Application of cryptolepine and derivatives thereof in prevention and control of nematodes

Abstract

The invention relates to the technical field of animal and plant parasite prevention and control, in particular to application of cryptolepine and derivatives thereof to prevention and control of nematodes, including prevention and control of plant nematodes and / or animal nematodes. Insecticidal tests prove that cryptolepine and derivatives thereof have remarkable killing activity on plant nematodes and animal nematodes, and are expected to be widely applied in the aspects of agriculture and animal husbandry.

Description

Technical Field

[0001] The invention relates to the technical field of animal and plant parasite control, and in particular to the application of cephalosporin and its derivatives in controlling nematodes. Background Art

[0002] The genus of Glechoma is a genus under the family Apocynaceae, with a total of 12 species, mainly distributed in tropical regions of Asia and Africa. The plant resources of this genus are rich, with a wide coverage, and can be cultivated, with broad prospects for development and utilization. There are two main types of Glechoma plants in my country: Glechoma and Uncaria, which are mainly distributed in southern and southwestern my country.

[0003] At present, the research on the genus Leucanthus mainly focuses on the traditional African medicinal material Leucanthus sanguinea ( Cryptolepis sanguineous ) on. Sanguinea sanguinea is a very important traditional Chinese medicine in West Africa. The root of this plant has been used to treat jaundice and hepatitis, and the root juice can be used to treat gastrointestinal disorders. It is also considered a very effective antimalarial drug for controlling and treating malaria infection. In addition, the root of Sanguinea sanguinea is also used in traditional medicine to treat various colds, urinary tract infections, upper respiratory tract infections and sepsis, and can effectively control a variety of related diseases including amoebic dysentery and diabetes.

[0004] In 1951, Gellert first isolated the alkaloid cryptolepine with an indole and quinoline structure from the sanguine vine. In 1996, Wright et al. found that cryptolepine had the same activity as chloroquine against Plasmodium falciparum in vitro. At the same time, in vivo studies found that cryptolepine had moderate inhibitory activity when given orally to mice infected with Plasmodium falciparum, and could inhibit 80% of Plasmodium falciparum under the condition of 50 mg / kg / day administration. In 2011, Lavrado et al. reported the synthesis of the C-11 basic side chain derivatives of cryptolepine and the evaluation of its anti-malarial and cytotoxicity. In 2019, JM Yuan et al. evaluated the antiproliferative effects of 30 cryptolepine derivatives on four human tumor cell lines (HepG-2, T24, MGC-803, NCI-H460) and a human normal liver cell line (HL-7702). In 2013, Olajide et al. also reported the anti-inflammatory activity mechanism of leucoderma alkaloids on lipopolysaccharide-induced neuroinflammation in rat microglia. In 2021, Liu Yingqian et al. designed and synthesized a series of leucoderma alkaloids and their derivatives, and evaluated their antibacterial activity against four important agricultural fungi (tomato blastic wilt, tomato gray mold, Fusarium graminearum, and Sclerotinia sclerotiorum).

[0005] However, to date, there has been no research on the use of cephalosporin and its derivatives in controlling nematodes. Summary of the invention

[0006] The present invention aims to solve at least one of the technical problems existing in the related art. To this end, the present invention aims to provide the use of cephalaenopsis linalool and its derivatives in controlling nematodes.

[0007] In order to achieve the above object, the technical solution adopted by the present invention is: The application of leucoderma alkaloids and its derivatives in controlling nematodes includes the control of plant nematodes and / or animal nematodes.

[0008] Furthermore, the plants include crops and / or flowers.

[0009] Furthermore, the crops include one or more of tomatoes, eggplants, bitter gourds, cucumbers, melons, loofahs, celery, peppers, cowpeas, kidney beans, potatoes, tobacco, beets, Chinese cabbage, cauliflower, kale, radishes, carrots, onions, garlic, rapeseed, citrus, grapes, bananas, pineapples, passion fruit, strawberries, pitaya and kiwifruit.

[0010] Furthermore, the flowers include one or more of lily, rose, carnation, cactus, daffodil, hyacinth, ginger flower, gerbera, water lily, lotus and cattail.

[0011] Furthermore, the plant nematodes include one or more of root-knot nematodes, stem nematodes, leaf nematodes, cyst nematodes, root rot nematodes, reniform nematodes, semi-penetrating nematodes and pine wood nematodes.

[0012] Furthermore, the animal nematode includes Caenorhabditis elegans.

[0013] Further, the structural formula of cephalaenopsis alkaloids is shown below: .

[0014] Furthermore, the derivative of cephalaenopsis alkaloids is selected from any one or more of the following structural formulas: , , , , , , , , , , , , , , , , , , , , , , , , , , , , .

[0015] Furthermore, the application includes preparing pesticides using cephalaline and / or its derivatives as active ingredients.

[0016] Furthermore, the application includes preparing veterinary drugs using cephalaline and / or its derivatives as active ingredients.

[0017] The above one or more technical solutions in the embodiments of the present invention have at least one of the following technical effects: The present invention provides the use of cephalosporin and its derivatives in preventing and controlling nematodes. Insecticidal tests have shown that cephalosporin and its derivatives have significant killing activity against plant nematodes and animal nematodes, and are expected to be widely used in agriculture and animal husbandry.

[0018] Additional aspects and advantages of the present invention will be given in part in the following description and in part will be obvious from the following description, or will be learned through practice of the present invention. DETAILED DESCRIPTION

[0019] In order to make the purpose, technical scheme and advantages of the present invention clearer, the technical scheme of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in the field without creative work are within the scope of protection of the present invention. The following embodiments are used to illustrate the present invention, but cannot be used to limit the scope of the present invention.

[0020] In the following examples, the experimental methods used are conventional methods unless otherwise specified, and the materials, reagents, etc. used are all available from commercial sources unless otherwise specified.

[0021] Example 1 Preparation of cephalosporin and its derivatives.

[0022] Bilobaine , prepared according to the method disclosed in patent (CN 114762503 A), and the derivatives of leucoderma alkaloids were prepared according to the method disclosed in the following documents: Document 1: Lavrado J, Cabal GG, Prudêncio M, Mota MM, Gut J, RosenthalPJ, Díaz C, Guedes RC, dos Santos DJ, Bichenkova E, Douglas KT, Moreira R,Paulo A. Incorporation of basic side chains into cryptolepine scaffold: structure-antimalarial activity relationships and mechanistic studies. J MedChem. 2011 Feb 10;54(3):734-750. Document 2: Bowler JT, Clausen CR, Blackburn DJ, Wu W. Convenientsynthesis of N1-substituted orotic acid derivatives. Tetrahedron Lett. 2014Nov 19;55(47):6465-6466. Bilobaine derivatives : Yellow solid, melting point: >250 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 11.64 (s, 1H), 8.69 (d, J = 8.5 Hz, 2H), 8.51(d, J = 8.4 Hz, 1H), 8.30 (d, J = 8.9 Hz, 1H), 8.04 – 7.96 (m, 1H), 7.84 (d, J =8.4 Hz, 1H), 7.75 – 7.65 (m, 2H), 7.41 – 7.31 (m, 1H), 4.55 (s, 3H), 4.04 (t, J = 6.4 Hz, 2H), 1.94 – 1.79 (m, 2H), 1.04 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, DMSO- d 6 ) d 144.0, 142.9, 137.5, 135.8, 132.7, 130.9,124.7, 124.4, 124.4, 121.2, 117.8, 116.6, 115.5, 114.8, 113.9, 47.4, 38.5,23.5, 11.7; HRMS (ESI), calculated value C 19 H 20 N 3 + [M] + 290.1652, experimental measurement value 290.1651.

[0023] Bilobaine derivatives : Yellow solid, melting point: 230-231 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 11.61 (s, 1H), 8.69 (d, J = 7.7 Hz, 2H), 8.50(d, J = 7.9 Hz, 1H), 8.29 (d, J = 8.5 Hz, 1H), 8.06 – 7.95 (m, 1H), 7.84 (d, J =7.8 Hz, 1H), 7.76 – 7.61 (m, 2H), 7.42 – 7.28 (m, 1H), 4.54 (s, 3H), 4.06 (s,2H), 1.93 – 1.69 (m, 2H), 1.53 – 1.30 (m, 4H), 0.90 (t, J = 6.4 Hz, 3H); 13 C NMR (100 MHz, DMSO- d 6 ) d143.5, 142.4, 137.0, 135.3, 132.2, 130.4,124.2, 123.9, 120.7, 117.3, 116.1, 115.0, 114.3, 113.4, 45.4, 38.0, 29.3,28.4, 21.9, 13.9; HRMS (ESI), calculated value C 21 H 24 N 3 + [M] + 318.1965, experimental measurement value 318.1964.

[0024] Three derivatives of leucophylla : Yellow solid, melting point: 171-172 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 11.62 (s, 1H), 8.69 (d, J = 7.8 Hz, 2H), 8.51(d, J = 8.1 Hz, 1H), 8.31 (d, J = 8.5 Hz, 1H), 8.05 – 7.96 (m, 1H), 7.84 (d, J =7.9 Hz, 1H), 7.75 – 7.64 (m, 2H), 7.41 – 7.30 (m, 1H), 4.55 (s, 3H), 4.07 (s,2H), 1.44 (s, 2H), 1.24 (d, J = 52.3 Hz, 18H), 0.82 (t, J = 6.3 Hz, 3H); 13 C NMR (100 MHz, DMSO- d 6 ) d 144.0, 143.0, 137.6, 135.8, 132.7, 130.9,124.7, 124.4, 121.2, 117.8, 116.6, 115.6, 114.9, 113.9, 45.9, 38.5, 31.7,30.1, 29.5, 29.4, 29.2, 26.7, 22.5, 14.4; HRMS (ESI), calculated value C 28 H 38 N 3 + [M] + 416.3060, experimental measurement value 416.3060.

[0025] Four derivatives of leucophylla : Yellow solid, melting point: 238-239 °C; 1 H NMR (400 MHz, MeOH- d 4 ) d 8.57 (d, J = 8.6 Hz, 1H), 8.49 (d, J = 8.5Hz, 1H), 8.24 (d, J = 8.9 Hz, 1H), 8.04 – 7.97 (m, 1H), 7.83 (d, J = 8.4 Hz,1H), 7.75 – 7.66 (m, 2H), 7.45 – 7.37 (m, 1H), 4.61 (s, 3H), 4.17 (t, J = 7.1Hz, 2H), 1.89 – 1.78 (m, 3H), 1.03 (d, J = 6.3 Hz, 6H); 13 C NMR (100 MHz, MeOH- d 4 ) d 144.1, 143.1, 137.7, 136.1, 132.3, 130.7,124.2, 123.7, 123.3, 121.0, 116.7, 115.6, 114.8, 113.1, 110.0, 44.1, 38.7,37.3, 25.6, 21.5; HRMS (ESI), calculated value C 21 H 24 N 3 + [M] + 318.1965, experimental measurement value 318.1966.

[0026] Bilobaine derivatives : Yellow solid, melting point: 200-201 °C; 1H NMR (400 MHz, DMSO- d 6 ) d 11.75 (s, 1H), 8.75 (d, J = 8.1 Hz, 1H), 8.59 (d, J = 8.5 Hz, 2H), 8.38 (d, J = 8.8 Hz, 1H), 8.09 – 7.99 (m, 1H), 7.85(d, J = 8.4 Hz, 1H), 7.81 – 7.68 (m, 2H), 7.46 – 7.35 (m, 1H), 4.63 (s, 3H), 4.02 (s, 2H), 1.94 – 1.85 (m, 1H), 1.52 – 1.33 (m, 4H), 1.32 – 1.19 (m, 4H),0.87 (t, J = 7.4 Hz, 3H), 0.82 (t, J = 7.1 Hz, 3H); 13 C NMR (100 MHz, DMSO- d 6 ) d 144.4, 143.1, 137.7, 136.3, 132.8, 131.2,125.0, 124.6, 124.3, 121.4, 118.0, 117.3, 115.9, 115.3, 114.0, 49.6, 38.6,30.5, 28.5, 23.9, 22.9, 14.3, 10.9; HRMS (ESI), calculated value C 24 H 30 N 3 + [M] + 360.2434, experimental measurement value 360.2433.

[0027] 6. Derivatives of leucophylla : Yellow solid, melting point: >250 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 11.70 (s, 1H), 8.87 (s, 1H), 8.73 (d, J = 8.5Hz, 1H), 8.52 (d, J= 8.4 Hz, 1H), 8.32 (d, J = 8.9 Hz, 1H), 8.05 – 7.97 (m, 1H), 7.85 (d, J = 8.3 Hz, 1H), 7.74 – 7.66 (m, 2H), 7.40 – 7.32 (m, 1H), 4.57 (s,3H), 3.97 (d, J = 6.7 Hz, 2H), 1.38 – 1.26 (m, 1H), 0.63 – 0.54 (m, 2H), 0.52 –0.42 (m, 2H); 13 C NMR (100 MHz, DMSO- d 6 ) d 143.9, 143.0, 137.6, 135.8, 132.8, 131.0,124.7, 124.5, 124.4, 121.2, 117.8, 116.7, 115.6, 114.9, 114.0, 50.2, 38.5,12.0, 4.3; HRMS (ESI), calculated value C 20 H 20 N 3 + [M] + 302.1652, experimental measurement value 302.1650.

[0028] Bilobaine derivatives : Yellow solid, melting point: 248-249 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 11.63 (s, 1H), 8.76 (d, J = 8.4 Hz, 1H), 8.55(d, J = 8.3 Hz, 1H), 8.46 – 8.29 (m, 2H), 8.06 – 7.97 (m, 1H), 7.88 (d, J= 8.3Hz, 1H), 7.78 – 7.66 (m, 2H), 7.44 – 7.33 (m, 1H), 5.02 (s, 1H), 4.60 (s,3H), 2.29 – 2.14 (m, 2H), 1.98 – 1.89 (m, 2H), 1.88 – 1.78 (m, 2H), 1.73 (d, J = 6.1 Hz, 2H); 13 C NMR (100 MHz, DMSO- d 6 ) d 143.5, 143.0, 137.6, 136.0, 132.8, 131.1,124.9, 124.8, 124.3, 121.2, 117.8, 116.8, 115.7, 114.9, 114.0, 57.0, 38.6,34.2, 24.5; HRMS (ESI), calculated value C 21 H 22 N 3 + [M] + 316.1808, experimental measurement value 316.1808.

[0029] Bilobaine derivatives : Yellow solid, melting point: 243-244 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 11.86 (s, 1H), 8.77 (d, J = 8.5 Hz, 2H), 8.56(d, J = 8.4 Hz, 1H), 8.35 (d, J = 8.9 Hz, 1H), 8.02 (t, J = 7.8 Hz, 1H), 7.88 (d, J =8.4 Hz, 1H), 7.79 – 7.67 (m, 2H), 7.39 (t, J = 7.6 Hz, 1H), 4.61 (s, 3H), 3.98(s, 2H), 1.85 (d, J= 10.3 Hz, 3H), 1.64 (d, J = 23.4 Hz, 3H), 1.23 – 1.11 (m, 3H), 1.10 – 0.99 (m, 2H); 13 C NMR (100 MHz, DMSO- d 6 ) d 144.3, 143.0, 137.7, 136.0, 132.8, 131.0,124.8, 124.5, 124.5, 121.3, 118.0, 117.1, 115.8, 115.1, 114.1, 54.8, 52.0,38.5, 30.7, 26.4, 25.8; HRMS (ESI), calculated value C 23 H 26 N 3 + [M] + 344.2121, experimental measurement value 344.2122.

[0030] Bilobaine derivatives : Yellow solid, melting point: 234-235 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 11.87 (s, 1H), 8.88 (s, 1H), 8.73 (d, J = 7.5Hz, 1H), 8.53 (d, J = 7.4 Hz, 1H), 8.32 (d, J = 8.1 Hz, 1H), 8.05 – 7.97 (m, 1H),7.87 (d, J = 7.3 Hz, 1H), 7.76 – 7.65 (m, 2H), 7.37 (t, J = 6.2 Hz, 1H), 4.58 (s,3H), 4.09 (s, 2H), 1.82 (s, 2H), 1.73 – 1.50 (m, 6H), 1.35 (d, J = 5.1 Hz, 2H),1.21 – 1.10 (m, 3H), 0.91 – 0.80 (m, 2H); 13 C NMR (100 MHz, DMSO- d 6 ) d 144.1, 143.0, 137.7, 135.7, 132.7, 130.9,124.7, 124.6, 124.3, 121.2, 117.8, 116.8, 115.6, 115.0, 114.0, 46.2, 38.5,37.2, 34.4, 33.2, 27.6, 26.6, 26.2; HRMS (ESI), calculated value C 25 H 30 N 3 + [M] + 372.2434, experimental measurement value 372.2437.

[0031] Bilobaine derivatives : Yellow solid, melting point: 235-236 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 8.60 (d, J = 8.4 Hz, 1H), 8.42 (d, J = 8.4 Hz,1H), 8.23 ​​(d, J = 8.9 Hz, 1H), 7.95 – 7.89 (m, 1H), 7.72 (d, J = 8.4 Hz, 1H),7.63 – 7.55 (m, 2H), 7.23 – 7.18 (m, 1H), 4.51 (s, 3H), 4.28 – 4.21 (m, 2H),3.20 (s, 2H); 13 C NMR (100 MHz, DMSO- d 6 ) d 145.6, 145.0, 137.1, 135.2, 131.8, 129.5,124.2, 124.1, 123.4, 120.8, 119.7, 117.3, 115.4, 115.4, 46.6, 40.8, 38.0; HRMS (ESI), calculated value C 18 H 19 N 4 + [M] + 291.1604, experimental measurement value 291.1602.

[0032] 11. : Yellow solid, melting point: 198-199 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 8.62 (d, J = 8.2 Hz, 1H), 8.41 (d, J = 8.2 Hz,1H), 8.25 (d, J = 8.8 Hz, 1H), 7.91 (t, J = 7.4 Hz, 1H), 7.67 (d, J = 8.3 Hz, 1H),7.59 (t, J = 7.1 Hz, 1H), 7.50 (t, J = 7.0 Hz, 1H), 7.14 – 7.09 (m, 1H), 4.57 (s,3H), 4.52 (s, 2H), 3.12 (s, 1H), 2.93 (s, 2H), 2.09 (s, 2H), 1.61 (s, 2H); 13 C NMR (100 MHz, DMSO- d 6 ) d 149.5, 148.8, 145.2, 136.6, 135.4, 131.2,128.2, 124.3, 124.0, 122.7, 118.1, 117.1, 116.9, 115.3, 114.5, 42.1, 38.6,37.9, 30.2; HRMS (ESI), calculated value C 19 H 21 N 4 + [M] + 305.1761, experimental measurement value 305.1759.

[0033] Bilobaine derivatives : Yellow solid, melting point: 203-204 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 8.69 (d, J = 8.5 Hz, 1H), 8.51 (d, J = 8.4 Hz,1H), 8.31 (d, J = 8.9 Hz, 1H), 8.01 – 7.95 (m, 1H), 7.81 (d, J = 8.5 Hz, 1H),7.71 – 7.61 (m, 2H), 7.28 (t, J = 7.6 Hz, 1H), 4.59 (s, 3H), 4.23 (t, J = 6.7 Hz,2H), 2.90 (t, J = 7.1 Hz, 2H), 1.94 – 1.83 (m, 2H), 1.78 – 1.66 (m, 2H); 13 C NMR (100 MHz, DMSO- d 6 ) d 145.6, 144.2, 137.3, 135.7, 132.2, 129.9,124.5, 124.3, 123.7, 120.0, 119.6, 117.6, 115.3, 115.2, 115.0, 44.7, 39.1,38.3, 27.4, 24.9; HRMS (ESI), calculated value C 20 H 23 N 4 + [M] + 319.1917, experimental measurement value 319.1918.

[0034] 13 : Yellow solid, melting point: 221-222 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d8.64 (d, J = 8.3 Hz, 1H), 8.41 (d, J = 8.5 Hz,1H), 8.21 (d, J = 8.9 Hz, 1H), 7.91 (t, 1H), 7.71 (d, J = 8.4 Hz, 1H), 7.63 –7.53 (m, 2H), 7.19 (t, 1H), 4.51 (s, 3H), 3.50 (t, J = 10.6, 6.6 Hz, 1H), 1.85(s, 2H), 1.33 (d, J = 6.5 Hz, 3H); 13 C NMR (100 MHz, DMSO- d 6 ) d 170.2, 145.2, 144.8, 136.8, 134.5, 131.3,128.8, 123.8, 123.7, 122.8, 120.7, 119.1, 116.7, 115.3, 115.0, 46.7, 37.5,22.6, 17.2; HRMS (ESI), calculated value C 19 H 21 N 4 + [M] + 305.1761, experimental measurement value 305.1760.

[0035] 14-Chenamine derivatives : Yellow solid, melting point: 252-253 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 8.73 (d, J = 8.4 Hz, 1H), 8.40 (d, J = 8.4 Hz,1H), 8.15 (d, J = 8.8 Hz, 1H), 7.91 – 7.85 (m, 1H), 7.69 (d, J= 8.4 Hz, 1H),7.59 – 7.50 (m, 2H), 7.21 – 7.15 (m, 1H), 4.49 (s, 3H), 4.14 (s, 2H), 1.88(s, 1H), 1.41 (s, 6H), 1.12 (s, 2H); 13 C NMR (100 MHz, DMSO- d 6 ) d 146.2, 137.6, 131.4, 128.5, 124.8, 123.9,122.7, 122.6, 119.2, 116.9, 116.8, 115.8, 52.7, 37.7, 26.7, 24.9; HRMS (ESI), calculated value C 20 H 23 N 4 + [M] + 319.1917, experimental measurement value 319.1917.

[0036] 15. Bilobaine derivatives : Yellow solid, melting point: 233-234 °C; 1 H NMR (400 MHz, MeOH- d 4 ) d 8.50 (d, J = 8.5 Hz, 1H), 8.41 (d, J = 8.5 Hz,1H), 8.19 (d, J = 8.9 Hz, 1H), 7.99 – 7.94 (m, 1H), 7.76 (d, J = 8.4 Hz, 1H),7.68 – 7.62 (m, 2H), 7.37 – 7.31 (m, 1H), 4.54 (s, 3H), 4.24 – 4.17 (m, 2H),3.23 – 3.19 (m, 2H), 2.83 (q, J = 7.2 Hz, 2H), 1.16 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, MeOH- d4 ) d 143.4, 137.4, 136.1, 132.1, 130.5, 124.9,124.1, 123.6, 123.1, 120.7, 116.7, 115.5, 115.2, 113.3, 45.2, 43.7, 37.2,13.2; HRMS (ESI), calculated value C 20 H 23 N 4 + [M] + 319.1917, experimental measurement value 319.1917.

[0037] Bilobaine derivatives : Yellow solid, melting point: 247-248 °C; 1 H NMR (400 MHz, MeOH- d 4 ) d 8.50 (d, J = 8.5 Hz, 2H), 8.26 (d, J = 8.9Hz, 1H), 8.04 – 7.98 (m, 1H), 7.77 – 7.68 (m, 3H), 7.43 – 7.37 (m, 1H), 4.64(s, 3H), 4.19 (t, 2H), 2.98 (t, 2H), 2.50 (s, 6H). 13 C NMR (100 MHz, MeOH- d 4 ) d 143.5, 137.5, 132.2, 130.7, 124.2, 123.7, 122.9, 120.8, 116.8, 115.5, 115.2,113.2, 58.9, 44.3, 43.6, 37.2; HRMS (ESI), calculated value C 20 H 23 N 4 + [M] + 319.1917, experimental measurement value 319.1919.

[0038] 17 : Yellow solid, melting point: 229-230 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 8.97 (s, 1H), 8.64 – 8.55 (m, 2H), 8.36 (d, J = 8.9 Hz, 1H), 8.06 – 7.99 (m, 1H), 7.79 – 7.70 (m, 3H), 7.43 – 7.35 (m, 1H), 4.62 (s, 3H), 4.13 (s, 2H), 3.01 (s, 2H), 2.75 (d, J = 6.9 Hz, 4H), 0.98 (t, J =7.0 Hz, 6H); 13 C NMR (100 MHz, DMSO- d 6 ) d 144.4, 143.4, 137.5, 135.9, 132.7, 131.0,124.9, 124.5, 123.9, 121.0, 118.0, 118.0, 115.7, 115.5, 114.0, 53.4, 47.7,44.7, 38.4, 11.2; HRMS (ESI), calculated value C 22 H 27 N 4 + [M] + 347.2230, experimental measurement value 347.2231.

[0039] 18-Citrine derivatives : Yellow solid, melting point: 187-188 °C; 1 H NMR (400 MHz, MeOH- d 4 ) d 8.48 (d, J = 8.4 Hz, 1H), 8.38 (d, J = 8.5 Hz,1H), 8.16 (d, J = 8.9 Hz, 1H), 8.00 – 7.92 (m, 1H), 7.75 (d, J= 8.4 Hz, 1H),7.70 – 7.60 (m, 2H), 7.32 (t, J = 7.7 Hz, 1H), 4.49 (s, 3H), 4.20 (t, J = 6.3 Hz,2H), 2.87 (t, J = 6.0 Hz, 2H), 2.47 (s, 3H), 2.20 – 2.09 (m, 2H); 13 C NMR (100 MHz, MeOH- d 4 ) d 144.5, 144.0, 137.3, 136.1, 132.0, 130.3,124.0, 123.5, 123.0, 120.5, 116.6, 115.3, 114.9, 113.4, 100.0, 46.8, 42.9,37.1, 34.0, 28.7; HRMS (ESI), calculated value C 20 H 23 N 4 + [M] + 319.1917, experimental measurement value 319.1917.

[0040] 19 : Yellow solid, melting point: 230-231 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 9.08 (s, 1H), 8.65 – 8.53 (m, 2H), 8.35 (d,J = 8.9 Hz, 1H), 8.06 – 7.97 (m, 1H), 7.80 (d, J = 8.3 Hz, 1H), 7.76 – 7.65(m, 2H), 7.43 – 7.31 (m, 1H), 4.60 (s, 3H), 4.16 (t, J = 5.5 Hz, 2H), 2.61 (t, J = 5.7 Hz, 2H), 2.36 (s, 6H), 2.11 – 2.00 (m, 2H); 13 C NMR (100 MHz, DMSO-d 6 ) d 145.0, 143.9, 137.5, 136.3, 132.6, 130.8,124.8, 124.4, 123.9, 120.9, 118.0, 117.9, 115.6, 115.5, 114.4, 54.7, 44.2,43.5, 38.4, 26.6; HRMS (ESI), calculated value C 21 H 25 N 4 + [M] + 333.2074, experimental measurement value 333.2073.

[0041] 20 phyllotoxin derivatives : Yellow solid, melting point: 242-243 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 10.76 (s, 1H), 8.57 (d, J = 8.4 Hz, 1H), 8.36(d, J = 8.9 Hz, 1H), 8.19 (d, J = 8.4 Hz, 1H), 8.07 – 8.00 (m, 1H), 7.86 – 7.71(m, 3H), 7.42 – 7.34 (m, 1H), 4.60 (s, 3H), 4.15 (s, 2H), 3.36 (s, 1H), 2.62(s, 2H), 2.46 (s, 6H), 1.15 (s, 6H); 13 C NMR (100 MHz, DMSO- d 6 ) d 144.5, 143.0, 137.7, 135.8, 132.8, 130.9,125.0, 124.8, 123.0, 121.2, 118.1, 116.7, 115.6, 115.0, 114.0, 100.0, 69.9,57.3, 48.2, 38.4, 35.4, 25.5; HRMS (ESI), calculated value C23 H 29 N 4 + [M] + 361.2387, experimental measurement value 361.2385.

[0042] 21 : Yellow solid, melting point: 185-186 °C; 1 H NMR (400 MHz, CDCl 3 ) d 9.65 (s, 1H), 8.88 (d, J = 8.4 Hz, 1H), 8.23 ​​(d, J = 8.4 Hz, 1H), 7.97 – 7.89 (m, 2H), 7.86 – 7.80 (m, 1H), 7.56 – 7.49 (m,2H), 7.24 (d, J = 7.6 Hz, 1H), 4.54 (s, 3H), 4.45 (t, J = 5.8 Hz, 2H), 2.82 –2.73 (m, 6H), 2.29 (d, J = 5.0 Hz, 2H), 1.07 (t, J = 7.1 Hz, 6H); 13 C NMR (100 MHz, CDCl 3 ) d 144.9, 143.1, 137.4, 132.4, 130.3, 125.5,124.1, 123.1, 121.0, 116.7, 116.0, 115.6, 115.0, 114.1, 49.3, 47.0, 45.5,38.2, 26.0, 10.3; HRMS (ESI), calculated value C 23 H 29 N 4 + [M] + 361.2387, experimental measurement value 361.2387.

[0043] 22 : Yellow solid, melting point: 208-209 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 8.89 (s, 1H), 8.65 (d, J = 8.3 Hz, 1H), 8.53(d, J = 8.2 Hz, 1H), 8.33 (d, J = 8.8 Hz, 1H), 8.06 – 7.98 (m, 1H), 7.88 (d, J =8.2 Hz, 1H), 7.77 – 7.67 (m, 2H), 7.42 – 7.33 (m, 1H), 4.56 (s, 3H), 4.18 (s,2H), 3.14 – 2.78 (m, 6H), 2.17 (s, 2H), 1.67 (s, 4H), 1.52 (s, 2H); 13 C NMR (100 MHz, DMSO- d 6 ) d 143.4, 142.7, 137.0, 135.5, 132.3, 130.6,124.3, 124.0, 123.9, 120.8, 117.4, 116.2, 115.1, 114.4, 113.5, 54.2, 52.7,43.1, 38.1, 24.7, 23.3, 21.9; HRMS (ESI), calculated value C 24 H 29 N 4 + [M] + 373.2387, experimental measurement value 373.2383.

[0044] 23 : Yellow solid, melting point: 184-185 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 8.42 (d, J = 8.3 Hz, 2H), 8.14 (d, J= 8.7 Hz,1H), 7.94 – 7.88 (m, 1H), 7.81 (d, J = 8.2 Hz, 1H), 7.66 – 7.60 (m, 1H), 7.55 –7.51 (m, 1H), 7.34 – 7.26 (m, 1H), 4.46 (s, 3H), 3.91 (d, J = 10.2 Hz, 1H), 3.68 (s, 1H), 2.15 (s, 1H), 1.91 (d, J = 5.2 Hz, 2H), 1.21 (s, 1H), 0.85 (s, 1H); 13 C NMR (100 MHz, DMSO- d 6 ) d 147.5, 142.5, 139.1, 134.4, 132.2, 129.9,128.1, 124.1, 122.0, 120.8, 119.6, 116.8, 116.5, 114.7, 114.2, 63.9, 53.8,50.8, 38.5, 33.8; HRMS (ESI), calculated value C 20 H 21 N 4 + [M] + 317.1761, experimental measurement value 317.1761.

[0045] 24-Chenylpyruvate derivatives : Yellow solid, melting point: 245-246 °C; 1 H NMR (400 MHz, DMSO- d 6 ) δ 8.74 (d, J = 8.3 Hz, 1H), 8.52 (d, J = 7.9 Hz,1H), 8.33 (d, J = 8.8 Hz, 1H), 8.00 (t, 1H), 7.86 (d, J= 8.3 Hz, 1H), 7.73 –7.62 (m, 2H), 7.31 (t, 1H), 5.05 (s, 1H), 4.60 (s, 3H), 3.49 – 3.39 (m, 1H),3.33 (d, J = 11.9 Hz, 2H), 3.10 (t, J = 11.7 Hz, 2H), 2.22 – 2.13 (m, 2H), 1.96 –1.88 (m, 2H); 13 C NMR (100 MHz, DMSO) δ 148.0, 147.5, 137.3, 137.2, 131.6, 130.8,126.7, 125.0, 124.2, 119.8, 119.7, 118.0, 115.9, 114.7, 51.7, 47.7, 43.7,31.5; HRMS (ESI), calculated value C 21 H 23 N 4 + [M] + 331.1917, experimental measurement value 331.1919.

[0046] 25 : Yellow solid, melting point: 217-218 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 8.77 (d, J = 8.5 Hz, 1H), 8.53 (d, J = 8.4 Hz,1H), 8.33 (d, J = 8.9 Hz, 1H), 8.03 – 7.97 (m, 1H), 7.85 (d, J = 8.4 Hz, 1H),7.68 (t, J = 6.9 Hz, 2H), 7.32 (t, J = 7.6 Hz, 1H), 4.60 (s, 3H), 4.15 (d, J = 6.8Hz, 2H), 3.24 (d, J= 12.4 Hz, 2H), 2.76 (t, J = 11.7 Hz, 2H), 2.13 (s, 1H), 1.95(d, J = 12.3 Hz, 2H), 1.53 – 1.40 (m, 2H); 13 C NMR (100 MHz, DMSO- d 6 ) d 144.3, 137.5, 135.8, 132.4, 130.3, 124.6,124.5, 124.1, 120.6, 118.8, 118.2, 116.6, 115.7, 115.1, 114.9, 50.4, 43.6,38.4, 35.1, 27.1; HRMS (ESI), calculated value C 22 H 25 N 4 + [M] + 345.2074, experimental measurement value 345.2073.

[0047] 26-Method of the derivatives of leucophylla : Yellow solid, melting point: 200-201 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 8.92 (s, 1H), 8.72 (d, J = 8.4 Hz, 1H), 8.54(d, J = 8.4 Hz, 1H), 8.35 (d, J = 8.9 Hz, 1H), 8.07 – 7.98 (m, 1H), 7.88 (d, J =8.3 Hz, 1H), 7.79 – 7.67 (m, 2H), 7.43 – 7.33 (m, 1H), 4.60 (s, 3H), 4.20 (s,1H), 4.11 – 3.90 (m, 2H), 3.18 (d, J= 11.9 Hz, 2H), 2.92 – 2.79 (m, 2H), 2.32(s, 1H), 2.00 – 1.79 (m, 2H), 1.61 – 1.34 (m, 2H); 13 C NMR (100 MHz, DMSO- d 6 ) d 144.1, 137.5, 136.2, 132.7, 132.7, 131.0,124.8, 124.5, 124.4, 121.1, 117.9, 115.7, 115.0, 114.4, 100.0, 47.9, 46.3,44.0, 38.6, 34.5, 26.1, 21.6; HRMS (ESI), calculated value C 22 H 25 N 4 + [M] + 345.2074, experimental measurement value 345.2074.

[0048] 27 : Yellow solid, melting point: 240-241 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 11.90 (s, 1H), 8.74 (d, J = 8.1 Hz, 1H), 8.55(d, J = 8.1 Hz, 1H), 8.36 (d, J = 8.3 Hz, 2H), 8.04 (t, J = 7.5 Hz, 1H), 7.93 (d, J =8.1 Hz, 1H), 7.81 – 7.68 (m, 2H), 7.39 (t, J = 7.2 Hz, 1H), 4.86 (s, 1H), 4.62(s, 3H), 3.28 – 3.15 (m, 4H), 2.77 (s, 3H), 2.29 – 2.08 (m, 4H); 13 C NMR (100 MHz, DMSO-d 6 ) d 143.4, 143.3, 137.5, 136.7, 132.9, 131.4,125.0, 124.6, 121.5, 117.9, 117.4, 116.2, 115.2, 114.1, 54.9, 52.6, 50.1,38.8, 30.4; HRMS (ESI), calculated value C 22 H 25 N 4 + [M] + 345.2074, experimental measurement value 345.2074.

[0049] 28-Citrine derivatives : Yellow solid, melting point: 246-247 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 11.83 (s, 1H), 8.86 (s, 1H), 8.77 (d, J = 8.6Hz, 1H), 8.60 (d, J = 8.6 Hz, 1H), 8.39 (d, J = 9.0 Hz, 1H), 8.05 (t, 1H), 7.89(d, J = 8.4 Hz, 1H), 7.81 – 7.72 (m, 2H), 7.41 (t, J = 7.7 Hz, 1H), 4.65 (s, 3H), 4.07 (s, 2H), 3.11 (s, 5H), 2.70 (s, 3H), 2.16 – 1.96 (m, 3H), 1.63 – 1.47(m, 2H); 13 C NMR (100 MHz, DMSO- d 6 ) d144.1, 143.3, 137.7, 136.3, 132.9, 131.2,124.9, 124.7, 124.4, 121.4, 118.0, 117.0, 115.8, 115.1, 114.1, 54.9, 49.9,43.1, 38.6, 34.0, 27.2; HRMS (ESI), calculated value C 23 H 27 N 4 + [M] + 359.2230, experimental measurement value 359.2229.

[0050] 29 : Yellow solid, melting point: 177-178 °C; 1 H NMR (400 MHz, DMSO- d 6 ) d 8.68 (d, J = 8.5 Hz, 1H), 8.53 (d, J = 8.4 Hz,1H), 8.32 (d, J = 8.9 Hz, 1H), 8.00 (t, 1H), 7.79 (d, J = 8.3 Hz, 1H), 7.70 (t, J =7.6 Hz, 2H), 7.35 (t, J = 7.6 Hz, 1H), 4.57 (s, 3H), 4.50 (s, 1H), 3.69 (d, J =15.0 Hz, 1H), 2.47 – 2.33 (m, 2H), 2.31 – 2.22 (m, 1H), 2.08 (s, 3H), 1.86 –1.78 (m, 1H), 1.76 – 1.67 (m, 1H), 1.66 – 1.56 (m, 1H), 1.54 – 1.43 (m, 1H), 1.27 – 1.18 (m, 1H), 0.88 – 0.79 (m, 1H); 13 C NMR (100 MHz, DMSO- d 6 ) d144.8, 143.9, 137.5, 136.3, 132.6, 130.8,124.7, 124.4, 124.1, 120.9, 117.8, 115.6, 115.5, 114.4, 55.5, 47.8, 45.8,38.4, 35.1, 26.3, 22.4, 14.4; HRMS (ESI), calculated value C 23 H 27 N 4 + [M] + 359.2230, experimental measurement value 359.2231.

[0051] Example 2 Determination of the insecticidal activity of cephalosporin and its derivatives against root-knot nematodes.

[0052] 1. Treat the plants and their roots: Pull up tomato plants that have grown for more than 60 days from the greenhouse and wash the roots with water to remove the soil; 2. Collect eggs: Use a needle to pick up the root-knot nematode egg capsules from the roots, place them in a small petri dish containing 5 mL of distilled water, and incubate them in a 27°C incubator for 2 to 3 days to collect the second-instar larvae. Concentrate the collected larvae into a nematode suspension; 3. Preparation of compound solutions: All test compounds were dissolved in dimethyl sulfoxide (DMF) to a final concentration of 0.5% and diluted with 1% Tween 80; Among them, avermectin served as a positive control, while the test solution without the compound served as a negative control; 4. Determination of insecticidal activity: Add the test solution of the required concentration into a 48-well biochemical culture dish, ensuring that three replicates are set for each test compound; then add about 200 nematodes to each well; use a binocular microscope to observe the death of the nematodes after 72 hours.

[0053] The corrected mortality rate of nematodes can be calculated using the following formula: Corrected mortality % = [(% mortality of treatment group −% mortality of negative control group) / (1 −% mortality of negative control group)] × 100. The test results of the root-knot nematode killing activity of different compounds are shown in Table 1.

[0054] From the data provided in Table 1, it can be seen that leucophylline and its derivatives all show good activity in killing root-knot nematodes and are expected to be used in the prevention and treatment of plant nematodes. Among them, at a concentration of 100 mg / L, leucophylline derivative 14, leucophylline derivative 15, leucophylline derivative 17, leucophylline derivative 20, leucophylline derivative 22, and leucophylline derivative 23 all have insecticidal activities greater than 80%.

[0055] Example 3 Determination of the insecticidal activity of cephalosporin and its derivatives against Caenorhabditis elegans.

[0056] According to the method disclosed in the reference (Tang Xiaoming et al., Study on the Antioxidant Effect of Coumarin on Caenorhabditis elegans, Changchun University of Science and Technology, 2012), the second instar larvae of Caenorhabditis elegans for activity test were obtained.

[0057] The commercial agent thiathiophene was used as the positive control, and clean water was used as the blank control.

[0058] The insecticidal activity of the target compound against Caenorhabditis elegans was determined according to the toxicity method disclosed in the reference (Nadhem A, Urgeghe PP, Oplos C, et al. Nematicidal Activity of the Volatilome of Eruca sativa on Meloidogyne incognita [J]. JAgric Food Chem, 2015, 63, 6120.). Each compound was tested in triplicate and repeated three times, and the death of nematodes was counted 72 hours after application.

[0059] Calculate the corrected mortality of nematodes using the following formula: Corrected mortality % = [(% mortality in treatment group −% mortality in negative control group) / (1 −% mortality in negative control group)] × 100. The test results of the C. elegans killing activity of different compounds are shown in Table 2.

[0060] From the data provided in Table 2, it can be seen that leucine and its derivatives all show good activity in controlling Caenorhabditis elegans and are expected to be used in the control of animal nematodes. Among them, at 200 mg / L, the insecticidal activity of compounds leucine derivative 9, leucine derivative 15, leucine derivative 17, leucine derivative 20, leucine derivative 22, leucine derivative 23, and leucine derivative 25 are all greater than 80%.

[0061] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. The use of cephalaenopsis alkaloids and their derivatives in controlling nematodes, characterized in that: Includes the control of plant nematodes and / or animal nematodes.

2. The use of cephalaenopsis linalool and its derivatives in controlling nematodes as claimed in claim 1, characterized in that: The plants include crops and / or flowers.

3. The use of cephalaenopsis linalool and its derivatives in controlling nematodes as claimed in claim 2, characterized in that: The crops include one or more of tomatoes, eggplants, bitter melons, cucumbers, melons, loofahs, celery, peppers, cowpeas, kidney beans, potatoes, tobacco, beets, Chinese cabbage, cauliflower, kale, radishes, carrots, onions, garlic, rapeseed, citrus, grapes, bananas, pineapples, passion fruit, strawberries, pitaya and kiwi fruit.

4. The use of cephalaenopsis linalool and its derivatives in controlling nematodes as claimed in claim 2, characterized in that: The flowers include one or more of lily, rose, carnation, cactus, daffodil, hyacinth, ginger flower, gerbera, water lily, lotus and cattail.

5. The use of cephalaenopsis linalool and its derivatives in controlling nematodes according to claim 1, characterized in that: The plant nematodes include one or more of root-knot nematodes, stem nematodes, leaf nematodes, cyst nematodes, root-rot nematodes, reniform nematodes, semi-penetrating nematodes and pine wood nematodes.

6. The use of cephalaenopsis linalool and its derivatives in controlling nematodes according to claim 1, characterized in that: The animal nematodes include Caenorhabditis elegans.

7. The use of cephalaenopsis linalool and its derivatives in controlling nematodes according to claim 1, characterized in that: The structural formula of cephalaenopsis alkaloids is shown below: 。 8. The use of cephalaenopsis linalool and its derivatives in controlling nematodes according to claim 1, characterized in that: The derivatives of leucoderma alkaloids are selected from any one or more of the following structural formulas: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 。 9. The use of cephalaenopsis linalool and its derivatives in controlling nematodes according to claim 1, characterized in that: The application includes preparing pesticides with cephalaline and / or cephalaline derivatives as active ingredients.

10. The use of cephalaenopsis linalool and its derivatives in controlling nematodes according to claim 1, characterized in that: The application includes preparing veterinary drugs with cephalaline and / or cephalaline derivatives as active ingredients.

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