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CN116235856A - Application of crocin-1 and crocin-2 - Google Patents

Application of crocin-1 and crocin-2 Download PDF

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Publication number
CN116235856A
CN116235856A CN202310024976.1A CN202310024976A CN116235856A CN 116235856 A CN116235856 A CN 116235856A CN 202310024976 A CN202310024976 A CN 202310024976A CN 116235856 A CN116235856 A CN 116235856A
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China
Prior art keywords
nmr
saffron
glycoside
cdcl
crocin
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CN202310024976.1A
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Chinese (zh)
Inventor
李玲
邹吉勇
游胜勇
邓朝阳
徐长江
陈桂华
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Institute of Applied Chemistry Jiangxi Academy of Sciences
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Institute of Applied Chemistry Jiangxi 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
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/14—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings
    • A01N43/16—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings with oxygen as the ring hetero atom
    • 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
    • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
    • 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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  • Life Sciences & Earth Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Environmental Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Chemical & Material Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Health & Medical Sciences (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Saccharide Compounds (AREA)

Abstract

The invention belongs to the technical field of pesticides, and provides application of saffron glycoside-1 and saffron glycoside-2, wherein natural products of saffron glycoside-1 and saffron glycoside-2 are used as active lead compounds, and a pesticide for resisting tobacco mosaic virus is synthesized through a structure-activity relationship or is directly used for resisting the tobacco mosaic virus, so that the pesticide is used for preventing and treating the tobacco mosaic virus.

Description

Application of crocin-1 and crocin-2
Technical Field
The invention relates to application of crocin-1 and crocin-2, and belongs to the technical field of pesticides.
Background
With the increasing population of the world and the changing dietary structure of people, the pressure of grain production is increasing. And diseases, insects and grasses bring great threat to the production of grains, and continuous and effective control is required. Meanwhile, the environmental, toxicological and management requirements of the application of the agrochemical products are continuously strict, and the requirements on pest control products are also continuously increased. And the sustained development of disease and pest control agent resistance further limits the application of the medicine. Therefore, there is a continuous need to discover and develop new, effective, economical pest control agents to increase crop yield and to supply an increasing number of humans.
Natural products are primary or secondary metabolites produced by living cells. Historically, natural products have been an important component of medicine and a major tool in agriculture for the control of weeds, pathogens and pests. Most natural products are unstable in the environment or have toxicity, insecticidal spectrum, light stability or production problems, especially in today's strict regulatory environments, which need to be solved by structural modification prior to commercialization. The synthesis of natural product derivatives also provides tools for the study of chemical biology, and can determine the relationship between structure and biological activity, and understand the action mode of natural products and biological targets.
Crocin-1 and crocin-2 are diester derivatives of crocetin and sugar, exist in traditional Chinese medicines of gardenia and saffron, have the effects of resisting apoptosis, hyperlipidemia, atherosclerosis and oxidization, and can also grow various cancer cells. In the agricultural biological activity research process of gardenia yellow in gardenia, the crocin-1 and crocin-2 have good tobacco mosaic virus resistance activity.
Disclosure of Invention
The invention aims to provide a preparation method of saffron glycoside-1 and saffron glycoside-2 and an application thereof in plant protection.
The invention provides application of saffron glycoside-1 and saffron glycoside-2, wherein natural products of saffron glycoside-1 and saffron glycoside-2 are used as active lead compounds, and pesticides for resisting tobacco mosaic virus are synthesized through a structure-activity relationship.
The invention provides application of crocin-1 and crocin-2, which are directly used for resisting tobacco mosaic virus and preventing and treating tobacco mosaic virus.
The invention discovers that the natural products saffron glycoside-1 and saffron glycoside-2 show higher anti-plant virus activity level than commercial variety ribavirin for the first time, and can be used as novel plant source pesticides or can be developed as lead compounds.
Detailed Description
The present invention will be described in further detail with reference to examples, but the present invention is not limited to these examples.
Example 1
Preparation and structural characterization of saffron glycoside-1 and saffron glycoside-2:
150g of cape jasmine fruit powder is soaked in 1200ml of methanol for 72 hours, and the solution is continuously stirred during the soaking. Suction filtering, and spin drying the filtrate to obtain 33.7g of fructus Gardeniae crude extract. Separating the crude extract with macroporous adsorbent resin, eluting with water and ethanol to obtain five components (1-5). The component 4 was separated by silica gel column chromatography to obtain six components (4.1-4.6). And recrystallizing the component 4.6 to obtain the crocin-1. The component 4.5 is further separated by preparative chromatography to obtain the crocin-2.
Compound 1: saffron glycoside-1: mp 229-231 ℃; 1 H NMR(400MHz,DMSO)δ7.36(d,J＝10.8Hz,2H),6.90–6.79(m,4H),6.72–6.63(m,2H),6.54(d,J＝10.2Hz,2H),5.42(d,J＝7.6Hz,2H),5.33(d,J＝4.2Hz,2H),5.20(s,2H),5.10(d,J＝3.1Hz,2H),4.98–4.83(m,6H),4.46(t,J＝5.7Hz,2H),4.17(d,J＝7.8Hz,2H),3.99(d,J＝10.4Hz,2H),3.70–3.54(m,4H),3.46–3.39(m,4H),3.28–3.19(m,6H),3.14–3.09(m,2H),3.05(s,4H),2.95(td,J＝8.3,4.4Hz,2H),1.99(d,J＝10.0Hz,12H)； 13 C NMR(100MHz,DMSO)δ166.16,144.59,139.88,136.91,135.95,131.98,125.27,123.90,103.07,94.52,76.86,76.75,76.27,76.25,73.44,72.44,69.96,69.22,67.92,60.97,12.67,12.55；HRMS(MALDI)calcd for C 44 H 64 NaO 24 [M+Na] + 999.3680,found 999.3677。
compound 2: saffron glycoside-2: mp is 201-203 ℃; 1 H NMR(400MHz,DMSO)δ7.36(d,J＝11.2Hz,1H),6.90–6.84(m,2H),6.81(d,J＝2.9Hz,1H),6.72–6.63(m,2H),6.54(d,J＝8.3Hz,1H),5.42(d,J＝7.7Hz,2H),5.31(dd,J＝11.3,4.8Hz,2H),5.19(d,J＝3.4Hz,1H),5.14–5.08(m,2H),5.03(d,J＝5.1Hz,1H),4.94(d,J＝4.5Hz,1H),4.90(d,J＝1.8Hz,1H),4.86(d,J＝4.7Hz,1H),4.59(t,J＝5.9Hz,1H),4.46(t,J＝5.9Hz,1H),4.18(d,J＝7.8Hz,1H),3.99(d,J＝10.4Hz,1H),3.79(d,J＝11.3Hz,1H),3.68–3.62(m,3H),3.59(dd,J＝11.2,5.2Hz,1H),3.47–3.41(m,3H),3.27–3.21(m,6H),3.19–3.10(m,3H),3.06(s,2H),2.96(td,J＝8.3,4.8Hz,1H),1.99(d,J＝9.5Hz,12H)； 13 C NMR(100MHz,DMSO)δ166.15,144.56,144.49,139.84,139.74,136.87,135.91,131.95,125.34,125.27,123.87,103.06,94.57,94.52,77.82,76.84,76.74,76.44,76.26,73.44,72.51,72.44,72.42,69.96,69.50,69.23,67.92,60.96,60.54,12.64,12.53；HRMS(MALDI)calcd for C 38 H 54 NaO 19 [M+Na] + 837.3152,found 837.3149。
example 2
Synthesis and structural characterization of crocetin:
saffron glycoside-1 (2.00 g,2.05 mmol) was dissolved in 100mL of water, an aqueous solution of sodium hydroxide (2.00 g,50 mmol) was added, and the mixture was heated to 100deg.C with stirring to react for three hours; after cooling, 2M hydrochloric acid was added to adjust the pH of the reaction solution to approximately 2. Suction filtration and water washing of the filter cake to obtain crude crocetin (0.60 g,1.83 mmol) mp>320℃； 1 H NMR(400MHz,DMSO)δ7.20(d,J＝10.5Hz,1H),6.83(d,J＝6.6Hz,1H),6.72(d,J＝14.7Hz,1H),6.63(d,J＝11.5Hz,1H),6.49(d,J＝5.5Hz,1H),1.97(s,3H),1.92(s,3H)； 13 C NMR(100MHz,DMSO)δ169.65,143.64,138.31,137.08,135.68,132.04,127.68,124.58,13.28,13.00。
Example 3
Synthesis and structural characterization of crocetin diester:
the crude crocetin (0.20 g,0.61 mmol) was dissolved in DMF (50 mL), DBU (0.37 g,2.44 mmol) and bromohydrocarbon (2.44 mmol) were then added, stirred at room temperature for 24-96h, water and dichloromethane were added, the aqueous phase was washed twice with dichloromethane, the organic phases were combined, washed three times with water, washed once with saturated saline, dried over anhydrous magnesium sulfate, suction filtered, desolventized and silica gel column chromatography to give the target product (3-19).
Compound 3:
Figure BDA0004044202910000031
Yield:65.3％；mp 214–216℃； 1 H NMR(400MHz,CDCl 3 )δ7.29(d,J＝10.6Hz,2H),
6.76–6.66(m,2H),6.66–6.50(m,4H),6.42–6.31(m,2H),3.77(s,6H),2.00(d,J＝4.2Hz,12H)； 13 C NMR(100MHz,CDCl 3 )δ168.90,143.73,138.86,136.70,135.32,131.31,126.44,123.80,51.79,12.88,12.77；HRMS(MALDI)calcd for C 22 H 28 O 4 [M]+356.1988,found 356.1980。
compound 4:
Figure BDA0004044202910000032
Yield:58.5％；mp 205–207℃； 1 H NMR(400MHz,CDCl 3 )δ7.29(d,J＝10.9Hz,2H),
6.73–6.51(m,6H),6.37(d,J＝7.6Hz,2H),4.22(dd,J＝14.0,7.0Hz,4H),2.00(s,12H),1.32(t,J＝7.0Hz,6H)； 13 C NMR(100MHz,CDCl 3 )δ168.60,143.71,138.70,136.85,135.37,131.41,126.93,124.00,60.68,14.49,13.01,12.93；HRMS(MALDI)calcd for C 24 H 32 O 4 [M] + 384.2301,found 384.2293。
compound 5:
Figure BDA0004044202910000033
Yield:42.4％；mp 152–153℃； 1 H NMR(400MHz,CDCl 3 )δ7.28(d,J＝11.7Hz,2H),6.70
(dd,J＝7.8,2.2Hz,2H),6.65–6.50(m,4H),6.37(d,J＝7.6Hz,2H),4.17(t,J＝6.5Hz,4H),2.00(s,12H),1.67(dd,J＝14.5,6.9Hz,4H),1.43(dd,J＝14.7,7.5Hz,4H),0.96(t,J＝7.3Hz,6H)； 13 C NMR(100MHz,CDCl 3 )δ168.52,143.56,138.53,136.69,135.21,131.26,126.86,123.86,64.47,30.84,19.28,13.76,12.87,12.78；HRMS(MALDI)calcd for C 28 H 40 O 4 [M] + 440.2927,found 440.2919。
compound 6:
Figure BDA0004044202910000034
Yield:29.9％；mp 190–192℃； 1 H NMR(400MHz,CDCl 3 )δ7.35(d,J＝11.1Hz,2H),
6.75–6.51(m,6H),6.38(d,J＝8.1Hz,2H),4.52(dd,J＝12.5,2.4Hz,2H),4.01(dd,J＝12.3,6.3Hz,2H),3.31–3.26(m,2H),2.88(t,J＝4.4Hz,2H),2.71–2.67(m,2H),2.02(s,6H),2.00(s,6H)； 13 C NMR(100MHz,CDCl 3 )δ168.14,144.29,139.68,136.87,135.71,131.56,125.99,123.83,65.25,49.73,44.82,12.98,12.90；HRMS(MALDI)calcd for C 26 H 32 O 6 [M] + 440.2199,found440.2191。
compound 7:
Figure BDA0004044202910000041
Yield:45.3％；mp 231–232℃； 1 H NMR(400MHz,CDCl 3 )δ7.37(d,J＝11.2Hz,2H),
6.77–6.66(m,4H),6.58(d,J＝11.6Hz,2H),6.42(d,J＝6.6Hz,2H),4.82(s,4H),2.02(s,6H),2.01(s,6H)； 13 C NMR(100MHz,CDCl 3 )δ166.70,145.59,141.62,137.04,136.50,131.96,124.21,123.58,114.92,48.71,12.94,12.88；HRMS(MALDI)calcd for C 24 H 26 N 2 O 4 [M] + 406.1893,found 406.1885。
compound 8:
Figure BDA0004044202910000042
Yield:49.8％；mp 158–160℃； 1 H NMR(400MHz,CDCl 3 )δ7.24(d,J＝4.4Hz,2H),6.68(d,
J＝8.0Hz,2H),6.63–6.48(m,6H),6.36(d,J＝8.1Hz,2H),3.84(s,4H),1.98(s,6H),1.98(s,6H),0.09(s,18H)； 13 C NMR(100MHz,CDCl 3 )δ169.40,143.65,138.53,136.82,135.32,131.39,127.08,123.97,57.91,13.14,12.93,-2.81；HRMS(MALDI)calcd for C 28 H 44 O 4 Si 2 [M] + 500.2778,found 500.2770。
compound 9:
Figure BDA0004044202910000043
Yield:42.5％；mp 162–163℃； 1 H NMR(400MHz,CDCl 3 )δ7.39(d,J＝10.8Hz,2H),
6.75–6.52(m,6H),6.38(d,J＝6.6Hz,2H),4.72(s,4H),3.78(s,6H),2.04(s,6H),2.00(s,6H)； 13 C NMR(100MHz,CDCl 3 )δ168.62,167.62,144.46,140.20,136.79,135.70,131.50,125.38,123.70,60.84,52.16,12.82,12.77；HRMS(MALDI)calcd for C 26 H 32 O 8 [M] + 472.2097,found472.2089。
compound 10:
Figure BDA0004044202910000044
Yield:24.04％；mp 175–177℃； 1 H NMR(400MHz,CDCl 3 )δ7.37(d,J＝10.4Hz,2H),
6.79–6.50(m,6H),6.40(s,2H),5.85(s,4H),2.12(s,6H),2.01(s,12H)； 13 C NMR(100MHz,CDCl 3 )δ169.79,166.87,144.82,140.65,136.83,135.94,131.61,125.18,123.65,79.51,20.81,12.77,12.70；HRMS(MALDI)calcd for C 26 H 32 O 8 [M] + 472.2097,found 472.2089。
compound 11:
Figure BDA0004044202910000051
Yield:45.4％；mp 189–191℃； 1 H NMR(400MHz,CDCl 3 )δ7.33(d,J＝10.7Hz,2H),
6.74–6.50(m,6H),6.37(d,J＝7.7Hz,2H),5.99(ddt,J＝16.2,10.7,5.5Hz,2H),5.35(d,J＝17.2Hz,2H),5.25(d,J＝10.4Hz,2H),4.68(d,J＝5.2Hz,4H),2.02(s,6H),1.99(s,6H)； 13 C NMR(100MHz,CDCl 3 )δ168.18,143.98,139.16,136.87,135.52,132.79,131.49,126.59,123.95,117.92,65.37,13.02,12.93；HRMS(MALDI)calcd for C 26 H 32 O 4 [M] + 408.2301,found 408.2293。
compound 12:
Figure BDA0004044202910000052
Yield:62.3％；mp 157–159℃； 1 H NMR(400MHz,CDCl 3 )δ7.35(d,J＝10.7Hz,2H),
6.75–6.51(m,6H),6.38(d,J＝7.1Hz,2H),4.78(s,4H),2.48(s,2H),2.02(s,6H),2.00(s,6H)； 13 C NMR(100MHz,CDCl 3 )δ167.54,144.35,139.88,136.80,135.67,131.50,125.67,123.72,78.19,74.58,52.11,12.84,12.80；HRMS(MALDI)calcd for C 26 H 28 O 4 [M] + 404.1988,found404.1980。
compound 13:
Figure BDA0004044202910000053
Yield:41.9％；mp 183–185℃； 1 H NMR(400MHz,CDCl 3 )δ7.37–7.27(m,4H),6.98(d,J＝
7.4Hz,2H),6.94(s,2H),6.87(d,J＝8.2Hz,2H),6.70(d,J＝10.4Hz,2H),6.59(dd,J＝21.2,12.8Hz,4H),6.36(d,J＝7.7Hz,2H),5.19(s,4H),3.82(s,6H),2.03(s,6H),1.99(s,6H)； 13 CNMR(100MHz,CDCl 3 )δ168.32,159.87,144.08,139.34,138.15,136.87,135.57,131.50,129.72,126.49,123.92,120.34,113.69,113.60,66.32,55.39,13.08,12.92；HRMS(MALDI)calcd for C 36 H 40 O 6 [M] + 568.2825,found 568.2816。
compound 14:
Figure BDA0004044202910000054
Yield:41.5％；mp 167–169℃； 1 H NMR(400MHz,CDCl 3 )δ7.24–7.17(m,6H),7.00(t,J＝
8.6Hz,4H),6.71(dd,J＝7.9,2.4Hz,2H),6.63–6.49(m,4H),6.38(d,J＝7.8Hz,2H),4.34(t,J＝6.8Hz,4H),2.97(t,J＝6.8Hz,4H),1.99(s,6H),1.97(s,6H)； 13 C NMR(100MHz,CDCl 3 )δ168.28,162.93,160.51,143.85,138.97,136.73,135.43,133.82,133.79,131.38,130.42,130.34,126.46,123.79,115.38,115.17,65.03,34.50,12.85,12.79；HRMS(MALDI)calcd for C 36 H 38 F 2 O 4 [M] + 572.2738,found 572.2729。
compound 15:
Figure BDA0004044202910000061
Yield:30.3％；mp 164–165℃； 1 H NMR(400MHz,CDCl 3 )δ7.58(d,J＝7.8Hz,4H),7.37(d,
J＝7.8Hz,4H),7.24(d,J＝10.5Hz,2H),6.72(dd,J＝7.9,2.3Hz,2H),6.63–6.48(m,4H),6.38(d,J＝7.4Hz,2H),4.40(t,J＝6.7Hz,4H),3.06(t,J＝6.6Hz,4H),1.99(s,6H),1.97(s,6H)； 13 CNMR(100MHz,CDCl 3 )δ168.21,143.96,142.35,139.12,136.72,135.49,131.41,129.29,126.28,125.45,125.42,125.38,125.34,123.73,64.46,35.10,29.70,12.83,12.78；HRMS(MALDI)calcd for C 38 H 38 F 6 O 4 [M] + 672.2674,found 672.2665。
compound 16:
Figure BDA0004044202910000062
Yield:47.9％；mp 186–188℃； 1 H NMR(400MHz,CDCl 3 )δ8.60(d,J＝4.3Hz,2H),7.71
(td,J＝7.7,1.3Hz,2H),7.42–7.38(m,4H),7.26–7.21(m,2H),6.71(dd,J＝7.9,2.7Hz,2H),6.59(dt,J＝15.0,12.9Hz,4H),6.38(d,J＝8.7Hz,2H),5.34(s,4H),2.06(s,6H),2.00(s,6H)； 13 CNMR(100MHz,CDCl 3 )δ167.98,156.42,149.40,144.15,139.55,136.76,136.74,135.55,131.42,126.08,123.76,122.72,121.64,66.94,12.95,12.79；HRMS(MALDI)calcd for C 32 H 34 N 2 O 4 [M+H] + 511.2591,found 511.2588。
compound 17:
Figure BDA0004044202910000063
Yield:47.3％；mp 183–184℃； 1 H NMR(400MHz,CDCl 3 )δ7.27(d,J＝9.1Hz,2H),7.08(s,
2H),6.98(d,J＝7.8Hz,2H),6.76–6.67(m,4H),6.64–6.50(m,4H),6.42–6.32(m,2H),4.55(t,J＝8.6Hz,4H),4.31(t,J＝6.9Hz,4H),3.19(t,J＝8.6Hz,4H),2.92(t,J＝6.9Hz,4H),1.99(s,12H)； 13 C NMR(100MHz,CDCl 3 )δ168.35,158.82,143.70,138.82,136.72,135.32,131.33,129.95,128.51,127.18,126.66,125.46,123.85,109.08,71.19,65.59,34.73,29.78,12.87,12.79；HRMS(MALDI)calcd for C 40 H 44 O 6 [M] + 620.3138,found 620.3128。
compound 18:
Figure BDA0004044202910000064
Yield:46.2％；mp 143–145℃； 1 H NMR(400MHz,CDCl 3 )δ7.32–7.26(m,6H),6.95(t,J＝
7.6Hz,2H),6.91(d,J＝8.1Hz,4H),6.70(dd,J＝8.0,2.5Hz,2H),6.64–6.50(m,4H),6.37(d,J＝8.4Hz,2H),4.37(t,J＝6.2Hz,4H),4.09(t,J＝6.1Hz,4H),2.19(p,J＝6.2Hz,4H),2.02–1.96(m,12H)； 13 C NMR(100MHz,CDCl 3 )δ168.48,158.94,143.95,139.02,136.86,135.50,131.47,129.60,126.63,123.92,120.92,114.65,64.58,61.64,28.97,13.03,12.93；HRMS(MALDI)calcd for C 38 H 44 O 6 [M] + 596.3138,found 596.3129。
compound 19:
Figure BDA0004044202910000071
Yield:48.6％；mp 205–206℃； 1 H NMR(400MHz,CDCl 3 )δ7.84(dd,J＝4.9,3.2Hz,4H),
7.72–7.68(m,4H),7.24(d,J＝10.2Hz,2H),6.72(d,J＝10.0Hz,2H),6.58–6.46(m,4H),6.37(d,J＝8.5Hz,2H),4.23(t,J＝5.9Hz,4H),3.85(t,J＝6.7Hz,4H),2.16–2.08(m,4H),1.99(s,6H),1.97(s,6H)； 13 C NMR(100MHz,CDCl 3 )δ168.24,168.19,143.77,138.91,136.70,135.30,133.93,132.15,131.31,126.39,123.77,123.25,62.10,35.34,27.77,12.78；HRMS(MALDI)calcd for C 42 H 42 N 2 O 8 [M] + 702.2941,found 702.2931。
example 4
Biological activity is exemplified by anti-tobacco mosaic virus (Tobacco mosaic virus, TMV) activity,
1. virus purification and concentration determination:
the virus purification and concentration measurement are carried out by compiling tobacco mosaic virus SOP standard according to a measuring room generated by elements of university of south China. After 2 times of polyethylene glycol centrifugation treatment, the concentration of the virus crude extract is measured, and the virus crude extract is refrigerated at 4 ℃ for standby.
2. Compound solution preparation:
after weighing, adding DMF to dissolve the raw materials to obtain 1×10 5 Mu g/mL mother liquor, and then diluting the mother liquor to the required concentration by using an aqueous solution containing 1 per mill of Tween 80; the ribavirin preparation is directly diluted with water.
3. Living body protecting action:
3-5 She Qishan Xiyan with uniform growth vigor is selected, the whole plant is sprayed and applied, each treatment is repeated for 3 times, and 1 permillage of Tween 80 aqueous solution is used for comparison. After 24h, the leaf surface is spread with silicon carbide (500 meshes), the whole leaf surface is dipped with a virus liquid by a writing brush, the whole leaf surface is lightly rubbed for 2 times along the branch pulse direction, the lower part of the leaf surface is supported by a palm, the virus concentration is 10 mug/mL, and the leaf surface is washed by running water after inoculation. And after 3d, recording the number of the lesions, and calculating the control effect.
4. In vivo therapeutic action:
3-5 She Qishan Xiyan with uniform growth vigor is selected, the whole leaf of the writing brush is inoculated with virus, the virus concentration is 10 mug/mL, and the whole leaf is washed by running water after inoculation. After leaf surface is dried, spraying and applying the whole plant, repeating for 3 times every treatment, and setting 1%Tween 80 water solution as a control. And after 3d, recording the number of the lesions, and calculating the control effect.
5. In vivo passivation:
selecting 3-5 She Qishan Xie smoke with uniform growth vigor, mixing the medicament with an equal volume of virus juice, inactivating for 30min, performing friction inoculation, wherein the virus concentration is 20 mug/mL, washing with running water after inoculation, repeating for 3 times, and setting 1 milltween 80 water solution for comparison. And counting the number of lesions after 3d, and calculating a result.
Inhibition ratio (%) = [ (control number of dried spots-treated number of dried spots)/control number of dried spots ] ×100%
TABLE 1 results of in vivo tests of crocetin diester against tobacco mosaic Virus (0.5 mg/mL) a
Figure BDA0004044202910000081
When the in vivo inactivation activity of the tested compound is higher than 40%, the in vivo protection and in vivo therapeutic effect of the compound is tested.
It can be seen from Table 1 that all compounds showed activity against tobacco mosaic virus at a concentration of 0.5 mg/mL. The natural products saffron glycoside-1 and saffron glycoside-2 exhibit activity levels significantly higher than commercial varieties of ribavirin. Most of the synthetic crocetin diester derivatives showed good in vivo anti-TMV activity, and compounds 5,9,13,14 and 15 showed higher levels of activity than ribavirin, in particular compound 14. Compounds 3-5 containing linear alkyl chains have moderate anti-TMV activity, but their passivation effect is less than 40%. The alkyl chain has a greater effect on TMV activity when it is linked to different functional groups (compounds 6-12). Compound 9, bearing methoxy functionality, exhibited a higher level of activity than ribavirin. When substituted benzene ring is introduced into alkyl chain through C-C bond, anti-TMV activity (inhibition rate: compound 13> compound 3; compound 14> compound 15> compound 4) can be improved, and crocetin di (4-fluorobenzene ethyl) ester (compound 14) shows highest anti-TMV activity in the synthesized crocetin diester and is higher than that of the lead compounds safflor-1 and safflor-2. However, the introduction of the heteroaromatic ring does not increase the anti-TMV activity.

Claims (2)

1. The application of the saffron glycoside-1 and the saffron glycoside-2 is characterized in that natural products of the saffron glycoside-1 and the saffron glycoside-2 are used as active lead compounds, and pesticides for resisting tobacco mosaic virus are synthesized through a structure-activity relationship.
2. The application of the crocin-1 and the crocin-2 is characterized in that the crocin-1 and the crocin-2 are directly used for resisting tobacco mosaic virus and preventing and treating the tobacco mosaic virus.
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