Application of sesquiterpene laurene and its derivatives in prevention and treatment of plant virus and bacterial diseases

Abstract

The application relates to application of a sesquiterpene laurene and derivatives thereof in treating plant virus and bacteria diseases, and discloses that the sesquiterpene laurene and derivatives I-1-I-19 thereof are found to have good activity against plant viruses and bacteria for the first time, and can well inhibit eight kinds of plant bacteria including tobacco mosaic virus (TMV) and cucumber fusarium, peanut brown spot, apple ring, wheat sharp eyespot, tomato early blight, rice blast, pepper phytophthora and rape sclerotinia.

Description

TECHNICAL FIELD

[0001] The present application relates to the application of sesquiterpene laurene and its derivatives in treating plant virus and pathogenic fungi, belonging to the technical field of agricultural protection. BACKGROUND

[0002] Laurene (reaction formula one) is a sesquiterpene containing 1, 2, 3 substituted cyclopentene structure, mainly existing in marine red algae. In 1965, Irie group of Hokkaido University in Japan (Tetrahedron Lett. 1965, 6, 3619-3624.) first isolated laurene from the metabolites of marine red algae Laurencia glandulifera. In 2012, Ji group of Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences (Fitoterapia. 2012, 83, 518-522.) isolated sesquiterpene laurene from marine red algae Laurencia okamurai.

[0003]

[0004] In 1973, McMurry group of University of California realized the total synthesis of natural product laurene from cyclohexanone as starting material through 11-step reaction (Tetrahedron. 1974, 30, 2027-2032.), with total yield of 5.54% (reaction formula one). The reaction route is long and the total yield is low. In 1989, Srikrishna group of Indian Institute of Science, Bangalore (Tetrahedron Lett. 1989, 30, 3561-3562.) completed the total synthesis of natural product (±)-laurene through free radical cyclization from 1-(p-tolyl)propan-1-one as starting material through 6-step reaction, with total yield of 15.3% (reaction formula two). In 1995, Bailey group of University of Connecticut realized the construction of five-membered ring through 5-exo cyclization of organolithium, and realized the synthesis of natural products laurene and epilaurene through this scheme (J. Org. Chem. 1995, 60, 6511-6514.), which was completed through five steps with total yield of 38.7% (reaction formula three).

[0005]

[0006] Sesquiterpenes have a wide range of biological activities, and the detailed biological properties of laurene compounds remain to be studied, but other similar sesquiterpenes, such as cuparenes and herbertenes, have been found to be effective antifungal, antibiotic, neurotrophic and anti-lipid peroxidation drugs. So far, there has been no report on the use of sesquiterpenes to prevent and treat plant viral and bacterial diseases. SUMMARY

[0007] The present application provides the use of sesquiterpene derivatives in the prevention and treatment of plant viral and bacterial diseases. The sesquiterpene derivatives of the present application have good activity against plant viruses and bacteria.

[0008] The sesquiterpene derivatives of the present application are I-1 to I-19.

[0009]

[0010] Compared with the prior art, the present application first discovers that sesquiterpene derivatives I-1 to I-19 exhibit good activity against plant viruses and bacteria, and can effectively inhibit tobacco mosaic virus (TMV) and cucumber fusarium, peanut brown spot, apple ring, wheat pattern, tomato early epidemic, rice blast, pepper pythium, and 8 kinds of plant bacteria. DETAILED DESCRIPTION

[0011] In the present application, sesquiterpene derivatives I-1, I-2, I-11, and I-22 are prepared according to the following reference: Tetrahedron Lett. 2019, 60, 150941-150941. I-3 is prepared according to the following reference: Synlett. 2017, 28, 2829-2832. I-4 is prepared according to the following reference: Org. Biomol. Chem. 2014, 12, 5883-5890. I-5 is prepared according to the following reference: Tetrahedron Lett. 1997, 38, 4069-4070. I-6 and I-7 are prepared according to the following reference: J Chem. Soc., Perkin Trans. 1 1997, 21, 3127-3128. I-8 and I-9 are prepared according to the following reference: Tetrahedron Asymmetry 1993, 4, 27-30. I-10 and I-19 are prepared according to the following reference: Synthesis 1998, 5, 771-774. I-13 to I-15 are prepared according to the following reference: Tetrahedron 2012, 68, 7598-7604. I-16 to I-18 are prepared according to the following reference: Angew. Chem. 2014, 126, 5658-5661.

[0012] Example 1: Experimental data of sesquiterpene derivatives I-1 ~ I-19

[0013] I-1: colorless oil. 1 H NMR (400 MHz, CDC13) (for 2 = 1 inseparable mixture of diastereomers) δ 7.31-7.26 (m, 2H, ArH), 7.18 (d, J = 8.0 Hz, 2H, ArH), 7.13 (d, J = 8.0 Hz, 1H, ArH), 7.08-7.04 (m, 1H, ArH), 2.59 (dd, J = 6.9, 0.8 Hz, CHCH3), 2.49-2.39 (m, 3H, COCH2CH2), 2.34 (s, 3H, ArCH3), 2.32 (s, 1.5H, ArCH3), 2.16-2.05 (m, 3H, COCH2CH2), 1.40 (s, 1.5H, CCH3), 1.19 (s, 3H, CCH3), 1.03 (d, J = 7.0 Hz, 3H, CHCH3), 0.82 (d, J = 7.3 Hz, 1.5H, CHCH3). 13 C NMR (100 MHz, CDC13) δ 220.2, 144.4, 135.9, 129.7, 129.2, 129.1, 126.6, 125.4, 120.4, 115.4, 55.3, 54.4, 46.4, 45.8, 36.4, 35.2, 35.1, 32.2, 29.9, 20.9, 20.6, 11.9, 8.7. HRMS (EI): Cacld for C 14 H 18 O[M] + 202.1352, found 202.1358.

[0014] I-2: yellow liquid. 1H NMR (400 MHz, CDC13) δ 7.07 (d, J = 7.7 Hz, 1.35H, ArH), 6.76 (m, 1.7H, ArH), 6.68 (s, 1H, ArH), 3.83 (s, 1H, OCH3), 3.77 (s, 3H, OCH3), 3.04 (d, J = 7.0 Hz, 0.3H, CHCH3), 2.71 (q, J = 7.5 Hz, 1H, CHCH3), 2.40 (m, 3H, 2COCH2CH2+ 1ArCH3), 2.34 (s, 4H, 3ArCH3+ 1COCH2CH2), 2.29 (q, J = 6.0 Hz, 1H, COCH2CH2), 2.13-2.06 (m, 1H, COCH2CH2), 1.33 (s, 3H, CCH3), 1.22 (s, 1H, CCH3), 1.03 (d, J = 7.0 Hz, 1H, CHCH3), 0.69 (d, J = 7.5 Hz, 3H, CHCH3). 13 C NMR (100 MHz, CDC13) δ 223.3, 221.3, 158.1, 157.0, 137.7, 137.5, 131.8, 131.6, 126.9, 126.88, 121.2, 121.0, 112.7, 111.6, 55.0, 54.7, 53.5, 51.9, 45.7, 45.5, 35.1, 34.7, 32.7, 32.2, 27.1, 21.3, 19.9, 13.1, 9.4. HRMS (EI): C 15 H 20 O2[M] + 232.1458, found 232.1462.

[0015] I-3: yellow liquid. 1 H NMR (400 MHz, CDC13) δ 7.20-7.11 (m, 4H, ArH), 2.77 (td, J = 12.0, 5.6 Hz, 1H, CHCH3), 2.58-2.47 (m, 1H, CHAr), 2.35 (s, 3H, ArCH3), 2.34-2.16 (m, 3H, CH2CH2CO), 2.01-1.85 (m, 1H, CH2CH2CO), 1.03 (d, J = 6.9 Hz, 3H, CHCH3). 13C NMR (100 MHz, CDC13) δ 220.0, 139.3, 136.5, 129.4, 127.0, 51.4, 50.6, 37.8, 29.7, 21.1, 12.2. HRMS (EI): Calcd for C 13 H 16 O[M] + 188.1196, found 188.1199.

[0016] I-4: White solid, m.p. 76-77 °C. 1 H NMR (400 MHz, CDC13) δ 7.21-7.12 (m, 4H, ArH), 2.63 (d, J = 17.7 Hz, 1H, COCH2C), 2.45 (d, J = 11.2 Hz, 1H, COCH2C), 2.43-2.34 (m, 2H, CH2CH2CO), 2.33 (s, 3H, ArCH3), 2.30-2.21 (m, 2H, CH2CH2CO), 1.37 (s, 3H, CCH3). 13 C NMR (100 MHz, CDC13) δ 218.8, 145.58, 135.9, 129.3, 125.4, 52.4, 43.5, 36.6, 35.9, 29.5, 20.9. HRMS (EI): Calcd for C 13 H 16 O[M] + 188.1196, found 188.1202.

[0017] I-5: Yellow liquid. 1 H NMR (400 MHz, CDC13) δ 7.31 (d, J = 8.3 Hz, 2H, ArH), 7.19 (d, J = 8.0 Hz, 2H, ArH), 2.76-2.64 (m, 1H, CH2CH2CO), 2.56-2.44 (m, 2H, CH2CH2CO), 2.37 (s, 3H, ArCH3), 1.94 (ddd, J = 12.6, 8.8, 1.9 Hz, 1H, CH2CH2CO), 1.29 (s, 3H, CCH3), 1.20 (s, 3H, CCH3), 0.64 (s, 3H, ArCCH3). 13 C NMR (100 MHz, CDC13) δ 222.6, 142.0, 135.9, 129.0, 126.4, 53.2, 48.4, 33.8, 29.7, 25.4, 22.2, 20.9, 18.5. HRMS (EI): Calcd for C 15 H20 O[M] + 216.1509, found 216.1513.

[0018] I-6: colorless oily liquid. 1 H NMR (400 MHz, CDC13) (for 2:1 inseparable mixture of diastereomers) δ 7.35-7.30 (m, 2H, ArH), 7.20-7.15 (m, 2H, ArH), 7.14 (s, 1H, ArH), 4.96 (dd, J = 3.0, 1.9 Hz, 1H, CCH2), 4.93-4.89 (m, 1H, CCH2), 4.87 (d, J = 2.1 Hz, 1H, CCH2), 2.74 (dd, J = 6.1, 2.8 Hz, 1H, CHCH3), 2.61 (d, J = 7.1 Hz, 0.5H, CHCH3), 2.58-2.54 (m, 2H, CH2CCH2CH2), 2.52-2.43 (m, 1H, CH2CCH2CH2), 2.36 (d, J = 6.3 Hz, 4.5H, ArCH3), 2.27 (dt, J = 12.6, 9.0 Hz, 0.5H, CH2CCH2CH2), 1.98 (dt, J = 20.9, 10.4 Hz, 1H, CH2CCH2CH2), 1.87-1.82 (m, 0.5H, CH2CCH2CH2), 1.82-1.74 (m, 1H, CH2CCH2CH2), 1.31 (s, 1.5H, CCH3), 1.12 (s, 3H, CCH3), 0.96 (d, J = 6.7 Hz, 3H, CHCH3), 0.74 (d, J = 7.1 Hz, 1.5H, CHCH3). 13 C NMR (100 MHz, CDC13) δ 157.5, 156.6, 145.4, 144.5, 135.1, 134.8, 128.9, 128.7, 126.9, 125.9, 105.6, 105.1, 50.5, 49.0, 48.6, 47.8, 40.0, 34.7, 29.7, 29.2, 20.9, 19.0, 17.3, 11.8. HRMS (EI): Cacld for C 15 H 20 [M] + 200.1560, found 200.1563.

[0019] I-7: yellow liquid. 1H NMR (400 MHz, DMSO-d6) δ 6.90 (d, J = 7.8 Hz, 1H, ArH), 6.70 (s, 1H, ArH), 6.61 (dd, J = 7.7, 0.7 Hz, 1H, ArH), 4.87 (s, 1H, CCH2), 4.77 (d, J = 1.2 Hz, 1H, CCH2), 3.70 (s, 3H, OCH3), 2.92 - 2.82 (m, 1H, CHCH3), 2.33 (td, J = 9.8, 2.3 Hz, 2H, CH2CCH2CH2), 2.20 (s, 3H, ArCH3), 2.08 (ddd, J = 26.5, 12.8, 7.6 Hz, 1H, CH2CCH2CH2), 1.72 - 1.64 (m, 1H, CH2CCH2CH2), 1.03 (s, 3H, CCH3), 0.47 (t, J = 9.6 Hz, 3H, CHCH3). 13 C NMR (100 MHz, DMSO-d6) δ 158.3, 157.4, 136.8, 132.8, 127.7, 121.3, 112.4, 106.8, 55.5, 48.7, 48.4, 34.6, 28.0, 26.3, 21.3, 20.0. HRMS (EI): C 16 H 22 O[M] + 230.1666, found 230.1673.

[0020] I-8: colorless oily liquid. 1 H NMR (400 MHz, CDCl3) δ 7.11 (dt, J = 15.1, 5.2 Hz, 4H, ArH), 2.31 (s, 3H, ArCH3), 2.30 - 2.25 (m, 2H, CH3CCH2CH2), 1.91 (ddd, J = 14.9, 7.8, 6.5 Hz, 2H, CH3CCH2CH2), 1.72 - 1.70 (m, 3H, CCH3), 1.39 (s, 3H, CCH3), 1.37 (dt, J = 3.0, 1.0 Hz, 3H, CCH3). 13 C NMR (100 MHz, CDCl3) δ 146.3, 137.9, 134.8, 131.9, 128.8, 126.2, 54.6, 41.6, 35.9, 24.3, 21.0, 14.4, 10.4. HRMS (EI): C 15 H 20 [M] + 200.1560, found 200.1567.

[0021] I-9: white oil solid, melting point: 55-57 °C. 1 H NMR (400 MHz, CDC13) δ 6.89 (d, J = 7.7 Hz, 1H, ArH), 6.68 (s, 1H, ArH), 6.65 (d, J = 7.8 Hz, 1H, ArH), 3.77 (s, 3H, OCH3), 2.31 (s, 3H, ArCH3), 2.28-2.20 (m, 1H, CH3CCH2CH2), 2.16 (d, J = 7.0 Hz, 2H, CH3CCH2CH2), 1.76-1.70 (m, 1H, CH3CCH2CH2), 1.69 (s, 3H, CCH3), 1.49 (d, J = 8.3 Hz, 3H, CCH3), 1.43 (s, 3H, CCH3). 13 C NMR (100 MHz, CDC13) δ 158.4, 136.8, 133.3, 131.7, 127.8, 120.5, 112.7, 55.2, 53.9, 38.5, 35.9, 25.3, 21.3, 14.4, 11.1. HRMS (EI): Calcd for C 15 H 20 [M] + 200.1560, found 200.1567.

[0022] I-10: yellow oily liquid. 1H NMR (400 MHz, DMSO-d6) (for 3:0.7 inseparable mixture of diastereomers) δ 9.11 (s, 1H, OH), 8.91 (s, 0.3H, OH), 6.90 (t, J = 6.0 Hz, 1H, ArH), 6.73 (d, J = 7.8 Hz, 0.3H, ArH), 6.59 (d, J = 1.0 Hz, 1H, ArH), 6.57 (d, J = 1.2 Hz, 0.3H, ArH), 6.53 (dd, J = 7.7, 0.9 Hz, 1H, ArH), 6.44 (dd, J = 4.9, 0.9 Hz, 0.3H, ArH), 4.94 (s, 1H, CH2), 4.83 (s, 1H, CH2), 3.02 (q, J = 7.1 Hz, 1H, CHCH3), 2.59 (d, J = 7.4 Hz, 0.2H, CHCH3), 2.39 (dd, J = 9.8, 7.8 Hz, 2H, CH2CH2CCH2), 2.31 - 2.23 (m, 0.5H, CH2CH2CCH2), 2.18 (s, 3H, ArCH3), 2.16 (s, 1H, ArCH3), 1.90 - 1.68 (m, 2H, CH2CH2CCH2), 1.52 (d, J = 6.8 Hz, 0.5H, CH2CH2CCH2), 1.33 (s, 0.7H, CCH3), 1.13 (s, 3H, CCH3), 0.67 (d, J = 6.8 Hz, 0.7H, CHCH3), 0.62 (d, J = 7.2 Hz, 3H, CHCH3). 13 C NMR (100 MHz, DMSO-d6) δ 158.6, 156.0, 155.3, 137.3, 136.2, 131.1, 130.4, 127.9, 125.2, 121.0, 120.0, 119.4, 117.2, 116.5, 115.6, 106.6, 85.1, 53.7, 48.6, 48.2, 34.5, 28.1, 26.0, 21.0, 20.9, 20.1, 14.7, 11.5, 7.8. HRMS (ESI): C 15 H 19 O[M-H] - 215.1441, found 215.1446.

[0023] I-11: yellow oil liquid. 1H NMR (400 MHz, DMSO-d6) (for 3:2:1 inseparable mixture of diastereomers) δ 7.22-7.19 (m, 2H, ArH), 7.15 (d, J = 8.2 Hz, 1H, ArH), 7.09-7.06 (m, 4H, ArH), 4.68 (d, J = 5.6 Hz, 0.3H, OH), 4.65 (d, J = 5.0 Hz, 0.5H, OH), 4.47 (d, J = 4.0 Hz, 1H, OH), 4.14-4.07 (m, 1H, CHOH), 3.82-3.72 (m, 0.3H, CHOH), 3.60-3.50 (m, 0.5H, CHOH), 2.25 (s, 6H, ArCH3), 2.18-1.92 (m, 4H, CH2CHCHCH2CH2), 1.89-1.77 (m, 3H, CH2CHCHCH2CH2), 1.70-1.52 (m, 3H, CH2CHCHCH2CH2), 1.35 (s, 1.5H, CCH3), 1.24 (s, 3H, CCH3), 1.19 (s, 1H, CCH3), 0.83 (d, J = 7.2 Hz, 3H, CHCH3), 0.53 (d, J = 7.0 Hz, 1.5H, CHCH3), 0.47 (d, J = 7.2 Hz, 1H, CHCH3). 13 C NMR (100 MHz, DMSO-d6) δ 148.1, 147.2, 146.1, 144.4, 134.5, 134.4, 134.2, 129.1, 129.0, 128.8, 128.6, 127.4, 127.3, 125.9, 125.8, 78.2, 74.2, 73.4, 52.7, 52.4, 49.5, 48.6 48.4, 47.3, 47.1, 46.6, 36.8, 34.5, 34.1, 32.9, 32.7, 31.4, 31.2, 29.8, 23.2, 22.0, 20.9, 20.8 8, 14.5, 12.5, 11.4, 9.8. HRMS (EI): C 14 H 20 O[M] + 204.1509, found 204.1516.

[0024] I-12: colorless liquid. 1H NMR (400 MHz, CDC13) δ 7.19-7.15 (m, 2H, ArH), 7.11 (d, J = 8.0 Hz, 2H, ArH), 5.50 (d, J = 1.5 Hz, IH, CHCH2), 2.32 (s, 3H, ArCH3), 2.31-2.28 (m, 2H, CHCH2), 2.09-1.94 (m, 2H, CH2C), 1.49 (dd, J = 3.7, 2.1 Hz, 3H, CHCCH3), 1.43 (s, 3H, ArCCH3). 13 C NMR (100 MHz, CDC13) δ 146.8, 145.5, 134.9, 128.8, 126.2, 125.2, 53.3, 43.3, 29.9, 24.1, 20.9, 13.1. HRMS (EI): Calcd for C 14 H 18 [M] + 186.1404, found 186.1407.

[0025] I-13: yellow oil liquid. 1 H NMR (400 MHz, CDC13) δ 7.19-7.15 (m, 2H, ArH), 7.11 (d, J = 8.0 Hz, 2H, ArH), 5.50 (d, J = 1.5 Hz, IH, CHCH2), 2.32 (s, 3H, ArCH3), 2.31-2.28 (m, 2H, CHCH2), 2.09-1.94 (m, 2H, CH2C), 1.49 (dd, J = 3.7, 2.1 Hz, 3H, CHCCH3), 1.43 (s, 3H, ArCCH3). 13C NMR (100 MHz, CDC13) δ 158.9, 137.9, 133.4, 131.0, 127.1, 122.8, 122.6, 120.9, 120.7, 111.7, 109.8, 109.38, 101.0, 98.9, 55.4, 54.1, 46.2, 42.6, 41.2, 38.5, 31.2, 30.4, 24.1, 23.6, 21.5, 20.1, 17.6, 15.4, 13.2. HRMS (EI): Cacld for C 15 H 20 O[M] + 216.1509, found 216.1513.

[0026] I-14: yellow oil liquid. 1 H NMR (400 MHz, CDC13) δ 7.17 (s, 1H, ArH), 6.61 (s, 1H, ArH), 2.33 (s, 3H, ArCH3), 1.89 (ddd, J = 16.0, 8.8, 4.1 Hz, 1H, CH2CH2CH), 1.82 - 1.72 (m, 1H, CH2CH2CH), 1.68 - 1.58 (m, 2H, CH2CH2CH), 1.30 (s, 3H, CCH3), 1.29 (s, 3H, CCH3), 1.20 - 1.15 (m, 1H, CHCH3), 1.13 (d, J = 6.7 Hz, 3H, CHCH3). 13 C NMR (100 MHz, CDC13) δ 158.2, 136.9, 136.2, 126.5, 113.7, 110.9, 99.8, 54.3, 46.0, 42.6, 31.2, 23.4, 23.2, 19.9, 13.1. HRMS (EI): Cacld for C 15 H 19 BrO[M] + 294.0614, found 294.0618.

[0027] I-15: colorless oil liquid. 1H NMR (400 MHz, CDC13) (for 6:1 inseparable mixture of diastereomers) δ 7.20 (s, 0.16H, ArH), 7.11 (s, IH, ArH), 2.51 (s, 0.5H, ArCH3), 2.49 (s, 3H, ArCH3), 1.86 (ddd, J = 9.7, 6.3, 2.7 Hz, 1.4H, CH2CH2CH), 1.77 (td, J = 12.6, 6.1 Hz, IH, CH2CH2CH), 1.68-1.56 (m, 2.3H, CH2CH2CH), 1.47 (s, 0.5H, CCH3), 1.34 (s, 3.5H, CCH3), 1.32 (s, 3H, CCH3), 1.20-1.06 (m, 4H, CHCH3), 0.75 (d, J = 6.8 Hz, 0.5H, CHCH3). 13 C NMR (100 MHz, CDC13) δ 156.0, 149.7, 136.0, 135.8, 130.7, 127.3, 125.4, 114.2, 114.0, 112.7, 104.9, 100.3, 86.8, 55.8, 46.2, 45.6, 42.5, 42.0, 37.5, 31.2, 23.7, 23.3, 23.0, 22.8, 20.5, 20.2, 13.2, 7.3. HRMS (EI): Calcd for C 15 H 18 Br2O [M] + 371.9719, found 371.9726.

[0028] I-16: yellow oil liquid. 1H NMR (400 MHz, CDC13) (for 3:1 inseparable mixture of diastereomers) δ 7.09 (d, J = 7.9 Hz, 0.3H, ArH), 6.98 (d, J = 7.7 Hz, 1H, ArH), 6.68 (d, J = 8.2 Hz, 0.3H, ArH), 6.64 (d, J = 7.0 Hz, 1H, ArH), 6.53 (d, J = 0.5 Hz, 1H, ArH), 6.23 (s, 0.3H, ArH), 2.28 (s, 1H, ArCH3), 2.25 (s, 3H, ArCH3), 2.15 (dt, J = 13.3, 9.5 Hz, 0.3H, OCCH2CH2), 2.05 (ddd, J = 14.3, 9.3, 7.3 Hz, 1H, OCCH2CH2), 1.90-1.85 (m, 1.3H, OCCH2CH2), 1.84-1.74 (m, 1.3H, OCCH2CH2), 1.70-1.61 (m, 1.3H, OCCH2CH2), 1.60-1.53 (m, 0.3H, CHCH3), 1.49 (q, J = 6.8 Hz, 1H, CHCH3), 1.43 (s, 1H, OCCH3), 1.39 (s, 3H, OCCH3), 1.38 (s, 1H, CCH3), 1.34 (s, 3H, CCH3), 1.29 (d, J = 14.3 Hz, 1H, CHCH3), 0.77 (d, J = 6.8 Hz, 3H, CHCH3). 13 C NMR (100 MHz, CDC13) δ 155.3, 153.0, 138.4, 137.9, 137.2, 135.8, 129.4, 127.5, 126.7, 124.8, 120.7, 120.6, 117.2, 115.8, 85.1, 53.3, 46.7, 44.8, 42.4, 37.8, 37.4, 36.1, 23.8, 23.2, 21.1, 20.9, 20.6, 14.7, 10.1, 7.5. HRMS (El): C 15 H 20 O[M] + 216.1509, found 216.1514.

[0029] I-17: yellow oil liquid. 1H NMR (400 MHz, CDC13) δ 7.19 (s, IH, ArH), 6.59 (s, IH, ArH), 2.28 (s, 3H, ArCH3), 2.03 (ddd, J = 14.3, 9.2, 7.3 Hz, IH, OCCH2CH2), 1.93-1.85 (m, 2H, OCCH2CH2), 1.83-1.75 (m, IH, OCCH2CH2), 1.66 (ddd, J = 11.8, 9.4, 5.1 Hz, IH, OCCH2CH2), 1.49-1.46 (d, J = 6.8 Hz, IH, CHCH3), 1.39 (s, 3H, OCCH3), 1.32 (s, 3H, CCH3), 0.76 (d, J = 6.8 Hz, 3H, CHCH3). 13 C NMR (100 MHz, CDC13) δ 152.4, 136.5, 130.2, 128.5, 117.5, 114.4, 85.5, 46.4, 44.9, 42.2, 37.3, 23.0, 22.5, 20.5, 7.4. HRMS (EI): Cacld for C 15 H 19 BrO[M] + 294.0614, found 294.0618.

[0030] I-18: white oil. 1 H NMR (400 MHz, CDC13) δ 7.19 (s, IH, ArH), 6.59 (s, IH, ArH), 2.28 (s, 3H, ArCH3), 2.03 (ddd, J = 14.3, 9.2, 7.3 Hz, IH, OCCH2CH2), 1.93-1.85 (m, 2H, OCCH2CH2), 1.83-1.75 (m, IH, OCCH2CH2), 1.66 (ddd, J = 11.8, 9.4, 5.1 Hz, IH, OCCH2CH2), 1.49-1.46 (d, J = 6.8 Hz, IH, CHCH3), 1.39 (s, 3H, OCCH3), 1.32 (s, 3H, CCH3), 0.76 (d, J = 6.8 Hz, 3H, CHCH3). 13C NMR (100 MHz, CDC13) δ 156.4, 149.7, 137.4, 135.8, 130.7, 127.3, 126.6, 115.0, 114.2, 112.7, 111.3, 102.8, 86.8, 78.1, 54.2, 46.2, 45.4, 42.2, 42.0, 40.9, 37.5, 29.6, 26.6, 24.0, 23.7, 23.2, 22.8, 20.5, 19.0, 7.3. HRMS (EI): calcd for C 15 H 18 Br2O[M] + 371.9719, found 371.9724.

[0031] I-19: yellow oil liquid. 1 H NMR (400 MHz, DMSO-d6) δ 6.97 (d, J = 7.8 Hz, 1H, ArH), 6.64-6.55 (m, 1H, ArH), 6.45 (s, 1H, ArH), 4.93 (t, J = 5.8 Hz, 1H, OH), 3.49 (d, J = 6.0 Hz, 2H, CH2OH), 2.18 (s, 3H, ArCH3), 2.09 (dd, J = 15.8, 9.9 Hz, 1H, CHCH3), 1.78-1.68 (m, 2H, OCCH2CH2), 1.68-1.56 (m, 2H, OCCH2CH2), 1.29 (s, 3H, CCH3), 0.64 (d, J = 6.8 Hz, 3H, CCH3). 13 CNMR (100 MHz, DMSO-d6) δ 152.2, 136.4, 127.8, 124.9, 120.6, 115.2, 87.2, 62.0, 44.1, 41.8, 41.0, 32.0, 20.4, 20.1, 7.3. HRMS (EI): calcd for C 15 H 20 O2[M] + 232.1458, found 232.1466.

[0032] Example 2: Determination of Anti-Tobacco Mosaic Virus Activity, the determination procedure is as follows:

[0033] 1. Virus purification and concentration determination:

[0034] The virus purification and concentration determination refer to the Tobacco Mosaic Virus SOP specification prepared by the Institute of Element Analysis of Nankai University. After the crude virus extract is treated by polyethylene glycol centrifugation twice, the concentration is determined, and it is stored at 4°C for standby.

[0035] 2. Preparation of compound solution:

[0036] After weighing, the original drug was dissolved in DMF to prepare 1 x 10 5 μg / mL stock solution, which was then diluted to the desired concentration with 1‰ Tween 80 aqueous solution; the ribavirin preparation was directly diluted with water.

[0037] 3. In vivo protection effect:

[0038] Select 3-5 leaf stage of uniform and consistent Xianxi tobacco, spray the whole plant, repeat 3 times per treatment, and set 1‰ Tween 80 aqueous solution as control. After 24 h, sprinkle corundum (500 mesh) on the leaf surface, use a brush to dip the virus solution, and gently rub the whole leaf surface along the vein direction twice, with the palm supporting under the leaf. The virus concentration is 10 μg / mL. After inoculation, rinse with running water. Record the number of lesions after 3 d, and calculate the control effect.

[0039] 4. In vivo treatment effect:

[0040] Select 3-5 leaf stage of uniform and consistent Xianxi tobacco, use a brush to inoculate the whole leaf with the virus, and the virus concentration is 10 μg / mL. After inoculation, rinse with running water. After the leaf surface is dry, spray the whole plant, repeat 3 times per treatment, and set 1‰ Tween 80 aqueous solution as control. Record the number of lesions after 3 d, and calculate the control effect.

[0041] 5. In vivo inactivation effect:

[0042] Select 3-5 leaf stage of uniform and consistent Xianxi tobacco, mix the drug with an equal volume of virus juice for 30 min, then rub and inoculate, and the virus concentration is 20 μg / mL. After inoculation, rinse with running water immediately. Repeat 3 times, and set 1‰ 0 Tween 80 aqueous solution as control. Count the number of lesions after 3 d, and calculate the results.

[0043] Inhibition rate (%) = [(control dead spots - treatment dead spots) / control dead spots] x 100%

[0044] First, test the in vivo inactivation activity of all compounds against tobacco mosaic virus at a treatment dose of 500 μg / mL. Further test the in vivo treatment and in vivo protection activities of the compounds with a relative inhibition rate greater than 40% at a treatment dose of 500 μg / mL, and test the in vivo inactivation, in vivo treatment, and in vivo protection activities against tobacco mosaic virus at a treatment dose of 100 μg / mL. The positive control is the commercial anti-plant virus drug ribavirin.

[0045] Table 1 Test results of sesquiterpene laurene derivatives I-1-I-19 against tobacco mosaic virus (TMV)

[0046]

[0047]

[0048] From the data in Table 1, it can be seen that the sesquiterpene laurene derivatives I-1 to I-19 all exhibit good anti-TMV activity. At 500 μg / mL, the activity of 7 compounds is comparable to that of the virus azole, which has great development value.

[0049] Example 3: Anti-bacterial activity test, the determination procedure is as follows:

[0050] In vitro bactericidal test, bacterial growth rate determination method (plate method):

[0051] A certain amount of medicament was dissolved in an appropriate amount of acetone, then diluted to the required concentration with 200 μg / mL emulsifier aqueous solution, then 1 mL of each drug solution was injected into the culture dish, and 9 mL of culture medium was added, then shaken to prepare a 50 μg / mL drug-containing plate. The plate to which 1 mL of sterile water was added was used as a blank control. A punch with a diameter of 4 mm was used to cut the mycelium along the outer edge of the dish and transfer it to the drug-containing plate. Each treatment was repeated three times. The culture dishes were placed in a constant temperature incubator at 24±1°C for incubation. After 48 hours, the expansion diameter of each treatment dish was investigated, the average value was calculated, and the relative inhibition rate was calculated by comparison with the blank control.

[0052]

[0053] Table 2: In vitro bactericidal activity test results of sesquiterpene laurene derivatives I-1 to I-19:

[0054]

[0055] The sesquiterpene laurene derivatives exhibited broad-spectrum inhibitory activity against 8 tested bacteria at a test concentration of 50 μg / mL. The inhibition rate of compound I-10 on rice blast reached 80%. The inhibitory activity of some compounds on some strains was better than that of the commercial variety of bercil, which has great development value.

Claims

1. Use of sesquiterpenes laurones and their derivatives I-1 to I-4, I-6, I-9 to I-12, I-14, I-17 to I-19 for the control of tobacco mosaic virus disease.

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