CN116530514A - Application of cis-enamide derivative in preparation of antibacterial drugs - Google Patents

Application of cis-enamide derivative in preparation of antibacterial drugs Download PDF

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CN116530514A
CN116530514A CN202310481215.9A CN202310481215A CN116530514A CN 116530514 A CN116530514 A CN 116530514A CN 202310481215 A CN202310481215 A CN 202310481215A CN 116530514 A CN116530514 A CN 116530514A
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nmr
cdcl
cis
mhz
enamide
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姚宏亮
李刚
关文
童荣标
宋立彦
曾芷筠
欧扬慧
李嘉裕
何登芹
张亚莉
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Institute of Zoology of Guangdong Academy of Sciences
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P3/00—Fungicides
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Wood Science & Technology (AREA)
  • Environmental Sciences (AREA)
  • Pest Control & Pesticides (AREA)
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  • General Chemical & Material Sciences (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention discloses application of cis-enamide derivatives in preparation of antibacterial drugs. The chemical structure of the cis-enamide derivative is shown as any one of (a), wherein R is shown in the formula 1 Is hydrogen, methoxy, methyl, trifluoromethyl, benzo fused ring or halogen; r is R 2 Is methyl, methoxy, trifluoromethyl, benzofused ring or halogen. The cis-enamide derivative has a bacteriostatic action, and provides a pesticide with a new structure type for agricultural plant pathogenic fungi.

Description

Application of cis-enamide derivative in preparation of antibacterial drugs
Technical Field
The invention belongs to the field of biological medicine, and in particular relates to application of cis-enamide derivatives in preparation of antibacterial medicines.
Background
The individual parts of the yellow skin (Clausena lansium (lour.)) have long been traditional folk medicines. Lansium amide B, a wampee amide compound extracted from wampee seeds, has been widely studied by pharmaceutical and agrochemical chemists due to its diverse structures and biological activities, and is reported to have pharmacological activities such as anti-obesity and insulin sensitivity, anticonvulsant and antispasmodic, anti-inflammatory and anti-necrotic activities. And Lansium amide B has remarkable agricultural activities of killing insects, inhibiting bacteria and weeding.
Lansium amide B is a wampee amide compound extracted from wampee plants. Wampee (Clausena lansium (lour.)) is a member of the family Rutaceae (Rutaceae), a green shrub or small arbor, and is known as the name oilseed plum, cockscomb. Wampee (Clausena lansium) originates in the southern part of the continental china and is widely cultivated in the southern part of the continental china, southeast asia and north america due to its broad biological activity. The parts of the wampee have long been traditional folk medicinal materials, namely hunger eating litchi and satiating wampee. The folk likes to take wampee leaves for preventing and treating cold, bronchial asthma, gastrointestinal tract inflammation and abscess or wampee roots for treating qi pain. The pericarp and the pit of the wampee are also good materials for medicament, which are beneficial to promoting urination, detumescence, promoting qi circulation, relieving pain and the like. The wampee seeds are rich in oil, the oil yield is up to 42%, and the wampee seeds are excellent lubricants. The wampee is popular among customers as a high-quality fruit with a sweet and sour taste, and the wampee can be made into desserts such as fruit cups, gelatin and the like besides fresh food.
Disclosure of Invention
The invention aims to provide application of cis-enamide derivatives in preparation of antibacterial drugs.
The chemical structure of the cis-enamide derivative is shown as (a),
(a) Wherein R is 1 Is hydrogen, methoxy, methyl, trifluoromethyl, benzo fused ring or halogen, etc.;
R 2 methyl, methoxy, trifluoromethyl, halogen, etc.
The cis-enamide derivative is preferably one of the following compounds:
further preferably, the structural formula of the cis-enamide derivative is shown as any one of the following:
experiments show that the cis-enamide derivative can effectively inhibit plant pathogenic fungi, has good antibacterial activity, and can be used as a pesticide for treating plant pathogenic fungi infection.
Preferably, the cis-enamide derivative or the salt thereof is applied to the preparation of plant source antibacterial pesticides.
Preferably, the cis-enamide derivative or the salt thereof is applied to the preparation of anti-sclerotinia, rice sheath blight or botrytis cinerea.
The cis-enamide derivative has a bacteriostatic action, and provides a pesticide with a new structure type for agricultural plant pathogenic fungi.
Detailed Description
The following examples are further illustrative of the invention and are not intended to be limiting thereof.
The structural formula of the compound 2002-2046 is shown as the following formula:
example 1 synthesis of compound 2002-2018.
Synthesis of Compound 1:
250ml of two-neck flask, a magnet and an air suction head are put into an oven for drying in advance, the flask is installed, the vacuum pumping is carried out until the room temperature is reached, argon is replaced, iodoform (21 mmol) and triphenylphosphine (22 mmol) are rapidly weighed in, the vacuum pumping is carried out again, argon is replaced for three times, and anhydrous THF (80 ml) sucked by a long needle is pumped into the flask. t-BuOK (20 mmol) was added, after 1min, a solution of aromatic aldehyde derivative (10 mmol) in dry THF (15 ml) was added. After stirring at room temperature for 30min, the suspension was cooled to-78℃and t-BuOK (50 mmol) was added in portions. After 15 minutes, saturated saline was added dropwise to quench the solution, and the solution was allowed to slowly return to room temperature. Ethyl acetate (3 x 50 ml), the organic phases were combined, then dried over anhydrous sodium sulfate and finally the solvent was evaporated under reduced pressure. The crude liquid is purified by petroleum ether eluent and silica gel chromatographic column. Compound 1 was obtained.
Synthesis of Compound 2:
compound 1 (9.8 mmol) was weighed into a 100mL vial, magneton was added, THF (20 mL) and equal amounts of water were added, 4-methylbenzenesulfonyl hydrazide (19.6 mmol) and sodium acetate (29.4 mmol) were weighed into the vial, the stopper was screwed in,the reaction was heated under reflux in an oil bath. The reaction was monitored by TLC, after complete consumption of starting material (12 h), the oil bath was removed, the reaction mixture was cooled to room temperature, quenched with saturated aqueous ammonium chloride solution in ice bath, then Et 2 O (3X 20 mL) extraction, washing the organic phase with saturated aqueous sodium chloride solution, drying over anhydrous sodium sulfate. The organic phase is filtered off, the solvent is removed under reduced pressure and the residue is passed through a column. Purifying by using petroleum ether as an eluent to obtain the compound 2.
Synthesis of Compound 3:
schlenk tube was weighed into CuI (0.25 mmol,5 mol%), cs 2 CO 3 (7.5 mmol) and trans-cinnamamide (0.882 g,6.0 mmol), and argon was purged. DMEDA (0.50 mmol,10 mol%), compound 2 (5.0 mmol) and THF (10.0 ml) were added. The Schlenk tube was sealed and placed in an oil bath at 60 ℃ for reaction. After TLC analysis indicated complete consumption of starting material (3 h), the oil bath was removed and replaced with ice bath to cool down to room temperature. The solid was filtered off with celite and washed with ethyl acetate (50 ml). The solvent was removed by vacuum rotary evaporator to give the crude product. Petroleum ether/ethyl acetate (v/v=5:1) was used as eluent and compound 3 was obtained after column purification.
Synthesis of Compound 4:
to anhydrous DMF (15 mL) containing compound 3 (4.13 mmol) was added 60% NaH (24.78 mmol) at 0deg.C. After the reaction for 30min, methyl iodide (28.91 mmol) was added dropwise. After TLC analysis indicated complete consumption of starting material (2 h), water was slowly added dropwise to quench the reaction. The organics were extracted with ethyl acetate (3X 10 ml), the organics combined and washed with saturated brine then with anhydrous NaSO 4 Drying and finally evaporating the solvent under reduced pressure. The crude liquid is purified by a silica gel chromatographic column by using petroleum ether/ethyl acetate (v/v=10:1) as eluent to obtain the target compound 2002-2018.
2002:Yellowish oil. 1 H NMR(400MHz,CDCl 3 )δ:7.48(d,J＝15.6Hz,1H),7.45-7.43(m,2H),7.38-7.32(m,3H),7.22(dd,J＝7.6Hz,1H),7.18(td,J＝7.6,1.6Hz,1H),6.91(d,J＝15.6Hz,1H),6.88(t,J＝7.6Hz,1H),6.76(d,J＝7.6Hz,1H),6.50(d,J＝8.8Hz,1H),6.41(d,J＝8.8Hz,1H),3.75(s,3H),3.06(s,3H). 13 C{ 1 H}NMR(100MHz,CDCl 3 )δ:166.5,156.7,142.0,135.4,129.6,129.3,129.2,129.1,128.7(2×C),128.0(2×C),123.6,120.7,119.7,118.8,110.5,55.4,34.9.HRMS(ESI)m/z calculated for C 19 H 20 O 2 N + [M+H] + 294.1489,found,294.1493.
2003:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.62(d,J＝15.6 Hz,1H),7.47-7.44(m,2H),7.36-7.32(m,3H),7.21(t,J＝8.0 Hz,1H),6.92(d,J＝15.6 Hz,1H),6.91(d,J＝8.0 Hz,1H),6.85(s,1H),6.78(dd,J＝8.0,2.4 Hz,1H),6.49(d,J＝8.8 Hz,1H),6.21(d,J＝8.8 Hz,1H),3.74(s,3H),3.10(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:166.5,159.7,142.7,135.8,135.2,129.8,129.7,129.1,128.8(2×C),128.0(2×C),124.9,121.2,118.4,113.9,113.8,55.3,34.8.HRMS(ESI)m/z calculated for C 19 H 20 O 2 N + [M+H] + 294.1489,found 294.1493.
2004:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.65(d,J＝15.6 Hz,1H),7.46-7.43(m,2H),7.35-7.31(m,3H),7.28(d,J＝8.8 Hz,2H),6.95(d,J＝15.6 Hz,1H),6.83(d,J＝8.8 Hz,2H),6.37(d,J＝8.4 Hz,1H),6.20(d,J＝8.4 Hz,1H),3.77(s,3H),3.10(s,3H). 13 C{ 1 H}NMR(100MHz,CDCl 3 )δ:166.6,159.4,142.6,135.3,130.2(2×C),129.7,128.8(2×C),128.0(2×C),127.0,126.9,125.5,118.4,114.1(2×C),55.3,34.5.HRMS(ESI)m/z calculated for C 19 H 20 O 2 N + [M+H] + 294.1489,found 294.1499.
2005:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.59(d,J＝15.6 Hz,1H),7.51-7.49(m,2H),7.38-7.35(m,3H),7.23-7.20(m,1H),7.16-7.13(m,3H),6.92(d,J＝15.6 Hz,1H),6.65(d,J＝8.8 Hz,1H),6.22(d,J＝8.8 Hz,1H),2.94(s,3H),2.28(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:166.6,142.7,136.1,135.2,134.1,130.2,129.8,129.5,128.8(2×C),128.6,128.0(2×C),127.9,126.1,121.2,118.4,34.9,20.1.HRMS(ESI)m/z calculated for C 19 H 20 ON + [M+H] + 278.1539,found 278.1544.
2006:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.62(d,J＝15.6 Hz,1H),7.48-7.45(m,2H),7.37-7.33(m,3H),7.20(t,J＝7.6 Hz,1H),7.13(d,J＝7.6 Hz,1H),7.11(s,1H),7.04(d,J＝7.6 Hz,1H),6.93(d,J＝15.6 Hz,1H),6.48(d,J＝8.8 Hz,1H),6.20(d,J＝8.8 Hz,1H),3.09(s,3H),2.29(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:166.6,142.6,138.3,135.3,134.5,129.8,129.5,128.9,128.8(2×C),128.7,128.6,128.0(2×C),125.8,125.0,118.5,34.8,21.5.HRMS(ESI)m/z calculated for C 19 H 20 ON + [M+H] + 278.1539,found 278.1545.
2007:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.65(d,J＝15.6 Hz,1H),7.47-7.44(m,2H),7.36-7.32(m,3H),7.23(d,J＝8.0 Hz,2H),7.11(d,J＝8.0 Hz,2H),6.95(d,J＝15.6 Hz,1H),6.44(d,J＝8.8 Hz,1H),6.22(d,J＝8.8 Hz,1H),3.10(s,3H),2.31(s,3H). 13 C{ 1 H}NMR(100MHz,CDCl 3 )δ:166.5,142.6,138.2,135.2,131.5,129.7,129.4(2×C),128.8(2×C),128.6(2×C),128.1,128.0(2×C),125.5,118.3,24.6,21.3.HRMS(ESI)m/z calculated for C 19 H 20 ON + [M+H] + 278.1539,found 278.1548.
2008:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.57(d,J＝15.6 Hz,1H),7.48-7.45(m,2H),7.39-7.33(m,3H),7.30(d,J＝7.6 Hz,1H),7.20(dd,J＝13.2,6.4 Hz,1H),7.06(t,J＝7.6 Hz,1H),6.98(t,J＝9.2 Hz,1H),6.90(d,J＝15.6 Hz,1H),6.62(d,J＝8.8 Hz,1H),6.32(d,J＝8.8 Hz,1H),3.07(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:166.4,160.1(d,J＝248 Hz),142.9,135.1,130.9,129.9,129.8(d,J＝8.9 Hz),129.7,128.8(2×C),128.0(2×C),124.3(d,J＝3.0 Hz),122.6(d,J＝13.9 Hz),118.2,116.2(d,J＝3.7 Hz),115.7(d,J＝21.7 Hz),34.8. 19 F NMR(376 MHz,CDCl 3 )δ-114.9.HRMS(ESI)m/z calculated for C 18 H 17 ONF + [M+H] + 282.1289,found 282.1296.
2009:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.64(d,J＝15.6 Hz,1H),7.48-7.45(m,2H),7.36-7.33(m,3H),7.27(dd,J＝14.0,8.0 Hz,1H),7.10(d,J＝8.0 Hz,1H),7.00(d,J＝10.0Hz,1H),6.93(td,J＝8.0,2.4 Hz,1H),6.90(d,J＝15.6 Hz,1H),6.56(d,J＝8.8 Hz,1H),6.19(d,J＝8.8 Hz,1H),3.09(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:166.6,162.9(d,J＝245 Hz),143.2(2×C),136.7(d,J＝7.8 Hz),135.1,130.3(d,J＝8.3 Hz),130.0(d,J＝16 Hz),128.9(2×C),128.1(2×C),124.5(d,J＝2.3 Hz),123.4,118.1,115.4(d,J＝21.8 Hz),115.1(d,J＝21.1 Hz),34.9. 19 F NMR(376 MHz,CDCl 3 )δ-112.6.HRMS(ESI)m/z calculated for C 18 H 17 ONF + [M+H] + 282.1289,found 282.1297.
2010:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.63(d,J＝15.6 Hz,1H),7.46-7.43(m,2H),7.35-7.27(m,5H),6.98(t,J＝8.8 Hz,2H),6.91(d,J＝15.6 Hz,1H),6.47(d,J＝8.8 Hz,1H),6.20(d,J＝8.8 Hz,1H),3.08(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:166.5,162.2(d,J＝247Hz),142.9,135.1,130.6(d,J＝3.3 Hz),130.5(d,J＝8.0 Hz,2×C),129.9,128.8(2×C),128.7,128.0(2×C),124.1,118.2,115.8(d,J＝21.5 Hz,2×C),34.6. 19 F NMR(376 MHz,CDCl 3 )δ-112.5.HRMS(ESI)m/z calculated for C 18 H 17 ONF + [M+H] + 282.1289,found 282.1297.
2011:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.54(d,J＝15.6 Hz,1H),7.50-7.47(m,2H),7.38-7.34(m,3H),7.30-7.27(m,2H),7.21-7.12(m,2H),6.88(d,J＝15.6 Hz,1H),6.64(d,J＝8.8 Hz,1H),6.37(d,J＝8.8 Hz,1H),3.02(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:166.4,142.9,135.1,133.5,133.3,130.7,129.9,129.7,129.1,128.8(2×C),128.1(3×C),127.0,119.9,118.1,35.1.HRMS(ESI)m/z calculated for C 18 H 17 ONCl + [M+H] + 298.0993,found 298.0998.
2012:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.67(d,J＝15.6 Hz,1H),7.53-7.48(m,2H),7.42-7.36(m,3H),7.29(s,1H),7.25-7.21(m,3H),6.92(d,J＝15.6 Hz,1H),6.59(d,J＝8.8Hz,1H),6.17(d,J＝8.8 Hz,1H),3.10(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:166.5,143.1,136.4,135.0,134.5,130.2,129.9(2×C),128.8(2×C),128.7(2×C),128.0(2×C),126.6,122.7,118.0,34.9.HRMS(ESI)m/z calculated for C 18 H 17 ClNO + [M+H] + 298.0993,found 298.1000.
2013:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.66(d,J＝15.6 Hz,1H),7.49-7.46(m,2H),7.38-7.35(m,3H),7.28(ABq,J＝8.8 Hz,4H),6.92(d,J＝15.6 Hz,1H),6.55(d,J＝8.8 Hz,1H),6.21(d,J＝8.8 Hz,1H),3.10(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:166.5,143.1,135.1,133.8,133.0,130.0(2×C),129.9,129.5,129.0(2×C),128.8(2×C),128.1(2×C),123.7,118.1,34.8.HRMS(ESI)m/z calculated for C 18 H 17 ONCl + [M+H] + 298.0993,found 298.0999.
2014:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.58(d,J＝7.2 Hz,1H),7.57(d,J＝15.6Hz,1H),7.50-7.45(m,3H),7.39-7.29(m,5H),6.88(d,J＝15.6 Hz,1H),6.69(d,J＝8.8 Hz,1H),6.43(d,J＝8.8 Hz,1H),2.96(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:166.6,143.3,134.9,133.6,132.0,131.1,130.3,130.0,128.8(2×C),128.1(2×C),128.0(q,J＝29.6 Hz),127.8,126.1(q,J＝5.4 Hz),124.2(q,J＝272 Hz)118.5,117.9,35.1. 19 F NMR(376 MHz,CDCl 3 )δ-60.7.HRMS(ESI)m/z calculated for C 19 H 17 ONF 3 + [M+H] + 332.1257,found 332.1265.
2015:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.62(d,J＝15.6 Hz,1H),7.53-7.49(m,2H),7.48-7.40(m,4H),7.35-7.32(m,3H),6.88(d,J＝15.6 Hz,1H),6.61(d,J＝8.8 Hz,1H),6.22(d,J＝8.8 Hz,1H),3.07(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:166.5,143.2,135.5,135.0,131.5,131.1(q,J＝32.1 Hz),130.6,130.0,129.2,128.8(2×C),128.0(2×C),125.6(q,J＝3.7 Hz),124.6,123.9(q,J＝271 Hz),122.4,118.0,34.9. 19 F NMR(376 MHz,CDCl 3 )δ-62.9.HRMS(ESI)m/z calculated for C 19 H 17 ONF 3 + [M+H] + 332.1257,found 332.1263.
2016:Yellowish oil. 1 H NMR(400MHz,CDCl 3 )δ:7.61(d,J＝15.6Hz,1H),7.54(d,J＝8.0Hz,2H),7.47-7.43(m,2H),7.39(d,J＝8.0Hz,2H),7.37-7.33(m,3H),6.88(d,J＝15.6Hz,1H),6.63(d,J＝8.8Hz,1H),6.23(d,J＝8.8Hz,1H),3.08(s,3H). 13 C{ 1 H}NMR(100MHz,CDCl 3 )δ:166.5,143.3,138.3,135.0,131.0,130.0,129.8(q,J＝33Hz),128.9(2×C),128.8(2×C),128.0(2×C),125.6(q,J＝3.3Hz,2×C),124.0(q,J＝265Hz),122.7,118.0,35.0. 19 F NMR(376MHz,CDCl 3 )δ-62.7；HRMS(ESI)m/z calculated for C 19 H 17 ONF 3 + [M+H] + 332.1257,found 332.1265.
2017:Yellowish oil. 1 H NMR(400MHz,CDCl 3 )δ:8.00(dd,J＝8.0Hz,1H),7.82(d,J＝8.0Hz,1H),7.76(t,J＝4.4Hz,1H),7.58(d,J＝15.6Hz,1H),7.55-7.46(m,3H),7.45-7.41(m,2H),7.38-7.35(m,2H),7.34-7.30(m,2H),6.95(d,J＝15.6Hz,1H),6.86(d,J＝8.8Hz,1H),6.67(d,J＝8.8Hz,1H),2.90(s,3H). 13 C{ 1 H}NMR(100MHz,CDCl 3 )δ:166.6,142.9,135.1,133.7,132.1,131.4,130.7,129.8,128.8(2×C),128.4,128.0(2×C),126.7,126.5,126.1(2×C),125.6,124.2,119.4,118.3,34.9.HRMS(ESI)m/z calculated for C 22 H 20 ON + [M+H] + 314.1539,found 314.1544.
2018:Yellowish oil. 1 H NMR(400MHz,CDCl 3 )δ:7.80-7.75(m,4H),7.66(d,J＝15.6Hz,1H),7.49-7.43(m,5H),7.33-7.31(m,3H),7.00(d,J＝15.6Hz,1H),6.60(d,J＝8.8Hz,1H),6.39(d,J＝8.8Hz,1H),3.13(s,3H). 13 C{ 1 H}NMR(100MHz,CDCl 3 )δ:166.8,143.0,135.2,133.3,132.9,132.1,129.8,129.2,128.8(2×C),128.5,128.4,128.2,128.0(2×C),127.7,126.6,126.5,126.1,124.7,118.4,35.0.HRMS(ESI)m/z calculated for C 22 H 20 ON + [M+H] + 314.1539,found314.1546.
Synthesis of Compounds 2021-2046 from example 2.
Synthesis of compound a:
100ml two-neck flask, air suction head and magneton oven are dried, take out and assemble and vacuumize to room temperature and exchange argon, weigh o-methoxybenzaldehyde (1.36 g,10 mmol) in sample bottle, suck anhydrous THF (40 ml) and put into flask, weigh ethoxyformylmethylene triphenylphosphine (4.176 g,12 mmol), add flask slowly under ice bath condition, remove ice bath after ice bath reaction for 10min, quench reaction after reaction overnight, add saturated ammonium chloride solution (20 ml) under ice bath condition, evaporate under reduced pressure to remove THF, add ethyl acetate (20 ml) to extract, wash saturated sodium chloride solution (20 ml) 1 time, dry organic phase with anhydrous sodium sulfate for 30min, evaporate under reduced pressure to remove solvent, column chromatography purification, eluent is petroleum ether and ethyl acetate (v: v=20:1), get colorless oily liquid A (2.02 g,9.8 mmol), yield: 98%.
Synthesis of Compound B:
10ml of the tube was capped, A (206 mg,1 mmol) was weighed, ammonia-methanol solution (2 ml) was added, the plug was screwed, the reaction was performed at room temperature for 3 days, the solvent was removed by evaporation under reduced pressure to give crude product, which was purified by column chromatography with petroleum ether and acetone (v: v=5:1) to give B (124 mg,0.70 mol) as a white solid in 76% yield.
Synthesis of Compound C:
taking 100mL of a tube for sealing, adding a magneton, weighing iodine (2.80 g,11.0 mmol), pouring argon (lasting for 1 min), reversely buckling a rubber plug, inserting a coarse needle, sucking anhydrous benzene (12 mL), pouring into the tube for sealing, adding anhydrous morpholine (2.62 mL,30.0 mmol), and reacting for 30min at room temperature. Phenylacetylene (2.25 g,10.0 mmol) was weighed into a sample bottle, diluted with anhydrous benzene (10 mL) and slowly dropped into a vial, and the vial was washed twice with anhydrous benzene (8 mL) and then was filled into a vial. The reaction mixture was heated to 45℃in an oil bath for 24 hours, cooled to room temperature, filtered through celite, and washed with ethyl acetate (3X 20 mL). The filtrate was collected, washed 1 time with saturated ammonium chloride solution (20 ml) and saturated sodium chloride solution (20 ml) in this order, the organic phase was collected, dried over anhydrous sodium sulfate for 30min, the solvent was removed by rotary evaporation, and purified by column chromatography, eluting with petroleum ether, to give yellow oily liquid C (2.23 g,9.8 mmol), yield: 98%.
Synthesis of Compound D:
a100 mL tube was capped, C (2.23 g,9.8 mmol) was weighed into the tube cap, magneton, THF (20 mL) and water (20 mL) were added, 4-methylbenzenesulfonyl hydrazine (3.65 g,19.6 mmol) and anhydrous sodium acetate (2.41 g,29.4 mmol) were weighed into the tube cap, the tube cap was screwed down, the oil bath at 120℃was performed for 12h, then the tube cap was naturally cooled to room temperature, saturated ammonium chloride solution was added under ice bath to quench the reaction, ethyl acetate (3X 20 mL) was extracted, saturated sodium chloride solution (20 mL) was washed 1 time, the organic phase anhydrous sodium sulfate was dried for 30min, the solvent was removed by rotary evaporation, column chromatography was performed, and the eluent was petroleum ether to give colorless oily liquid D (1.31 g,5.68 mmol), yield: 58%.
Synthesis of compound E:
10ml Schlenk tube and magneton are taken, dried, vacuum pumped to room temperature after assembly (rubber plug is plugged), argon is introduced, B (195 mg,1.1 mmol) is added, cuI (9.5 mg,0.05 mmol) and Cs are weighed in 2 CO 3 (407 mg,1.25 mmol), D (230 mg,1 mmol) was weighed, anhydrous THF (5 mL) was aspirated, D1 was diluted by 2.5mL, and 2.5mL was pipetted into the sample bottle in two washes. Then, DMEDA (10.8. Mu.L, 0.1 mmol) was added dropwise thereto, the rubber stopper was replaced with a glass stopper coated with a small amount of grease, the Schlenk tube was sealed, and the reaction was carried out in an oil bath at 65 ℃. After 3h of reaction, the oil bath is removed, and the reaction is naturally restored to room temperature. The solid was filtered off through celite and washed with ethyl acetate (30 ml). The solvent was removed by rotary evaporation. Column chromatography purification, eluting with petroleum ether and ethyl acetate (v/v=5:1), gave after purification a pale yellow solid E (209 mg,0.75 mmol), yield: 75%.
Synthesis of compound S:
a25 mL two-neck flask, a magnet and an air suction head are taken for drying, an assembling device is vacuumized to room temperature, argon is introduced, E (0.75 mmol) is weighed, anhydrous DMF (3 mL) is sucked, and NaH (4.5 mmol) with the purity of 60% is added under the ice bath condition. After the ice bath reaction was continued for 30 minutes, methyl iodide (5.25 mmol) was slowly added dropwise. And (3) reacting for 3 hours at room temperature, and slowly dripping water to quench the reaction under the ice bath condition. Ethyl acetate (3 x 10 ml) was extracted, the organic phases were combined, washed 1 time with saturated sodium chloride solution, dried over anhydrous sodium sulfate for 30min, and the solvent was removed by rotary evaporation. Purifying by column chromatography, eluting with petroleum ether and ethyl acetate (v/v=10:1) to obtain the target compound S.
2021:Yellowish oil. 1 H NMR(400MHz,CDCl 3 )δ:7.59(d,J＝15.6Hz,1H),7.33-7.27(m,4H),7.25-7.20(m,2H),7.05(d,J＝7.6Hz,1H),6.96(s,1H),6.91(d,J＝15.6Hz,1H),6.88(dd,J＝7.6,2.0Hz,1H),6.49(d,J＝8.8Hz,1H),6.24(d,J＝8.8Hz,1H),3.81(s,3H),3.09(s,3H). 13 C{ 1 H}NMR(100MHz,CDCl 3 )δ:166.4,159.8,142.6,136.6,134.5,129.8,128.9,128.7(4×C),128.2,125.2,120.6,118.7,115.4,113.2,55.4,34.7.HRMS(ESI)m/z calculated for C 19 H 20 O 2 N + [M+H] + 294.1489,found 294.1492.
2023:Yellowish oil. 1 H NMR(400MHz,CDCl 3 )δ:7.90(d,J＝15.6Hz,1H),7.40(d,J＝7.6Hz,1H),7.34-7.28(m,4H),7.26-7.20(m,2H),7.17-7.13(m,2H),6.84(d,J＝15.6Hz,1H),6.49(d,J＝8.8Hz,1H),6.23(d,J＝8.8Hz,1H),3.10(s,3H),2.38(s,3H). 13 C{ 1 H}NMR(100MHz,CDCl 3 )δ:166.6,140.6,137.7,134.5,134.3,130.7,129.5,128.9,128.7(4×C),128.2,126.3,126.2,125.2,119.6,34.7,19.9.HRMS(ESI)m/z calculated for C 19 H 20 ON + [M+H] + 278.1539,found278.1542.
2024:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.64(d,J＝15.6 Hz,1H),7.37-7.31(m,4H),7.30-7.23(m,4H),7.17(d,J＝7.2 Hz,1H),6.94(d,J＝15.6 Hz,1H),6.54(d,J＝8.8 Hz,1H),6.27(d,J＝8.8 Hz,1H),3.11(s,3H),2.37(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:166.7,143.1,138.5,135.2,134.6,130.7,129.0,128.9(2×C),128.8(2×C),128.7,128.6,128.2,125.3,125.0,118.1,34.8,21.5.HRMS(ESI)m/z calculated for C 19 H 20 ON + [M+H] + 278.1539,found278.1542.
2027:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.55(d,J＝15.6 Hz,1H),7.32-7.27(m,5H),7.24-7.22(m,1H),7.19(d,J＝8.0 Hz,1H),7.11(d,J＝10.0 Hz,1H),7.01(td,J＝8.0,2.0 Hz,1H),6.91(d,J＝15.6 Hz,1H),6.46(d,J＝8.8 Hz,1H),6.27(d,J＝8.8 Hz,1H),3.10(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:166.0,163.0(d,J＝245 Hz),141.2(d,J＝2.6 Hz),137.5(d,J＝7.7 Hz),134.3,130.3(d,J＝8.2 Hz),128.8(2×C),128.7(3×C),128.2,125.6,124.1(d,J＝2.7Hz),119.7,116.6(d,J＝21.3 Hz),114.0(d,J＝21.6 Hz),34.7. 19 F NMR(376 MHz,CDCl 3 )δ:-113.0.HRMS(ESI)m/z calculated for C 18 H 17 ONF + [M+H] + 282.1289,found 282.1292.
2028:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.57(d,J＝15.6 Hz,1H),7.42(dd,J＝8.8,5.6 Hz,2H),7.32-7.27(m,4H),7.25-7.20(m,1H),7.02(t,J＝8.8 Hz,2H),6.84(d,J＝15.6Hz,1H),6.48(d,J＝8.8 Hz,1H),6.25(d,J＝8.8 Hz,1H),3.09(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:166.4,163.6(d,J＝249 Hz),141.5,134.5,131.5(d,J＝3.3 Hz),129.8(d,J＝8.3 Hz,2×C),128.9(d,J＝7.6 Hz,2×C),128.8(2×C),128.7(2×C),128.2,125.3,118.1(d,J＝1.9 Hz),115.9(d,J＝21.6 Hz),34.8. 19 F NMR(376 MHz,CDCl 3 )δ:-110.6.HRMS(ESI)m/z calculated for C 18 H 17 ONF + [M+H] + 282.1289,found 282.1292.
2033:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.64(s,1H),7.60(d,J＝15.6 Hz,1H),7.58-7.56(m,2H),7.45(t,J＝7.6 Hz,1H),7.34-7.28(m,4H),7.25-7.20(m,1H),6.98(d,J＝15.6Hz,1H),6.48(d,J＝8.8 Hz,1H),6.31(d,J＝8.8 Hz,1H),3.14(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:165.7,140.7,136.0,134.3,131.2,131.1(q,J＝32.2 Hz),129.3,128.8(2×C),128.6(3×C),128.2,126.0(q,J＝3.5 Hz),125.7,124.2(q,J＝3.6 Hz),123.9(q,J＝271 Hz),120.3,34.7. 19 F NMR(376 MHz,CDCl 3 )δ:-62.8.HRMS(ESI)m/z calculated for C 19 H 17 ONF 3 + [M+H] + 332.1257,found 332.1260.
2036:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.86-7.77(m,5H),7.59(dd,J＝8.4,1.2Hz,1H),7.52-7.46(m,2H),7.36-7.29(m,4H),7.25-7.20(m,1H),7.05(d,J＝15.6 Hz,1H),6.55(d,J＝8.8 Hz,1H),6.28(d,J＝8.8 Hz,1H),3.12(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:166.6,142.8,134.5,134.1,133.4,132.7,129.7,129.0,128.8(4×C),128.6,128.5,128.2,127.8,127.0,126.7,125.1,123.8,118.5,34.8.HRMS(ESI)m/z calculated for C 22 H 20 ON + [M+H] + 314.1539,found 314.1543.
2037:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.96(d,J＝15.6 Hz,1H),7.42(d,J＝7.6Hz,1H),7.25-7.28(m,5H),7.25-7.21(m,1H),7.03(d,J＝15.6 Hz,1H),6.91(t,J＝7.6 Hz,1H),6.88(d,J＝7.6 Hz,1H),6.52(d,J＝8.8 Hz,1H),6.20(d,J＝8.8 Hz,1H),3.84(s,3H),3.07(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:167.1,158.3,138.3,134.7,131.0,129.2,128.9,128.8(2×C),128.7(2×C),128.0,124.3,124.2,120.6,119.0,111.1,55.5,34.7.HRMS(ESI)m/z calculated for C 19 H 20 O 2 N + [M+H] + 294.1489,found 294.1492.
2038:Yellowish oil. 1 H NMR(400 MHz,CD 3 OD)δ:7.41(d,J＝15.6 Hz,1H),7.39(d,J＝8.8 Hz,2H),7.29-7.27(m,4H),7.22-7.17(m,1H),6.88(d,J＝8.8 Hz,2H),6.85(d,J＝15.6 Hz,1H),6.52(d,J＝8.8 Hz,1H),6.38(d,J＝8.8 Hz,1H),3.8(s,3H),3.06(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:168.7,162.7,143.6,135.9,130.6(2×C),129.8,129.7(2×C),129.6(2×C),129.1,128.8,127.3,116.6,115.2(2×C),55.8,35.0.HRMS(ESI)m/z calculated for C 19 H 20 O 2 N + [M+H] + 294.1489,found,294.1492.
2039:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.63(d,J＝15.6 Hz,1H),7.36(d,J＝8.0Hz,2H),7.34-7.28(m,4H),7.25-7.20(m,1H),7.15(d,J＝8.0 Hz,2H),6.90(d,J＝15.6 Hz,1H),6.51(d,J＝8.8 Hz,1H),6.23(d,J＝8.8 Hz,1H),3.08(s,3H),2.35(s,3H). 13 C{ 1 H}NMR(100MHz,CDCl 3 )δ:166.7,142.8,140.1,134.5,132.5,129.5(2×C),129.0,128.8(2×C),128.7(2×C),128.1,128.0(2×C),124.9,117.2,34.7,21.5.HRMS(ESI)m/z calculated for C 19 H 20 ON + [M+H] + 278.1539,found 278.1542.
2040:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.70(d,J＝15.6 Hz,1H),7.42(td,J＝7.6,1.6 Hz,1H),7.32-7.27(m,5H),7.25-7.20(m,1H),7.10(t,J＝7.6 Hz,1H),7.06(dd,J＝7.6,1.6Hz,1H),7.04(d,J＝15.6 Hz,1H),6.48(d,J＝8.8 Hz,1H),6.25(d,J＝8.8 Hz,1H),3.10(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:166.4,161.4(d,J＝252 Hz),135.6,134.5,131.1(d,J＝8.6Hz),129.6(d,J＝3.2 Hz),128.8,128.7(4×C),128.2,125.3,124.3(d,J＝3.5 Hz),123.3(d,J＝11.6 Hz),121.2(d,J＝7.3 Hz),116.2(d,J＝21.8 Hz),34.8. 19 F NMR(376 MHz,CDCl 3 )δ:-114.1.HRMS(ESI)m/z calculated for C 18 H 17 ONF + [M+H] + 282.1289,found 282.1292.
2041:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.98(d,J＝15.6 Hz,1H),7.43(dd,J＝7.6,2.0 Hz,1H),7.36(dd,J＝7.6,1.6 Hz,1H),7.33-7.30(m,4H),7.26-7.18(m,3H),6.91(d,J＝15.6Hz,1H),6.47(d,J＝8.8 Hz,1H),6.24(d,J＝8.8 Hz,1H),3.10(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:166.0,138.7,134.9,134.4,133.6,130.5,130.1,128.8(3×C),128.7(2×C),128.2,127.7,126.9,125.4,121.2,34.8.HRMS(ESI)m/z calculated for C 18 H 17 ONCl + [M+H] + 298.0993,found298.0996.
2042:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.52(d,J＝15.6 Hz,1H),7.39(s,1H),7.32-7.20(m,8H),6.91(d,J＝15.6 Hz,1H),6.47(d,J＝8.8 Hz,1H),6.27(d,J＝8.8 Hz,1H),3.10(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:166.0,141.1,137.1,134.7,134.3,130.0,129.6,128.8(2×C),128.7(3×C),128.3,127.5,126.4,125.7,119.8,34.8.HRMS(ESI)m/z calculated for C 18 H 17 ONCl + [M+H] + 298.0993,found 298.0996.
2043:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.54(d,J＝15.6 Hz,1H),7.36(d,J＝8.4Hz,2H),7.32-7.27(m,6H),7.24-7.20(m,1H),6.89(d,J＝15.6 Hz,1H),6.47(d,J＝8.8 Hz,1H),6.25(d,J＝8.8 Hz,1H),3.09(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:166.2,141.3,135.6,134.4,133.7,129.2(2×C),129.1(2×C),128.9(2×C),128.8,128.7(2×C),128.3,125.5,118.9,34.8.HRMS(ESI)m/z calculated for C 18 H 17 ONCl + [M+H] + 298.0993,found 298.0996.
2044:Yellowish oil. 1 H NMR(400 MHz,CDCl 3 )δ:7.97(dq,J＝15.6,2.0 Hz,1H),7.65(d,J＝7.6 Hz,1H),7.50-7.37(m,3H),7.36-7.29(m,4H),7.27-7.21(m,1H),6.86(d,J＝15.6 Hz,1H),6.45(d,J＝8.8 Hz,1H),6.25(d,J＝8.8 Hz,1H),3.11(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl 3 )δ:165.6,138.4,134.5,134.3,131.9,130.1,129.1,128.8(2×C),128.7(2×C),128.6,128.4,128.0,126.1(q,J＝5.6Hz),125.6,124.0(q,J＝272Hz),122.9,34.8. 19 F NMR(376MHz,CDCl 3 )δ:-62.8.HRMS(ESI)m/z calculated for C 19 H 17 ONF 3 + [M+H] + 332.1257,found 332.1260.
2045:Yellowish oil. 1 H NMR(400MHz,CDCl 3 )δ:7.48(d,J＝15.6Hz,1H),7.44(ABq,J＝8.4Hz,4H),7.21-7.18(m,4H),7.15-7.10(m,1H),6.88(d,J＝15.6Hz,1H),6.36(d,J＝8.8Hz,1H),6.19(d,J＝8.8Hz,1H),3.02(s,3H). 13 C{ 1 H}NMR(100MHz,CDCl 3 )δ:165.8,140.8,138.7,134.3,131.2(q,J＝32.3Hz),128.9(2×C),128.7(2×C),128.6,128.3,128.1(2×C),125.9,125.8(q,J＝3.7Hz,2×C),124.0(q,J＝270Hz),121.0,34.8. 19 F NMR:(376MHz,CDCl 3 )δ-62.7.HRMS(ESI)m/z calculated for C 19 H 17 ONF 3 + [M+H] + 332.1257,found 332.1260.
2046:Yellowish oil. 1 H NMR(400MHz,CDCl 3 )δ:8.46(d,J＝15.2Hz,1H),8.15(d,J＝7.6Hz,1H),7.93-7.85(m,2H),7.59-7.51(m,3H),7.45(t,J＝7.6Hz,1H),7.39-7.32(m,4H),7.28-7.24(m,1H),7.02(d,J＝15.2Hz,1H),6.53(d,J＝8.8Hz,1H),6.28(d,J＝8.8Hz,1H),3.18(s,3H). 13 C{ 1 H}NMR(100MHz,CDCl 3 )δ:166.4,140.0,134.5,133.7,132.9,131.6,130.0,128.9,128.8(2×C),128.7(2×C),128.6,128.4,126.7,126.2,125.5,125.4,124.8,123.9,121.3,34.8.HRMS(ESI)m/z calculated for C 22 H 20 ON + [M+H] + 314.1539,found 314.1543.
Example 2 bacteriostasis experiment
Antibacterial tests are carried out on the cis-enamide derivatives.
Preparation of Potato Medium (PDA)
25g of potato dextrose water, 20g of agar and 1000ml of distilled water. Weighing potato dextrose 25g, weighing agar 20g, heating and dissolving in 1000ml double distilled water, subpackaging in conical flasks, sterilizing at 121deg.C for more than 15 min under high pressure, and placing in dark place for use.
Preservation and culture of pathogenic fungi
Heating sterilized PDA culture medium into flowing state with microwave oven, pouring 15ml culture medium into sterile culture dish with diameter of 9cm on ultra-clean workbench, solidifying, inoculating 0.5cm fungus cake, sealing, culturing at 28deg.C, storing in refrigerator at 5deg.C, and activating once every two months.
Bacteriostasis experiment
Taking sclerotinia as an example:
a) The sclerotinia sclerotiorum stored in a refrigerator at 5 ℃ is transferred to a biochemical incubator at 28 ℃ for standby after 24 hours in advance.
b) Under aseptic condition, dissolving the test medicine with DMSO, sterilizing by suction filtration, and preparing into mother liquor with concentration of 5.00
mg/mL。
c) The mother solutions of 0.3ml, 0.15ml and 0ml were aspirated into 2ml centrifuge tubes with a manual pipette, and DMSO was added to 0.3ml and water was added to 1ml. Pouring into 49mL PDA culture medium (the culture medium is cooled to 55 ℃ in advance), shaking up the culture medium and pouring into a culture dish (sterilized in advance) while the culture medium and the PDA culture medium are hot, wherein each dish is 10mL, cooling is carried out for standby, the final compound concentration in the culture medium is 50 mug/mL, 25 mug/mL, 0 mug/mL, and the final DMSO content is 1%.
d) Preparing a pre-activated purified test strain, preparing a bacterial cake by using a puncher with the diameter of 5mm, and selecting the edge of a culture dish at the punching position. The mycelium-containing pellet was transferred face down to the top of the prepared medicated medium with an inoculating loop, and 1 pellet was placed in each dish. 3 groups of the culture medium are repeatedly prepared for each concentration, and the culture medium is cultivated in a constant temperature incubator at 28 ℃ after marking is performed, and the culture medium is stored in an inverted manner.
e) After 24h of culture (different fungi, different growth rates of hyphae and different observation times, the diameter of a blank treatment group bacterial cake is selected to be 70-80% of that of a culture dish to observe the condition of a liquid medicine treatment group), the colony diameter is measured by a crisscross method, and the growth inhibition rate of the hyphae is recorded and calculated by adopting the following test:
colony expansion diameter (mm) =colony diameter average-5 (cake diameter, mm)
Hypha growth inhibition (%) = (control colony expansion diameter-treatment colony expansion diameter)/control colony expansion diameter x 100%
f) And 5 groups of concentration gradients are set according to the observation result, the steps c-e are repeated, and the corresponding bacteriostasis rate is calculated.
g) Data were treated with Excel 2004 to calculate the rate of inhibition and standard deviation of the rate of inhibition, fit the virulence regression equation, and use Spss
24 software, by "P" analysis, calculates the median effective concentration (51%effective concentration,EC 50 ) 95% confidence interval. And the following test was used to calculate the relative virulence coefficients of the different compounds for Lansiumamide B:
relative virulence coefficient = lansium amide B EC against fungi 50 EC of target Compounds against fungi 50
Inhibitory Activity of Compounds against 3 pathogenic fungi
(1) Preliminary evaluation of Lansiumamide B and its derivatives for inhibiting Activity against 3 pathogenic fungi
The inhibition rates of 34 compounds synthesized at a concentration of 50. Mu.g/mL and 25. Mu.g/mL on Sclerotinia sclerotiorum, rhizoctonia solani and Botrytis cinerea were determined using commercially available carbendazim as a positive control. As can be seen from Table 1, lansium amide B and its derivatives have a large difference between the inhibition rate of three pathogenic fungi, which is not 99% at 50. Mu.g/mL of the drug solution concentration, and the flexible force of the bacteria. The inhibition rate of the Lansium amide B and the derivatives thereof to the sclerotinia is in the range of 58.03-97.83% under the concentration of 50 mug/mL of the liquid medicine, and the inhibition rate of the sclerotinia is more than 34% under the concentration of 25 mug/mL of the liquid medicine except 2004; the inhibition rate of Lansium mide B and the derivatives thereof to rice sheath blight is 56.72-95.44% under the concentration of 50 mug/mL liquid medicine, and the inhibition rate of the Lansium B and the derivatives thereof to sclerotinia is more than 38% under the concentration of 25 mug/mL liquid medicine except 2017; lansium amide B and its derivatives have no obvious antibacterial effect on the gray mold, and the highest inhibition rate is 2009 and only reaches 51.3% at the concentration of 50 mug/mL of the liquid medicine.
Table 1 inhibition of 3 pathogenic fungi by derivatives (%)
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(2) Inhibitory Activity of partial Lansiumamide B derivatives against 2 pathogenic fungi
6 compounds with obviously better effect than Lansium amide B on inhibiting sclerotinia at the initial screening concentration are selected for toxicity measurement, and the commercial carbendazim is used as a positive control. As shown in Table 2, 2008, 2011, 2028 and 2037 have significantly improved inhibiting activity on sclerotinia as compared with Lansiumamide B, and the relative toxicity is 2.00 to/10.78 times, wherein 2037 has the best inhibiting effect as compared with Lansiumamide B, and EC thereof is 10.78 times 50 Only 1.51. Mu.g/mL. 2002. 2005 EC against sclerotinia 50 No difference from lansium B was significant.
Table 3-5 inhibitory Effect of derivatives on Sclerotinia sclerotiorum
And 6 compounds are selected, the rice sheath blight inhibition effect is obviously better than that of Lansiumamide B compounds under the primary screening concentration, and the commercial carbendazim is used as a positive control medicament. As shown in Table 3, 2028 has significantly improved Rhizoctonia solani inhibitory activity compared with Lansium amide B, and has a relative virulence of 2.49 times, and EC 50 Only 2.04. Mu.g/mL. 2002. 2005, 2008, 2011 and 2040 have no obvious difference in bacteriostasis effect on rice sheath blight compared with Lansiumamide B.
Table 3 inhibition of Rhizoctonia solani by derivatives
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Claims (7)

1. Application of cis-enamide derivatives or salts thereof in preparation of antibacterial drugs;
the chemical structure of the cis-enamide derivative is shown as any one of (a),
(a) Wherein R is 1 Is hydrogen, methoxy, methyl, trifluoromethyl, benzo fused ring or halogen;
R 2 is methyl, methoxy, trifluoromethyl, benzofused ring or halogen.
2. The use according to claim 1, wherein said cis enamide derivative is one of the following compounds:
3. the use according to claim 2, wherein the cis enamide derivative has the structural formula shown in any one of the following:
4. the use according to claim 1, characterized in that the cis-enamide derivative or its salt is used for preparing bacteriostatic pesticides.
5. The use according to claim 1 or 4, characterized in that the cis-enamide derivative or its salt is used for preparing anti-sclerotinia drugs.
6. The use according to claim 1 or 4, characterized in that the cis enamide derivative or its salt is used for preparing the anti-rice sheath blight drug.
7. The use according to claim 1 or 4, characterized in that the cis-enamide derivatives or salts thereof are used for the preparation of antimycotic drugs.
CN202310481215.9A 2023-04-28 2023-04-28 Application of cis-enamide derivative in preparation of antibacterial drugs Pending CN116530514A (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104247708A (en) * 2013-06-26 2014-12-31 中国中化股份有限公司 Application of lansenamide B in preparation of pesticides
CN107318839A (en) * 2016-04-28 2017-11-07 闫合 A kind of bactericide and its application
CN113796380A (en) * 2021-10-11 2021-12-17 江西农业大学 Application of clausena lansium alkaloid and salt thereof in preparation of products for inhibiting phytophthora and/or ring rot activity

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104247708A (en) * 2013-06-26 2014-12-31 中国中化股份有限公司 Application of lansenamide B in preparation of pesticides
CN107318839A (en) * 2016-04-28 2017-11-07 闫合 A kind of bactericide and its application
CN113796380A (en) * 2021-10-11 2021-12-17 江西农业大学 Application of clausena lansium alkaloid and salt thereof in preparation of products for inhibiting phytophthora and/or ring rot activity

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Title
AL-MASUM, MOHAMMAD: "Cu-Pd dual catalyst system for amide styrylation reaction from potassium styryltrifluoroborates and amides", INTERNATIONAL JOURNAL OF ORGANIC CHEMISTRY, vol. 7, no. 3, 31 December 2017 (2017-12-31), pages 254 - 262 *
LI, LICHUN: "Antibacterial activity of Lansiumamide B to tobacco bacterial wilt (Ralstonia solanacearum)", MICROBIOLOGICAL RESEARCH, 31 December 2014 (2014-12-31), pages 522 - 526 *
XU, HUIYOU 等: "Synthesis and fungicidal activity of lansiumamide A and B and their derivatives", MOLECULES, vol. 23, no. 7, 31 December 2018 (2018-12-31), pages 1 - 8 *
刘艳霞;巩自勇;万树青;: "黄皮酰胺类生物碱的提取及对7种水果病原真菌的抑菌活性", 植物保护, no. 05, 8 October 2009 (2009-10-08) *

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