 0 
                 0 
                 0 
                 12.1 
               
               
                 I d -5 
                 500 
                 32.1 
                 31.5 
                 27.3 
                 30.9 
               
               
                   
                 100 
                 0 
                 0 
                 0 
                 0 
               
               
                 I d -6 
                 500 
                 45.7 
                 44 
                 42.1 
                 47.5 
               
               
                   
                 100 
                 8.9 
                 12.8 
                 14.2 
                 16.9 
               
               
                 I d -7 
                 500 
                 47.2 
                 42.4 
                 51.4 
                 53.9 
               
               
                   
                 100 
                 22.2 
                 20.3 
                 18.6 
                 26.6 
               
               
                 NK-007 
                 500 
                 65.4 
                 65.2 
                 67.2 
                 67.9 
               
               
                   
                 100 
                 38.7 
                 33.9 
                 34.9 
                 36.2 
               
               
                 Virazole 
                 500 
                 39.5 
                 36.3 
                 35.4 
                 37.6 
               
               
                   
                 100 
                 15.3 
                 12.9 
                 11.9 
                 16.2 
               
               
                 Ningnanmycin 
                 500 
                 73.3 
                 68 
                 54.2 
                 65.4 
               
               
                   
                 100 
                 26.8 
                 38.4 
                 20 
                 23.1 
               
               
                   
               
             
          
         
       
     
         [0298]    Table 1 indicates most of β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloids and their derivatives (I a , I b , I c  and I d ) show very high in vitro anti-TMV activity, most of the compounds show very good in vivo activity against tobacco mosaic virus (TMV), and most of alkaloid and acylhydrazone compounds obviously outperform commercial variety virazole in anti-TMV in vivo activity. Particularly, the anti-TMV activity of compounds Harmalan, Tetrahydroharmane, Harmane, Tetrahydroharmine, I a -1, I b -8, I b -15, I c -1-I c -9, I c -12, I c -19, I c -20, I c -24-I c -26, I c -28, I d -1, I d -6 and I d -7 at 100 μg/mL is equivalent to the activity of commercial variety ningnanmycin at 100 μg/mL, and they have great development value. 
       Embodiment 22 
     Determination of Fungicidal Activity, and the Determination Procedure is as Follows 
       [0299]    In vitro test method ( Alternaria solani  is taken for example. Alternatively, other fungi may be used): Inoculate  Alternaria solani  to PDA culture medium, culture it for 7 days, prepare Φ4 cm bacteria plates from colony edge by a puncher, inoculate 50 m/mL and drug-free PDA culture media, culture them for 4 days, measure colony diameter, compare with the control group and calculate the inhibition percentage of the drug. 
         [0000]    
       
         
               
             
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 Test results of bactericidal activity of some of β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloids and their derivatives (I a , I b , I c  and I d ): 
               
             
          
           
               
                   
                 Bactericidal activity (%)/50 mg/kg 
               
             
          
           
               
                   
                 Cucumber 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 
                   fusarium 
                 
                 
                   Cercospora 
                 
                 
                   Macrophoma 
                 
                 
                   Alternaria 
                 
                 
                   Fusarium 
                 
                 
                   Fusarium 
                 
                 
                   Sclerotinia 
                 
                 
                   Phytophthora 
                 
                 
                   Rhizoctonia 
                 
                 
                   Bipolaria 
                 
                 
                   Colletotrichum 
                 
                 potato 
                 
                   Rhizoctonia 
                 
                 
                   Botrytis 
                 
               
               
                 No. 
                 wilt 
                 
                   arachidicola 
                 
                 
                   kawatsukai 
                 
                 
                   solani 
                 
                 
                   graminearumt 
                 
                 
                   fujikuroi 
                 
                 
                   scleotiorum 
                 
                 
                   capsici 
                 
                 
                   cereali 
                 
                 
                   maydis 
                 
                 
                   orbiculare 
                 
                 late blight 
                 
                   solani 
                 
                 
                   cinerea 
                 
               
               
                   
               
             
          
           
               
                 Harmalan 
                 23.1 
                 76.9 
                 2.4 
                 26.3 
                 21.4 
                 28.6 
                 19.6 
                 0.0 
                 55.3 
                 27.3 
                 25.0 
                 31.8 
                 19.7 
                 15.2 
               
               
                 Tetrahydr 
                 19.2 
                 61.5 
                 26.2 
                 26.3 
                 14.3 
                 14.3 
                 9.8 
                 0.0 
                 42.1 
                 18.2 
                 32.1 
                 18.2 
                 52.6 
                 12.1 
               
               
                 Harmane 
                 19.2 
                 92.3 
                 61.9 
                 68.4 
                 23.8 
                 35.7 
                 33.3 
                 15.6 
                 42.1 
                 36.4 
                 46.4 
                 9.1 
                 26.3 
                 12.1 
               
               
                 Tetrahydr 
                 19.2 
                 76.9 
                 14.3 
                 21.1 
                 11.9 
                 14.3 
                 19.6 
                 9.4 
                 34.2 
                 27.3 
                 25.0 
                 22.7 
                 26.3 
                 27.3 
               
               
                 Harmine 
                 28.6 
                 57.1 
                 35.3 
                 83.3 
                 92.9 
                 57.1 
                 48.0 
                 60.6 
                 71.9 
                 31.6 
                 57.1 
                 35.0 
                 21.4 
                 59.1 
               
               
                 Harmol 
                 26.9 
                 46.2 
                 23.8 
                 26.3 
                 23.8 
                 28.6 
                 5.9 
                 25.0 
                 42.1 
                 31.8 
                 46.4 
                 22.7 
                 50.0 
                 9.1 
               
               
                 I a -1 
                 65.4 
                 84.6 
                 61.9 
                 73.7 
                 76.2 
                 64.3 
                 41.2 
                 93.8 
                 68.4 
                 86.4 
                 92.9 
                 45.5 
                 96.1 
                 45.5 
               
               
                 I a -3 
                 23.8 
                 7.1 
                 35.3 
                 33.3 
                 50.0 
                 42.9 
                 56.0 
                 36.4 
                 59.4 
                 31.6 
                 23.8 
                 25.0 
                 10.7 
                 54.6 
               
               
                 I a -4 
                 38.5 
                 53.9 
                 35.7 
                 15.8 
                 42.9 
                 21.4 
                 29.4 
                 9.4 
                 50.0 
                 36.4 
                 42.9 
                 27.3 
                 42.1 
                 18.2 
               
               
                 I a -5 
                 34.6 
                 53.9 
                 2.4 
                 21.1 
                 23.8 
                 14.3 
                 9.8 
                 25.0 
                 36.8 
                 22.7 
                 39.3 
                 18.2 
                 6.6 
                 0.0 
               
               
                 I a -6 
                 23.1 
                 53.9 
                 26.2 
                 15.8 
                 38.1 
                 21.4 
                 7.8 
                 9.4 
                 36.8 
                 27.3 
                 35.7 
                 9.1 
                 46.1 
                 12.1 
               
               
                 I a -7 
                 14.3 
                 35.7 
                 5.9 
                 33.3 
                 35.7 
                 35.7 
                 76.0 
                 18.2 
                 62.5 
                 21.1 
                 33.3 
                 20.0 
                 0.0 
                 36.4 
               
               
                 I a -8 
                 52.4 
                 71.4 
                 76.5 
                 66.7 
                 78.6 
                 50.0 
                 80.0 
                 93.9 
                 90.6 
                 79.0 
                 71.4 
                 50.0 
                 42.9 
                 54.6 
               
               
                 I a -9 
                 38.5 
                 61.5 
                 78.6 
                 36.8 
                 35.7 
                 21.4 
                 13.7 
                 50.0 
                 84.2 
                 36.4 
                 50.0 
                 45.5 
                 52.6 
                 51.5 
               
               
                 I a -10 
                 23.8 
                 35.7 
                 52.9 
                 61.1 
                 71.4 
                 35.7 
                 68.0 
                 51.5 
                 78.1 
                 36.8 
                 47.6 
                 35.0 
                 39.3 
                 13.6 
               
               
                 I a -11 
                 19.1 
                 50.0 
                 82.4 
                 33.3 
                 35.7 
                 35.7 
                 72.0 
                 60.6 
                 53.1 
                 21.1 
                 38.1 
                 25.0 
                 42.9 
                 63.6 
               
               
                 I a -14 
                 23.1 
                 84.6 
                 47.6 
                 10.5 
                 14.3 
                 28.6 
                 9.8 
                 18.8 
                 63.2 
                 22.7 
                 25.0 
                 22.7 
                 39.5 
                 12.1 
               
               
                 I a -15 
                 33.3 
                 21.4 
                 58.8 
                 22.2 
                 78.6 
                 64.3 
                 76.0 
                 66.7 
                 81.3 
                 73.7 
                 66.7 
                 55.0 
                 17.9 
                 68.2 
               
               
                 I a -16 
                 4.8 
                 0.0 
                 23.5 
                 22.2 
                 42.9 
                 28.6 
                 76.0 
                 9.1 
                 53.1 
                 15.8 
                 23.8 
                 15.0 
                 0.0 
                 4.6 
               
               
                 I b -1 
                 19.2 
                 30.8 
                 23.8 
                 21.1 
                 26.2 
                 21.4 
                 7.8 
                 18.8 
                 42.1 
                 22.7 
                 35.7 
                 27.3 
                 26.3 
                 21.2 
               
               
                 I b -2 
                 23.1 
                 61.5 
                 23.8 
                 0.0 
                 21.4 
                 0.0 
                 23.5 
                 15.6 
                 31.6 
                 9.1 
                 25.0 
                 4.6 
                 29.0 
                 18.2 
               
               
                 I b -5 
                 19.2 
                 69.2 
                 11.9 
                 15.8 
                 26.2 
                 42.9 
                 9.8 
                 12.5 
                 44.7 
                 22.7 
                 35.7 
                 22.7 
                 36.8 
                 21.2 
               
               
                 I b -6 
                 26.9 
                 84.6 
                 61.9 
                 26.3 
                 31.0 
                 14.3 
                 29.4 
                 9.4 
                 63.2 
                 36.4 
                 32.1 
                 27.3 
                 32.9 
                 27.3 
               
               
                 I b -7 
                 33.3 
                 42.9 
                 64.7 
                 50.0 
                 42.9 
                 64.3 
                 60.0 
                 66.7 
                 78.1 
                 42.1 
                 47.6 
                 40.0 
                 42.9 
                 50.0 
               
               
                 I b -8 
                 33.3 
                 71.4 
                 64.7 
                 83.3 
                 50.0 
                 50.0 
                 72.0 
                 51.5 
                 84.4 
                 89.5 
                 38.1 
                 35.0 
                 55.4 
                 50.0 
               
               
                 I b -9 
                 19.2 
                 84.6 
                 21.4 
                 26.3 
                 35.7 
                 14.3 
                 19.6 
                 15.6 
                 44.7 
                 22.7 
                 42.9 
                 22.7 
                 35.5 
                 12.1 
               
               
                 I b -10 
                 23.8 
                 21.4 
                 64.7 
                 55.6 
                 35.7 
                 35.7 
                 56.0 
                 45.5 
                 65.6 
                 31.6 
                 42.9 
                 30.0 
                 21.4 
                 40.9 
               
               
                 I b -11 
                 23.8 
                 42.9 
                 35.3 
                 55.6 
                 28.6 
                 28.6 
                 76.0 
                 36.4 
                 65.6 
                 15.8 
                 42.9 
                 35.0 
                 17.9 
                 40.9 
               
               
                 I b -12 
                 19.2 
                 92.3 
                 54.8 
                 26.3 
                 26.2 
                 28.6 
                 17.7 
                 9.4 
                 39.5 
                 18.2 
                 25.0 
                 18.2 
                 42.1 
                 24.2 
               
               
                 I b -13 
                 28.6 
                 50.0 
                 29.4 
                 55.6 
                 21.4 
                 42.9 
                 68.0 
                 60.6 
                 59.4 
                 26.3 
                 38.1 
                 30.0 
                 33.9 
                 68.2 
               
               
                 I b -14 
                 23.1 
                 69.2 
                 33.3 
                 42.1 
                 42.9 
                 28.6 
                 29.4 
                 15.6 
                 65.8 
                 36.4 
                 42.9 
                 36.4 
                 59.2 
                 36.4 
               
               
                 I b -15 
                 13.6 
                 18.2 
                 39.4 
                 9.5 
                 38.5 
                 29.4 
                 30.8 
                 51.5 
                 54.1 
                 24.0 
                 24.0 
                 26.1 
                 4.2 
                 27.8 
               
               
                 I b -16 
                 23.1 
                 84.6 
                 33.3 
                 21.1 
                 14.3 
                 14.3 
                 0.0 
                 18.8 
                 57.9 
                 18.2 
                 28.6 
                 22.7 
                 46.1 
                 18.2 
               
               
                 I b -17 
                 34.6 
                 69.2 
                 47.6 
                 52.6 
                 59.5 
                 28.6 
                 33.3 
                 37.5 
                 71.1 
                 45.5 
                 50.0 
                 31.8 
                 50.0 
                 27.3 
               
               
                 I b -18 
                 23.8 
                 21.4 
                 70.6 
                 27.8 
                 28.6 
                 35.7 
                 68.0 
                 36.4 
                 53.1 
                 26.3 
                 23.8 
                 5.0 
                 35.7 
                 27.3 
               
               
                 I b -19 
                 19.2 
                 41.2 
                 55.6 
                 25.0 
                 27.6 
                 21.4 
                 35.3 
                 7.9 
                 47.1 
                 24.0 
                 25.9 
                 20.0 
                 26.3 
                 27.3 
               
               
                 I b -20 
                 15.4 
                 23.5 
                 27.8 
                 20.0 
                 24.1 
                 21.4 
                 0.0 
                 18.4 
                 47.1 
                 16.0 
                 18.5 
                 20.0 
                 13.2 
                 36.4 
               
               
                 I c -1 
                 36.4 
                 72.7 
                 36.4 
                 57.1 
                 53.8 
                 58.8 
                 26.9 
                 69.7 
                 86.5 
                 60.0 
                 52.0 
                 30.4 
                 48.6 
                 88.9 
               
               
                 I c -2 
                 65.4 
                 82.4 
                 97.2 
                 70.0 
                 41.4 
                 57.1 
                 94.1 
                 73.7 
                 98.0 
                 84.0 
                 77.8 
                 76.0 
                 88.2 
                 86.4 
               
               
                 I c -3 
                 38.5 
                 76.5 
                 97.2 
                 65.0 
                 31.0 
                 35.7 
                 41.2 
                 78.9 
                 96.1 
                 64.0 
                 48.1 
                 72.0 
                 63.2 
                 72.7 
               
               
                 I c -4 
                 38.5 
                 58.8 
                 72.2 
                 45.0 
                 58.6 
                 42.9 
                 88.2 
                 78.9 
                 88.2 
                 60.0 
                 48.1 
                 52.0 
                 59.2 
                 72.7 
               
               
                 I c -5 
                 61.5 
                 76.5 
                 97.2 
                 55.0 
                 75.9 
                 64.3 
                 88.2 
                 81.6 
                 94.1 
                 68.0 
                 77.8 
                 80.0 
                 81.6 
                 59.1 
               
               
                 I c -6 
                 27.3 
                 45.5 
                 48.5 
                 42.9 
                 53.8 
                 47.1 
                 46.2 
                 60.6 
                 56.8 
                 56.0 
                 60.0 
                 39.1 
                 45.8 
                 52.8 
               
               
                 I c -7 
                 77.3 
                 72.7 
                 97.0 
                 71.4 
                 76.9 
                 70.6 
                 84.6 
                 84.8 
                 97.3 
                 80.0 
                 80.0 
                 65.2 
                 62.5 
                 80.6 
               
               
                 I c -8 
                 23.1 
                 64.7 
                 72.2 
                 30.0 
                 65.5 
                 64.3 
                 94.1 
                 73.7 
                 84.3 
                 68.0 
                 55.6 
                 52.0 
                 59.2 
                 59.1 
               
               
                 I c -9 
                 34.6 
                 58.8 
                 69.4 
                 65.0 
                 41.4 
                 57.1 
                 88.2 
                 81.6 
                 92.2 
                 48.0 
                 40.7 
                 40.0 
                 68.4 
                 68.2 
               
               
                 I c -10 
                 26.9 
                 23.5 
                 88.9 
                 45.0 
                 72.4 
                 21.4 
                 64.7 
                 63.2 
                 78.4 
                 56.0 
                 40.7 
                 44.0 
                 32.9 
                 77.3 
               
               
                 I c -11 
                 22.7 
                 45.5 
                 66.7 
                 52.4 
                 30.8 
                 47.1 
                 21.2 
                 84.8 
                 89.2 
                 52.0 
                 72.0 
                 30.4 
                 44.4 
                 66.7 
               
               
                 I c -12 
                 31.8 
                 63.6 
                 63.6 
                 52.4 
                 53.8 
                 58.8 
                 44.2 
                 81.8 
                 86.5 
                 56.0 
                 48.0 
                 39.1 
                 50.0 
                 88.9 
               
               
                 I c -13 
                 22.7 
                 45.5 
                 66.7 
                 52.4 
                 30.8 
                 47.1 
                 21.2 
                 84.8 
                 89.2 
                 52.0 
                 72.0 
                 30.4 
                 44.4 
                 66.7 
               
               
                 I c -14 
                 19.2 
                 47.1 
                 77.8 
                 30.0 
                 10.3 
                 28.6 
                 88.2 
                 84.2 
                 86.3 
                 56.0 
                 48.1 
                 44.0 
                 28.9 
                 72.7 
               
               
                 I c -15 
                 23.1 
                 35.3 
                 52.8 
                 15.0 
                 27.6 
                 21.4 
                 64.7 
                 28.9 
                 66.7 
                 28.0 
                 29.6 
                 24.0 
                 23.7 
                 36.4 
               
               
                 I c -16 
                 38.5 
                 41.2 
                 83.3 
                 15.0 
                 62.1 
                 50.0 
                 35.3 
                 26.3 
                 80.4 
                 32.0 
                 40.7 
                 52.0 
                 39.5 
                 54.5 
               
               
                 I c -17 
                 23.1 
                 23.5 
                 75.0 
                 20.0 
                 20.7 
                 21.4 
                 5.9 
                 18.4 
                 41.2 
                 16.0 
                 25.9 
                 12.0 
                 21.1 
                 36.4 
               
               
                 I c -18 
                 11.5 
                 52.9 
                 69.4 
                 35.0 
                 6.9 
                 28.6 
                 64.7 
                 39.5 
                 68.6 
                 20.0 
                 33.3 
                 36.0 
                 32.9 
                 81.8 
               
               
                 I c -19 
                 23.1 
                 23.5 
                 97.2 
                 15.0 
                 41.4 
                 14.3 
                 58.8 
                 42.1 
                 74.5 
                 28.0 
                 29.6 
                 24.0 
                 32.9 
                 22.7 
               
               
                 I c -20 
                 26.9 
                 47.1 
                 55.6 
                 45.0 
                 62.1 
                 28.6 
                 88.2 
                 68.4 
                 72.5 
                 44.0 
                 44.4 
                 36.0 
                 46.1 
                 72.7 
               
               
                 I c -21 
                 34.6 
                 47.1 
                 97.2 
                 15.0 
                 27.6 
                 28.6 
                 35.3 
                 18.4 
                 64.7 
                 12.0 
                 25.9 
                 24.0 
                 15.8 
                 36.4 
               
               
                 I c -22 
                 26.9 
                 29.4 
                 52.8 
                 30.0 
                 20.7 
                 14.3 
                 41.2 
                 31.6 
                 64.7 
                 36.0 
                 22.2 
                 32.0 
                 6.6 
                 40.9 
               
               
                 I c -23 
                 19.2 
                 17.6 
                 69.4 
                 45.0 
                 6.9 
                 0.0 
                 64.7 
                 5.3 
                 43.1 
                 12.0 
                 14.8 
                 20.0 
                 6.6 
                 9.1 
               
               
                 I c -24 
                 9.1 
                 36.4 
                 24.2 
                 19.0 
                 61.5 
                 35.3 
                 46.2 
                 18.2 
                 29.7 
                 36.0 
                 32.0 
                 17.4 
                 22.2 
                 44.4 
               
               
                 I c -25 
                 4.5 
                 0.0 
                 33.3 
                 19.0 
                 30.8 
                 41.2 
                 21.2 
                 9.1 
                 29.7 
                 36.0 
                 24.0 
                 17.4 
                 5.6 
                 66.7 
               
               
                 I c -26 
                 4.5 
                 18.2 
                 36.4 
                 19.0 
                 46.2 
                 29.4 
                 15.4 
                 12.1 
                 48.6 
                 20.0 
                 24.0 
                 17.4 
                 8.3 
                 36.1 
               
               
                 I c -27 
                 0.0 
                 36.4 
                 39.4 
                 33.3 
                 61.5 
                 29.4 
                 11.5 
                 36.4 
                 51.4 
                 36.0 
                 52.0 
                 26.1 
                 15.3 
                 69.4 
               
               
                 I c -28 
                 4.5 
                 36.4 
                 36.4 
                 14.3 
                 53.8 
                 23.5 
                 3.8 
                 18.2 
                 48.6 
                 28.0 
                 32.0 
                 30.4 
                 8.3 
                 41.7 
               
               
                 I c -29 
                 0.0 
                 18.2 
                 9.1 
                 19.0 
                 46.2 
                 29.4 
                 7.7 
                 12.1 
                 48.6 
                 32.0 
                 32.0 
                 26.1 
                 15.3 
                 52.8 
               
               
                 I d -1 
                 13.6 
                 18.2 
                 51.5 
                 19.0 
                 61.5 
                 47.1 
                 26.9 
                 27.3 
                 43.2 
                 36.0 
                 32.0 
                 17.4 
                 1.4 
                 44.4 
               
               
                 I d -2 
                 4.5 
                 18.2 
                 39.4 
                 14.3 
                 53.8 
                 29.4 
                 19.2 
                 6.1 
                 45.9 
                 28.0 
                 24.0 
                 30.4 
                 0.0 
                 61.1 
               
               
                 I d -3 
                 13.6 
                 27.3 
                 39.4 
                 14.3 
                 53.8 
                 29.4 
                 3.8 
                 15.2 
                 18.9 
                 16.0 
                 36.0 
                 26.1 
                 15.3 
                 55.6 
               
               
                 I d -4 
                 13.6 
                 27.3 
                 45.5 
                 33.3 
                 38.5 
                 29.4 
                 7.7 
                 18.2 
                 35.1 
                 28.0 
                 32.0 
                 17.4 
                 5.6 
                 55.6 
               
               
                 I d -5 
                 22.7 
                 45.5 
                 63.6 
                 23.8 
                 46.2 
                 29.4 
                 26.9 
                 21.2 
                 29.7 
                 32.0 
                 28.0 
                 26.1 
                 1.4 
                 66.7 
               
               
                 I d -6 
                 4.5 
                 9.1 
                 42.4 
                 14.3 
                 30.8 
                 29.4 
                 17.3 
                 12.1 
                 10.8 
                 20.0 
                 24.0 
                 26.1 
                 5.6 
                 50.0 
               
               
                 I d -7 
                 9.1 
                 9.1 
                 33.3 
                 9.5 
                 15.4 
                 29.4 
                 7.7 
                 15.2 
                 29.7 
                 28.0 
                 16.0 
                 21.7 
                 1.4 
                 50.0 
               
               
                 Carbendazim 
                 &lt;50 
                 &lt;50 
                 &lt;50 
                 &lt;50 
                 100 
                 &lt;50 
                 100 
                 &lt;50 
                 100 
                 100 
                 100 
                 100 
                 100 
                 &lt;50 
               
               
                 Chlorothalonil 
                 100 
                 73.3 
                 100 
                 73.3 
                 &lt;50 
                 100 
                 &lt;50 
                 100 
                 100 
                 91.3 
                 91.3 
                 86.4 
                 100 
                 100 
               
               
                   
               
             
          
         
       
     
         [0300]    Table 2 indicates most of β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloids and their derivatives (I a , I b , I c  and I d ) show high bactericidal activity against 14 kinds of fungi, and particularly, compound I a -1, I c -2, I c -5 and I c -7 show very good bactericidal activity against various kinds of fungi. 
       Embodiment 23 
     Determination of Activity Against Armyworms, Cotton Bollworms and Corn Borers. The Determination Procedure is as Follows 
       [0301]    Test of Activity Against Cotton Bollworms 
         [0302]    Experimental method of cotton bollworms: feed and drug mixing method: measure 3 mL of prepared solution and add it to about 27 g of newly prepared feed, thereby obtaining needed concentration through dilution by 10 times. Pour the evenly mixed drug into clean 24-well plates, cool it in the air, put 24 third instar cotton bollworms, observe them for 3-4 days and then check results. 
         [0303]    Test of Activity Against Armyworms 
         [0304]    Experimental method of armyworms: leaf soaking method: prepare a drug solution at the needed concentration, soak leaves with a diameter of about 5-6 cm in the drug solution for 5-6 s, take them out, put them on absorbent paper, dry them in the air, put them in a designated culture dish, put 10 third instar larvae, transfer them to a 27±1° C. insectariums, observe them for 3-4 days and then check results. 
         [0305]    Test of Activity Against Corn Borers 
         [0306]    Experimental method of corn borers: leaf soaking method: prepare a drug solution at the needed concentration, soak leaves with a diameter of about 5-6 cm in the drug solution for 5-6 s, take them out, put them on absorbent paper, dry them in the air, put them in a designated culture dish, put 10 third instar larvae, transfer them to a 27±1° C. insectariums, observe them for 3-4 days and then check results. 
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 Test results of the activity of some of β-carboline, dihydro-β-carboline and tetrahydro-β-carboline 
               
               
                 alkaloids and their derivatives (I a , I b , I c  and I d ) against armyworms, cotton bollworms and corn borers: 
               
             
          
           
               
                   
                 Armyworm 
                 Cotton bollworm 
                 Corn borer 
               
             
          
           
               
                   
                 Concentration 
                 Mortality 
                 Concentration 
                 Mortality 
                 Concentration 
                 Mortality 
               
               
                 No. 
                 (mg/kg) 
                 (%) 
                 (mg/kg) 
                 (%) 
                 (mg/kg) 
                 (%) 
               
               
                   
               
             
          
           
               
                 Harmalan 
                 600 
                 20 
                 600 
                 10 
                 600 
                 15 
               
               
                 Tetrahydroharmane 
                 600 
                 15 
                 600 
                 15 
                 600 
                 10 
               
               
                 Harmane 
                 600 
                 45 
                 600 
                 35 
                 600 
                 35 
               
               
                 Tetrahydroharmine 
                 600 
                 0 
                 600 
                 10 
                 600 
                 0 
               
               
                 Harmine 
                 600 
                 20 
                 600 
                 15 
                 600 
                 15 
               
               
                 Harmol 
                 600 
                 50 
                 600 
                 20 
                 600 
                 45 
               
               
                 I a -1 
                 600 
                 30 
                 600 
                 20 
                 600 
                 25 
               
               
                 I a -3 
                 600 
                 50 
                 600 
                 35 
                 600 
                 50 
               
               
                 I a -4 
                 600 
                 10 
                 600 
                 10 
                 600 
                 5 
               
               
                 I a -5 
                 600 
                 10 
                 600 
                 15 
                 600 
                 10 
               
               
                 I a -6 
                 600 
                 45 
                 600 
                 20 
                 600 
                 35 
               
               
                 I a -7 
                 600 
                 35 
                 600 
                 30 
                 600 
                 25 
               
               
                 I a -8 
                 600 
                 70 
                 600 
                 15 
                 600 
                 65 
               
               
                 I a -9 
                 600 
                 5 
                 600 
                 20 
                 600 
                 5 
               
               
                 I a -10 
                 600 
                 30 
                 600 
                 40 
                 600 
                 30 
               
               
                 I a -11 
                 600 
                 10 
                 600 
                 10 
                 600 
                 10 
               
               
                 I a -14 
                 600 
                 25 
                 600 
                 30 
                 600 
                 20 
               
               
                 I a -15 
                 600 
                 15 
                 600 
                 15 
                 600 
                 5 
               
               
                 I a -16 
                 600 
                 10 
                 600 
                 5 
                 600 
                 10 
               
               
                 I b -1 
                 600 
                 25 
                 600 
                 25 
                 600 
                 25 
               
               
                 I b -2 
                 600 
                 10 
                 600 
                 25 
                 600 
                 10 
               
               
                 I b -5 
                 600 
                 50 
                 600 
                 30 
                 600 
                 35 
               
               
                 I b -6 
                 600 
                 45 
                 600 
                 20 
                 600 
                 40 
               
               
                 I b -7 
                 600 
                 5 
                 600 
                 20 
                 600 
                 5 
               
               
                 I b -8 
                 600 
                 5 
                 600 
                 20 
                 600 
                 0 
               
               
                 I b -9 
                 600 
                 15 
                 600 
                 10 
                 600 
                 10 
               
               
                 I b -10 
                 600 
                 30 
                 600 
                 15 
                 600 
                 25 
               
               
                 I b -11 
                 600 
                 5 
                 600 
                 20 
                 600 
                 5 
               
               
                 I b -12 
                 600 
                 50 
                 600 
                 30 
                 600 
                 50 
               
               
                 I b -13 
                 600 
                 60 
                 600 
                 30 
                 600 
                 55 
               
               
                 I b -14 
                 600 
                 10 
                 600 
                 30 
                 600 
                 10 
               
               
                 I b -15 
                 600 
                 20 
                 600 
                 20 
                 600 
                 30 
               
               
                 I b -16 
                 600 
                 65 
                 600 
                 50 
                 600 
                 50 
               
               
                 I b -17 
                 600 
                 45 
                 600 
                 30 
                 600 
                 40 
               
               
                 I b -18 
                 600 
                 5 
                 600 
                 5 
                 600 
                 5 
               
               
                 I b -19 
                 600 
                 5 
                 600 
                 60 
                 600 
                 10 
               
               
                 I b -20 
                 600 
                 65 
                 600 
                 30 
                 600 
                 60 
               
               
                 I c -1 
                 600 
                 75 
                 600 
                 55 
                 600 
                 60 
               
               
                 I c -2 
                 600 
                 10 
                 600 
                 30 
                 600 
                 5 
               
               
                 I c -3 
                 600 
                 25 
                 600 
                 40 
                 600 
                 30 
               
               
                 I c -4 
                 600 
                 30 
                 600 
                 35 
                 600 
                 35 
               
               
                 I c -5 
                 600 
                 25 
                 600 
                 25 
                 600 
                 20 
               
               
                 I c -6 
                 600 
                 45 
                 600 
                 35 
                 600 
                 40 
               
               
                 I c -7 
                 600 
                 5 
                 600 
                 30 
                 600 
                 5 
               
               
                 I c -8 
                 600 
                 20 
                 600 
                 35 
                 600 
                 15 
               
               
                 I c -9 
                 600 
                 35 
                 600 
                 30 
                 600 
                 40 
               
               
                 I c -10 
                 600 
                 25 
                 600 
                 30 
                 600 
                 30 
               
               
                 I c -11 
                 600 
                 65 
                 600 
                 40 
                 600 
                 55 
               
               
                 I c -12 
                 600 
                 15 
                 600 
                 30 
                 600 
                 15 
               
               
                 I c -13 
                 600 
                 30 
                 600 
                 15 
                 600 
                 35 
               
               
                 I c -14 
                 600 
                 40 
                 600 
                 35 
                 600 
                 45 
               
               
                 I c -15 
                 600 
                 15 
                 600 
                 15 
                 600 
                 20 
               
               
                 I c -16 
                 600 
                 20 
                 600 
                 10 
                 600 
                 30 
               
               
                 I c -17 
                 600 
                 25 
                 600 
                 20 
                 600 
                 20 
               
               
                 I c -18 
                 600 
                 10 
                 600 
                 20 
                 600 
                 15 
               
               
                 I c -19 
                 600 
                 70 
                 600 
                 50 
                 600 
                 60 
               
               
                 I c -20 
                 600 
                 35 
                 600 
                 20 
                 600 
                 30 
               
               
                 I c -21 
                 600 
                 40 
                 600 
                 45 
                 600 
                 35 
               
               
                 I c -22 
                 600 
                 40 
                 600 
                 20 
                 600 
                 50 
               
               
                 I c -23 
                 600 
                 15 
                 600 
                 10 
                 600 
                 10 
               
               
                 I c -24 
                 600 
                 45 
                 600 
                 20 
                 600 
                 50 
               
               
                 I c -25 
                 600 
                 45 
                 600 
                 20 
                 600 
                 55 
               
               
                 I c -26 
                 600 
                 25 
                 600 
                 20 
                 600 
                 30 
               
               
                 I c -27 
                 600 
                 20 
                 600 
                 30 
                 600 
                 30 
               
               
                 I c -28 
                 600 
                 45 
                 600 
                 45 
                 600 
                 40 
               
               
                 I c -29 
                 600 
                 20 
                 600 
                 25 
                 600 
                 15 
               
               
                 I d -1 
                 600 
                 35 
                 600 
                 15 
                 600 
                 35 
               
               
                 I d -2 
                 600 
                 40 
                 600 
                 40 
                 600 
                 40 
               
               
                 I d -3 
                 600 
                 25 
                 600 
                 40 
                 600 
                 25 
               
               
                 I d -4 
                 600 
                 10 
                 600 
                 30 
                 600 
                 15 
               
               
                 I d -5 
                 600 
                 5 
                 600 
                 30 
                 600 
                 25 
               
               
                 I d -6 
                 600 
                 35 
                 600 
                 25 
                 600 
                 50 
               
               
                 I d -7 
                 600 
                 40 
                 600 
                 30 
                 600 
                 40 
               
               
                   
               
             
          
         
       
     
         [0307]    Table 3 indicates most of β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloids and their derivatives (I a , I b , I c  and I d ) show certain activity against armyworms, cotton bollworms and corn borers. Particularly, compounds I a -8, I b -13, I b -16, I b -20, I c -1, I c -11 and I c -19 show broad-spectrum activity. 
       Embodiment 24 
     Determination of Activity Against Mosquito Larvae, and the Determination Procedure is as Follows 
       [0308]    Test of Activity Against Mosquito Larvae 
         [0309]    Experimental method of mosquito larvae:  culex pipiens pallens , a normal colony raised indoors. Weigh about 5 mg of the compound for test, put it in a penicillin vial, add 5 mL of acetone (or an appropriate solvent), and shake and dissolve it to obtain a 1000 ppm mother solution. Pipette 0.5 mL of the mother solution, add it to a 100 mL beaker filled with 89.9 mL of water, select 10 mosquito larvae at the beginning of the fourth instar, and pour them to a beaker together with 10 mL of feeding solution. The concentration of the drug solution is 5 ppm. Put it in a standard treatment room and check the result 24 h later. Use an aqueous solution containing 0.5 mL of test solvent as a blank. 
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                 Test results of the activity of some of β-carboline, dihydro-β-carboline and 
               
               
                 tetrahydro-β-carboline alkaloids and their derivatives (I a , I b , I c  and I d ) 
               
               
                 against mosquito larvae: 
               
             
          
           
               
                   
                 Mosquito larvae 
                   
                 Larvae 
               
             
          
           
               
                   
                 Concen- 
                   
                   
                 Concen- 
                   
               
               
                   
                 tration 
                 Mortality 
                   
                 tration 
                 Mortality 
               
               
                 No. 
                 (mg/kg) 
                 (%) 
                 No. 
                 (mg/kg) 
                 (%) 
               
               
                   
               
             
          
           
               
                 Harmalan 
                 10 
                 35 
                 I b -19 
                 10 
                 20 
               
               
                 Tetrahydroharmane 
                 10 
                 30 
                 I b -20 
                 10 
                 100 
               
               
                 Harmane 
                 10 
                 100 
                   
                 5 
                 40 
               
               
                   
                 5 
                 10 
                 I c -1 
                 10 
                 100 
               
               
                 Tetrahydroharmine 
                 10 
                 15 
                   
                 5 
                 80 
               
               
                 Harmine 
                 10 
                 45 
                 I c -2 
                 10 
                 20 
               
               
                 Harmol 
                 10 
                 100 
                 I c -3 
                 10 
                 55 
               
               
                   
                 5 
                 30 
                 I c -4 
                 10 
                 65 
               
               
                 I a -1 
                 10 
                 50 
                 I c -5 
                 10 
                 50 
               
               
                 I a -3 
                 10 
                 100 
                 I c -6 
                 10 
                 100 
               
               
                   
                 5 
                 60 
                   
                 5 
                 20 
               
               
                 I a -4 
                 10 
                 30 
                 I c -7 
                 10 
                 10 
               
               
                 I a -5 
                 10 
                 30 
                 I c -8 
                 10 
                 35 
               
               
                 I a -6 
                 10 
                 100 
                 I c -9 
                 10 
                 75 
               
               
                   
                 5 
                 20 
                 I c -10 
                 10 
                 50 
               
               
                 I a -7 
                 10 
                 65 
                 I c -11 
                 10 
                 100 
               
               
                 I a -8 
                 10 
                 100 
                   
                 5 
                 40 
               
               
                   
                 5 
                 60 
                 I c -12 
                 10 
                 15 
               
               
                 I a -9 
                 10 
                 25 
                 I c -13 
                 10 
                 60 
               
               
                 I a -10 
                 10 
                 65 
                 I c -14 
                 10 
                 75 
               
               
                 I a -11 
                 10 
                 50 
                 I c -15 
                 10 
                 30 
               
               
                 I a -14 
                 10 
                 35 
                 I c -16 
                 10 
                 40 
               
               
                 I a -15 
                 10 
                 35 
                 I c -17 
                 10 
                 50 
               
               
                 I a -16 
                 10 
                 20 
                 I c -18 
                 10 
                 25 
               
               
                 I b -1 
                 10 
                 55 
                 I c -19 
                 10 
                 100 
               
               
                 I b -2 
                 10 
                 30 
                   
                 5 
                 80 
               
               
                 I b -5 
                 10 
                 100 
                 I c -20 
                 10 
                 75 
               
               
                   
                 5 
                 30 
                 I c -21 
                 10 
                 85 
               
               
                 I b -6 
                 10 
                 100 
                 I c -22 
                 10 
                 85 
               
               
                   
                 5 
                 20 
                 I c -23 
                 10 
                 35 
               
               
                 I b -7 
                 10 
                 15 
                 I c -24 
                 10 
                 100 
               
               
                 I b -8 
                 10 
                 10 
                   
                 5 
                 10 
               
               
                 I b -9 
                 10 
                 35 
                 I c -25 
                 10 
                 100 
               
               
                 I b -10 
                 10 
                 60 
                   
                 5 
                 10 
               
               
                 I b -11 
                 10 
                 15 
                 I c -26 
                 10 
                 55 
               
               
                 I b -12 
                 10 
                 100 
                 I c -27 
                 10 
                 40 
               
               
                   
                 5 
                 40 
                 I c -28 
                 10 
                 100 
               
               
                 I b -13 
                 10 
                 100 
                   
                 5 
                 20 
               
               
                   
                 5 
                 60 
                 I c -29 
                 10 
                 45 
               
               
                 I b -14 
                 10 
                 30 
                 I d -1 
                 10 
                 75 
               
               
                 I b -15 
                 10 
                 40 
                 I d -2 
                 10 
                 80 
               
               
                 I b -16 
                 10 
                 100 
                 I d -3 
                 10 
                 50 
               
               
                   
                 5 
                 60 
                 I d -4 
                 10 
                 25 
               
               
                 I b -17 
                 10 
                 100 
                 I d -5 
                 10 
                 10 
               
               
                   
                 5 
                 10 
                 I d -6 
                 10 
                 65 
               
               
                 I b -18 
                 10 
                 10 
                 I d -7 
                 10 
                 80 
               
               
                   
               
             
          
         
       
     
         [0310]    Table 4 indicates most of β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloids and their derivatives (I a , I b , I c  and I d ) show high activity against  culex pipiens  larvae, and I a -3, I a -8, I b -13, I b -16, I c -1 and I c -19 still show high activity at 5 mg/kg.