CN118754852A - Novel dihydroisoquinolinone compounds and their use in preparing anti-plant pathogenic fungicides - Google Patents
Novel dihydroisoquinolinone compounds and their use in preparing anti-plant pathogenic fungicides Download PDFInfo
- Publication number
- CN118754852A CN118754852A CN202410836936.1A CN202410836936A CN118754852A CN 118754852 A CN118754852 A CN 118754852A CN 202410836936 A CN202410836936 A CN 202410836936A CN 118754852 A CN118754852 A CN 118754852A
- Authority
- CN
- China
- Prior art keywords
- formula
- compound
- substituted
- nmr
- plant pathogenic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000417 fungicide Substances 0.000 title claims abstract description 10
- WGLUNLJVYNJMBU-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-n-[(3-methyl-1-oxo-2,4-dihydroisoquinolin-3-yl)methyl]decanamide Chemical class C1=CC=C2C(=O)NC(CN(CCN(C)C)C(=O)CCCCCCCCC)(C)CC2=C1 WGLUNLJVYNJMBU-UHFFFAOYSA-N 0.000 title description 10
- 230000001717 pathogenic effect Effects 0.000 title description 3
- -1 dihydroisoquinolinone compound Chemical class 0.000 claims abstract description 13
- 244000053095 fungal pathogen Species 0.000 claims abstract description 9
- 230000000855 fungicidal effect Effects 0.000 claims abstract description 5
- 244000000004 fungal plant pathogen Species 0.000 claims abstract description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 241000223602 Alternaria alternata Species 0.000 claims description 3
- 241000213004 Alternaria solani Species 0.000 claims description 3
- 241001529387 Colletotrichum gloeosporioides Species 0.000 claims description 3
- 241000223195 Fusarium graminearum Species 0.000 claims description 3
- 125000001931 aliphatic group Chemical group 0.000 claims description 3
- 239000004305 biphenyl Chemical group 0.000 claims description 3
- 235000010290 biphenyl Nutrition 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 241001115351 Physalospora Species 0.000 claims description 2
- 241001361634 Rhizoctonia Species 0.000 claims description 2
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 42
- 239000000575 pesticide Substances 0.000 abstract description 4
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 abstract 1
- 229940002612 prodrug Drugs 0.000 abstract 1
- 239000000651 prodrug Substances 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 37
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 23
- 239000007787 solid Substances 0.000 description 20
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical class C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000012141 concentrate Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- TWFZGCMQGLPBSX-UHFFFAOYSA-N Carbendazim Natural products C1=CC=C2NC(NC(=O)OC)=NC2=C1 TWFZGCMQGLPBSX-UHFFFAOYSA-N 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 239000006013 carbendazim Substances 0.000 description 4
- JNPZQRQPIHJYNM-UHFFFAOYSA-N carbendazim Chemical compound C1=C[CH]C2=NC(NC(=O)OC)=NC2=C1 JNPZQRQPIHJYNM-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 239000005747 Chlorothalonil Substances 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 241000233866 Fungi Species 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 240000008042 Zea mays Species 0.000 description 3
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 3
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 3
- CRQQGFGUEAVUIL-UHFFFAOYSA-N chlorothalonil Chemical compound ClC1=C(Cl)C(C#N)=C(Cl)C(C#N)=C1Cl CRQQGFGUEAVUIL-UHFFFAOYSA-N 0.000 description 3
- 235000005822 corn Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000012085 test solution Substances 0.000 description 3
- OPHQOIGEOHXOGX-UHFFFAOYSA-N 3,4,5-trimethoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC(OC)=C1OC OPHQOIGEOHXOGX-UHFFFAOYSA-N 0.000 description 2
- UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 241000223218 Fusarium Species 0.000 description 2
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 2
- 206010027146 Melanoderma Diseases 0.000 description 2
- 208000031888 Mycoses Diseases 0.000 description 2
- 235000014443 Pyrus communis Nutrition 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 240000003768 Solanum lycopersicum Species 0.000 description 2
- 241000209140 Triticum Species 0.000 description 2
- 235000021307 Triticum Nutrition 0.000 description 2
- 150000001263 acyl chlorides Chemical class 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000003592 biomimetic effect Effects 0.000 description 2
- 235000021393 food security Nutrition 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 241000234270 Amaryllidaceae Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000218164 Menispermaceae Species 0.000 description 1
- 241000218180 Papaveraceae Species 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000005842 Thiophanate-methyl Substances 0.000 description 1
- KEIZXGINFPDITQ-UHFFFAOYSA-N UNPD138008 Natural products C1=C(O)C(OC)=CC=C1C1=C(OC2C(C(O)C(O)C(COC3C(C(O)C(O)C(C)O3)O)O2)O)C(=O)C2=C(O)C=C(O)C=C2O1 KEIZXGINFPDITQ-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125890 compound Ia Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 244000000037 crop pathogen Species 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- UIDGLYUNOUKLBM-GEBJFKNCSA-N isorhamnetin-3-O-rutinoside Chemical compound C1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO[C@H]3[C@@H]([C@H](O)[C@@H](O)[C@H](C)O3)O)O2)O)=C1 UIDGLYUNOUKLBM-GEBJFKNCSA-N 0.000 description 1
- BGLPQQKZNUKSAR-UHFFFAOYSA-N isorhamnetin-3-O-rutinoside Natural products COc1ccc(cc1O)C2=C(OC3OC(COCC4OC(O)C(O)C(O)C4O)C(O)C(O)C3O)C(=O)c5c(O)cc(O)cc5O2 BGLPQQKZNUKSAR-UHFFFAOYSA-N 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- IEPKWJCBNGNVDF-UHFFFAOYSA-N narcissin Natural products OC1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)OC2C(C(O)C(O)C(COC3C(C(O)C(O)C(C)O3)O)O2)O)=C1 IEPKWJCBNGNVDF-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000000447 pesticide residue Substances 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- QGHREAKMXXNCOA-UHFFFAOYSA-N thiophanate-methyl Chemical compound COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC QGHREAKMXXNCOA-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- 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
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
- A01N43/42—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings condensed with carbocyclic rings
-
- 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
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/50—1,3-Diazoles; Hydrogenated 1,3-diazoles
-
- 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
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
-
- 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
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Plant Pathology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pest Control & Pesticides (AREA)
- Wood Science & Technology (AREA)
- Agronomy & Crop Science (AREA)
- Health & Medical Sciences (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Mycology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
本发明涉及农药领域和植物保护领域。具体来说,涉及一种新型二氢异喹啉酮类化合物,包括其立体异构体、前药分子、药学上可接受的盐,及其该类分子作为制备抗植物病原真菌杀菌剂的应用。此类异喹啉化合物的结构如式(I):本发明所述化合物对多种植物病原真菌的具有显著的抑制活性,可用于制备杀菌剂。The present invention relates to the field of pesticides and plant protection. Specifically, it relates to a novel dihydroisoquinolinone compound, including its stereoisomers, prodrug molecules, pharmaceutically acceptable salts, and the use of such molecules as a fungicide for preparing anti-plant pathogenic fungi. The structure of such isoquinoline compounds is as shown in formula (I): The compound of the invention has significant inhibitory activity against various plant pathogenic fungi and can be used for preparing fungicides.
Description
技术领域Technical Field
本发明涉及农药领域和植物保护领域,尤其是新型二氢异喹啉酮类化合物及其作为制备抗植物病原真菌杀菌剂的应用。The invention relates to the field of pesticides and plant protection, in particular to novel dihydroisoquinolinone compounds and applications thereof in preparing anti-plant pathogenic fungicide.
背景技术Background Art
植物病原真菌是导致农作物减产欠收的主要因素之一,并且其分泌的多种代谢产物具有严重的毒副作用,已严重威胁粮食安全。由于农作物抗性品种匮乏、生物防治见效缓慢,化学杀菌剂仍是防治农作物真菌病害的主要手段。然而,随着化学杀菌剂的长期大量使用,农药残留、真菌的抗药性等问题日益暴露,亟需创制新型的绿色农药用以防治植物真菌病害,保障粮食安全。Plant pathogenic fungi are one of the main factors leading to crop yield reduction and poor harvest, and the various metabolites they secrete have serious toxic side effects, which have seriously threatened food security. Due to the lack of crop resistant varieties and the slow effectiveness of biological control, chemical fungicides are still the main means of preventing and controlling fungal diseases of crops. However, with the long-term and large-scale use of chemical fungicides, problems such as pesticide residues and fungal resistance have become increasingly exposed. There is an urgent need to create new green pesticides to prevent and control plant fungal diseases and ensure food security.
异喹啉酮类生物碱是自然界中一类常见的含氮杂环天然产物,主要分布于罂粟科、石蒜科、防己科等植物。异喹啉酮类生物碱结构类型多样,具有显著的生物活性,如具有强效抗癌活性的水鬼蕉碱,抗肿瘤活性的水仙环素等。近年来,围绕异喹啉酮类生物碱的结构优化和生物活性筛选一直是新药开发的重点。另外,异喹啉酮骨架也是构成药物分子的重要活性单元,存在于多种医药分子和农药化学品中。基于前期研究结果,申请人采用仿生合成策略,以异喹啉酮为活性母核,通过药效团拼接和生物电子等排的原理,设计并合成了一系列结构新颖的二氢异喹啉酮类化合物。结果证明,本发明中所涉及的二氢异喹啉酮类化合物对多种植物病原真菌具有抑菌活性。Isoquinolinone alkaloids are a common type of nitrogen-containing heterocyclic natural products in nature, mainly distributed in plants such as Papaveraceae, Amaryllidaceae, and Menispermaceae. Isoquinolinone alkaloids have diverse structural types and significant biological activities, such as aquabine with strong anticancer activity and narcissin with antitumor activity. In recent years, the structural optimization and biological activity screening of isoquinolinone alkaloids have always been the focus of new drug development. In addition, the isoquinolinone skeleton is also an important active unit that constitutes drug molecules and exists in a variety of pharmaceutical molecules and pesticide chemicals. Based on the results of previous studies, the applicant adopted a biomimetic synthesis strategy, using isoquinolinone as the active parent nucleus, and designed and synthesized a series of novel dihydroisoquinolinone compounds through the principle of pharmacophore splicing and bioisostericity. The results show that the dihydroisoquinolinone compounds involved in the present invention have antibacterial activity against a variety of plant pathogenic fungi.
本发明所涉及的新型二氢异喹啉酮类化合物都为未见文献报道的新化合物。本专利是申请人首次对此类二氢异喹啉酮类化合物的抗植物病原真菌活性报道。The novel dihydroisoquinolinone compounds involved in the present invention are all new compounds that have not been reported in the literature. This patent is the first report by the applicant on the anti-plant pathogenic fungi activity of such dihydroisoquinolinone compounds.
发明内容Summary of the invention
本发明目的在于提供新型二氢异喹啉酮类化合物及其作为制备抗植物病原真菌杀菌剂的应用。The present invention aims to provide novel dihydroisoquinolinone compounds and their application in preparing anti-plant pathogenic fungicide.
本发明所述的新型二氢异喹啉酮类化合物,其结构通式如式(I),The novel dihydroisoquinolinone compounds of the present invention have a general structural formula as shown in formula (I):
式(I)中,R2选自取苯基、联苯基、萘基、吡啶基、噻吩基、呋喃基、吡唑基和噻唑基等芳香基团,结构如式(II)所示,In formula (I), R 2 is selected from aromatic groups such as phenyl, biphenyl, naphthyl, pyridyl, thienyl, furyl, pyrazolyl and thiazolyl, and the structure is shown in formula (II).
式(II)中,R8选自氢、卤素、硝基、二氟甲基、三氟甲基、C1-C6直链或支链烷基和C1-C6直链或支链烷氧基、N,N-二甲基;或者相邻的两个R8和与其相连接的芳环上的碳原子一起形成五元或者六元脂肪环、脂氧杂环;n为1-5的整数。In formula (II), R 8 is selected from hydrogen, halogen, nitro, difluoromethyl, trifluoromethyl, C 1 -C 6 straight chain or branched alkyl and C 1 -C 6 straight chain or branched alkoxy, N,N-dimethyl; or two adjacent R 8 and the carbon atoms on the aromatic ring connected thereto form a five-membered or six-membered aliphatic ring or aliphatic oxygen heterocycle; n is an integer of 1-5.
式(I)中,的R3选自C1-C6直链或支链烷基、烷氧基取代的C2-C6直链或支链烷基、取代或未取代的苯基、取代或未取代的吡啶基、取代或未取代的咪唑基、取代或未取代的嘧啶基。In formula (I), R 3 is selected from C 1 -C 6 straight or branched alkyl, alkoxy-substituted C 2 -C 6 straight or branched alkyl, substituted or unsubstituted phenyl, substituted or unsubstituted pyridyl, substituted or unsubstituted imidazolyl, substituted or unsubstituted pyrimidinyl.
式(I)中,R4-R7选自氢、卤素、硝基、二氟甲基、三氟甲基、C1-C6直链或支链烷基、C1-C6直链或支链烷氧基、N,N-二甲基。In formula (I), R 4 - R 7 are selected from hydrogen, halogen, nitro, difluoromethyl, trifluoromethyl, C 1 -C 6 straight chain or branched chain alkyl, C 1 -C 6 straight chain or branched chain alkoxy, and N,N-dimethyl.
本发明提供了所述新型二氢异喹啉酮类化合物I的通用制备方法,其典型合成路线如下:The present invention provides a general preparation method of the novel dihydroisoquinolinone compound I, and its typical synthesis route is as follows:
化合物I作为制备抗植物病原真菌药物的应用。生物活性测试表明,目标化合物对苹果炭疽病(Colletotrichum gloeosporioides)、小麦赤霉病菌(Fusariumgraminearum)、番茄早疫病菌(Alternaria solani)、苹果轮纹病菌(Physalosporapiricola)、玉米纹枯病菌(RhizoctoniasolanikOhn)和梨黑斑病菌(Alternariaalternata)等具有显著的抑制活性。Compound I is used as a drug for preparing anti-plant pathogenic fungi. Biological activity tests show that the target compound has significant inhibitory activity against apple anthracnose (Colletotrichum gloeosporioides), wheat fusarium (Fusarium graminearum), tomato early blight (Alternaria solani), apple ring rot (Physalosporapiricola), corn sheath blight (Rhizoctonia solanikOhn ) and pear black spot (Alternaria alternata).
与现有技术相比,本发明具有如下优点和效果:Compared with the prior art, the present invention has the following advantages and effects:
本发明是以天然异喹啉酮类生物碱为先导化合物,对其结构进行合理的仿生优化,采用活性药效团拼接和生物电子等排的原理,将异喹啉酮与酰胺进行拼接,采用简洁高效的合成路线,得到一系列新型的二氢异喹啉酮类化合物。进一步通过抑菌活性测试,结果显示该类化合物的抗植物病原真菌活性显著,部分目标化合物优于商品化杀菌剂百菌清或多菌灵,为异喹啉酮类化合物的合成和更广泛的生物活性研究提供基础资料。The present invention uses natural isoquinolinone alkaloids as lead compounds, performs reasonable biomimetic optimization on their structures, adopts the principles of active pharmacophore splicing and bioisostericity, splices isoquinolinone with amide, and adopts a simple and efficient synthetic route to obtain a series of novel dihydroisoquinolinone compounds. Further antibacterial activity tests show that the anti-plant pathogenic fungi activity of the compounds is significant, and some target compounds are superior to commercial fungicides chlorothalonil or carbendazim, providing basic data for the synthesis of isoquinolinone compounds and more extensive biological activity research.
具体实施方式DETAILED DESCRIPTION
在本发明中,申请人设计合成的二氢异喹啉酮类化合物I的结构通式如下:In the present invention, the applicant designed and synthesized dihydroisoquinolinone compound I having the following general structural formula:
式(I)中,R2选自取苯基、联苯基、萘基、吡啶基、噻吩基、呋喃基、吡唑基和噻唑基等芳香基团,结构如式(II)所示,In formula (I), R 2 is selected from aromatic groups such as phenyl, biphenyl, naphthyl, pyridyl, thienyl, furyl, pyrazolyl and thiazolyl, and the structure is shown in formula (II).
式(II)中,R8选自氢、卤素、硝基、二氟甲基、三氟甲基、C1-C6直链或支链烷基和C1-C6直链或支链烷氧基、N,N-二甲基;或者相邻的两个R8和与其相连接的芳环上的碳原子一起形成五元或者六元脂肪环、脂氧杂环。In formula (II), R 8 is selected from hydrogen, halogen, nitro, difluoromethyl, trifluoromethyl, C 1 -C 6 straight chain or branched alkyl and C 1 -C 6 straight chain or branched alkoxy, N,N-dimethyl; or two adjacent R 8 and the carbon atoms on the aromatic ring connected thereto form a five-membered or six-membered aliphatic ring or aliphatic oxygen heterocycle.
式(I)中,的R3选自C1-C6直链或支链烷基、烷氧基取代的C2-C6直链或支链烷基、取代或未取代的苯基、取代或未取代的吡啶基、取代或未取代的咪唑基、取代或未取代的嘧啶基。,In formula (I), R 3 is selected from C 1 -C 6 straight chain or branched alkyl, alkoxy-substituted C 2 -C 6 straight chain or branched alkyl, substituted or unsubstituted phenyl, substituted or unsubstituted pyridyl, substituted or unsubstituted imidazolyl, substituted or unsubstituted pyrimidinyl.
式(I)中,R4-R7选自氢、卤素、硝基、二氟甲基、三氟甲基、C1-C6直链或支链烷基、C1-C6直链或支链烷氧基、N,N-二甲基。In formula (I), R 4 - R 7 are selected from hydrogen, halogen, nitro, difluoromethyl, trifluoromethyl, C 1 -C 6 straight chain or branched chain alkyl, C 1 -C 6 straight chain or branched chain alkoxy, and N,N-dimethyl.
本发明所述的异喹啉酮类化合物I的通用合成方法如反应式1所示,以化合物If进行具体说明。The general synthesis method of the isoquinolinone compound I of the present invention is shown in Reaction Scheme 1, and is specifically described using compound If.
实施例1,化合物If的合成。Example 1, Synthesis of Compound If.
化合物If的合成路线如反应式2所示。The synthetic route of compound If is shown in Reaction Scheme 2.
中间体3f的合成:将3,4,5-三甲氧基苯甲醛(3.0mmol,0.59g)和乙胺(6mmol,0.27g)溶于15mL干燥二氯甲烷中,室温反应,薄层色谱板(TLC)监测至反应完全。减压浓缩,向残余物中加入二氯甲烷(40mL),饱和食盐水萃取洗涤(10mL×3)至中性。收集有机相,无水硫酸钠干燥,抽滤,减压浓缩后直接投入下一步反应。Synthesis of intermediate 3f: 3,4,5-trimethoxybenzaldehyde (3.0mmol, 0.59g) and ethylamine (6mmol, 0.27g) were dissolved in 15mL dry dichloromethane, reacted at room temperature, and monitored by thin layer chromatography (TLC) until the reaction was complete. Concentrate under reduced pressure, add dichloromethane (40mL) to the residue, extract and wash with saturated brine (10mL×3) until neutral. Collect the organic phase, dry over anhydrous sodium sulfate, filter, concentrate under reduced pressure, and directly put into the next step reaction.
中间体4f的合成:将高酞酸酐(0.32g,2mmol)溶于15mL氯仿中,冷却至0℃。将亚胺中间体3f溶于5mL氯仿中,用恒压漏斗将其缓慢滴入高酞酸酐的氯仿溶液中,0℃反应,TLC监测至反应完全。减压浓缩,硅胶柱层析分离(二氯甲烷:甲醇=80:1)得到中间体4f。Synthesis of intermediate 4f: Dissolve perphthalic anhydride (0.32 g, 2 mmol) in 15 mL of chloroform and cool to 0°C. Dissolve the imine intermediate 3f in 5 mL of chloroform and slowly drip it into the chloroform solution of perphthalic anhydride using a constant pressure funnel. React at 0°C and monitor by TLC until the reaction is complete. Concentrate under reduced pressure and separate by silica gel column chromatography (dichloromethane: methanol = 80:1) to obtain intermediate 4f.
目标化合物If的合成方法:将中间体4f(0.39g,1mmol)和草酰氯(0.38g,3mmol)溶于15mL干燥二氯甲烷中,再加入一滴DMF,室温反应3h,TLC监测至反应完全。减压浓缩,得到的酰氯粗产物待用。将苯胺(0.09g,1mmol)和三乙胺(0.20g,2mmol)溶于10mL二氯甲烷中,冷却至0℃,将上述酰氯粗产物溶于干燥的二氯甲烷(5mL)中,用恒压漏斗将其缓慢滴入反应瓶,反应过夜,TLC监测至反应完全。减压浓缩,加入二氯甲烷(40mL),饱和食盐水萃取洗涤(10mL×3)。收集有机相,无水硫酸钠干燥,抽滤,柱层析(DCM:MeOH=80:1)分离得到目标化合物If。Synthesis of target compound If: Dissolve intermediate 4f (0.39 g, 1 mmol) and oxalyl chloride (0.38 g, 3 mmol) in 15 mL of dry dichloromethane, add one drop of DMF, react at room temperature for 3 h, and monitor the reaction until complete by TLC. Concentrate under reduced pressure, and the obtained crude acyl chloride product is set aside. Dissolve aniline (0.09 g, 1 mmol) and triethylamine (0.20 g, 2 mmol) in 10 mL of dichloromethane, cool to 0°C, dissolve the above crude acyl chloride product in dry dichloromethane (5 mL), slowly drip it into the reaction bottle with a constant pressure funnel, react overnight, and monitor the reaction until complete by TLC. Concentrate under reduced pressure, add dichloromethane (40 mL), extract and wash with saturated brine (10 mL×3). Collect the organic phase, dry over anhydrous sodium sulfate, filter, and separate by column chromatography (DCM:MeOH=80:1) to obtain the target compound If.
化合物If:产率58.1%,白色固体。1H NMR(400MHz,DMSO-d6)δ10.23(s,1H),7.97(dd,J=7.4,1.7Hz,1H),7.58(d,J=7.4Hz,2H),7.46–7.39(m,2H),7.34–7.29(m,3H),7.06(t,J=7.4Hz,1H),6.48(s,2H),5.13(d,J=1.7Hz,1H),4.17(d,J=1.7Hz,1H),3.94(dq,J=14.1,7.1Hz,1H),3.61(s,6H),3.59(s,3H),2.92(dq,J=14.0,7.0Hz,1H),1.08(t,J=7.1Hz,3H);13C NMR(100MHz,DMSO-d6)δ174.1,167.7,158.0,144.0,142.0,141.3,139.3,137.0,135.3,134.0,133.4,133.0,132.0,128.8,124.8,109.1,66.0,65.2,61.0,56.6,46.0,17.9.Compound If: yield 58.1%, white solid. 1 H NMR (400MHz, DMSO-d 6 ) δ10.23 (s, 1H), 7.97 (dd, J = 7.4, 1.7Hz, 1H), 7.58 (d, J = 7.4Hz, 2H), 7.46–7.39 (m, 2H), 7.34–7.29 (m, 3H), 7.06 (t, J = 7.4Hz, 1H), 6. 48(s,2H),5.13(d,J=1.7Hz,1H),4.17(d,J=1.7Hz,1H),3.94(dq,J=14.1,7.1Hz,1H),3.61(s,6H),3.59(s,3H),2.92(dq,J=14.0,7.0Hz,1H),1.08(t,J =7.1Hz,3H); 13 C NMR (100MHz, DMSO-d 6 ) δ174.1,167.7,158.0,144.0,142.0,141.3,139.3,137.0,135.3,134.0,133.4,133.0,132.0,128.8,124.8,109.1,66.0, 65.2,61.0,56.6,46.0,17.9.
其余目标化合物I的合成方法同If。The synthesis methods of the remaining target compounds I are the same as If.
根据实例1的制备方法,得到系列目标化合物Ia—Iu,其结构见表1。According to the preparation method of Example 1, a series of target compounds Ia-Iu were obtained, and their structures are shown in Table 1.
表1系列目标化合物I的结构式Table 1 Structural formula of series target compound I
化合物Ia:产率54.3%,白色固体。1H NMR(400MHz,DMSO-d6)δ8.14(t,J=5.5Hz,1H),7.95–7.89(m,1H),7.39–7.32(m,2H),7.14–7.09(m,1H),7.07–6.98(m,4H),5.04(d,J=1.8Hz,1H),3.97–3.91(m,2H),Compound Ia: Yield 54.3%, white solid. 1 H NMR (400 MHz, DMSO-d 6 ) δ8.14 (t, J=5.5 Hz, 1H), 7.95–7.89 (m, 1H), 7.39–7.32 (m, 2H), 7.14–7.09 (m, 1H), 7.07–6.98 (m, 4H), 5.04 (d, J=1.8 Hz, 1H), 3.97–3.91 (m, 2H),
3.36–3.31(m,2H),3.27–3.20(m,5H),2.80(dq,J=14.1,7.0Hz,1H),2.19(s,3H),1.04(t,J=7.1Hz,3H);13C NMR(100MHz,DMSO-d6)δ170.6,163.1,137.7,137.02,134.6,132.1,130.6,129.5,128.7,128.1,127.3,126.5,71.0,61.4,58.4,51.6,41.1,39.3,21.0,13.1.3.36–3.31(m,2H),3.27–3.20(m,5H),2.80(dq,J=14.1,7.0Hz,1H),2.19(s,3H),1.04(t,J=7.1Hz,3H) ; 13 C NMR (100MHz, DMSO-d 6 ) δ170.6,163.1,137.7,137.02,134.6,132.1,130.6,129.5,128.7,128.1,127.3,126.5,71.0,61.4,58.4,51.6,41.1,39. 3,21.0, 13.1.
化合物Ib:产率71.2%,白色固体。1H NMR(400MHz,DMSO-d6)δ10.32(s,1H),7.95(d,J=9.1Hz,1H),7.59(d,J=7.3Hz,2H),7.40–7.36(m,2H),7.31(t,J=7.9Hz,2H),7.23(d,J=8.8Hz,1H),7.11–7.03(m,5H),5.17(d,J=1.6Hz,1H),4.18(d,J=1.7Hz,1H),2.21(s,3H);13C NMR(100MHz,DMSO-d6)δ169.4,163.1,139.4,137.7,137.2,134.4,132.1,131.2,129.5,129.3,128.5,128.2,127.4,126.6,123.5,119.9,73.2,61.1,52.1,14.2.Compound Ib: yield 71.2%, white solid. 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.32 (s, 1H), 7.95 (d, J = 9.1 Hz, 1H), 7.59 (d, J = 7.3 Hz, 2H), 7.40-7.36 (m, 2H), 7.31 (t, J = 7.9 Hz, 2H), 7.23 (d, J = 8.8 Hz, 1H), 7.11-7.03 (m, 5H), 5.17 (d, J = 1.6 Hz, 1H), 4.18 (d, J = 1.7 Hz, 1H), 2.21 (s, 3H); 13 C NMR (100 MHz, DMSO-d 6 )δ169.4,163.1,139.4,137.7,137.2,134.4,132.1,131.2,129.5,129.3,128.5,128.2,127.4,126.6,123.5,119.9,73.2,61.1,52.1,14.2.
化合物Ic:产率51.2%,白色固体。1H NMR(400MHz,DMSO-d6)δ10.38(s,1H),7.95(d,J=9.1Hz,1H),7.63–7.57(m,2H),7.41–7.35(m,2H),7.22(d,J=8.8Hz,1H),7.16(t,J=8.9Hz,2H),7.06–7.10(m,4H),5.17(d,J=1.6Hz,1H),4.15(d,J=1.7Hz,1H),3.72(q,J=8.9Hz,2H),1.04(t,J=7.1Hz,3H);13C NMR(100MHz,DMSO-d6)δ169.3,163.0,158.6(d,1JFC=240.1Hz),137.7,137.1,135.8,134.3,132.1,130.7,129.5,128.5,128.2,127.4,126.7(d,1JFC=210.8Hz),126.6,121.7(d,3JFC=7.8Hz),115.8(d,2JFC=22.3Hz),61.0,57.7(q,2JFC=27.8Hz),13.2.Compound Ic: yield 51.2%, white solid. 1 H NMR (400MHz, DMSO-d 6 ) δ10.38 (s, 1H), 7.95 (d, J = 9.1Hz, 1H), 7.63–7.57 (m, 2H), 7.41–7.35 (m, 2H), 7.22 (d, J = 8.8Hz, 1H), 7.16 (t, J = 8.9Hz, 2H), 7.06 –7.10(m,4H),5.17(d,J=1.6Hz,1H),4.15(d,J=1.7Hz,1H),3.72(q,J=8.9Hz,2H),1.04(t,J=7.1Hz,3H); 13 C NMR(100MHz,DMSO-d 6 )δ169.3,163.0,158.6(d, 1 J FC =240.1Hz),137.7,137.1,135.8,134.3,132.1,130.7,129.5,128.5,128.2,127.4,126.7(d, 1 J FC =210.8Hz), 126.6,121.7(d, 3 J FC =7.8Hz),115 .8(d, 2 J FC =22.3Hz),61.0,57.7(q, 2 J FC =27.8Hz),13.2.
化合物Id:产率31.4%,白色固体。1H NMR(400MHz,DMSO-d6)δ7.99(d,J=7.7Hz,1H),7.48(d,J=7.5Hz,1H),7.27(s,1H),6.34(s,2H),4.97(d,J=5.7Hz,1H),4.32(d,J=5.7Hz,1H),3.86(dq,J=14.0,7.1Hz,1H),3.61(s,3H),3.58(s,6H),3.08–3.03(m,2H),2.93(dq,J=14.0,7.0Hz,1H),2.42(s,3H),1.06(t,J=7.1Hz,3H),1.00(t,J=7.2Hz,3H);13C NMR(100MHz,DMSO-d6)δ168.3,163.5,152.7,137.5,135.7,133.6,132.1,129.8,127.9,127.6,127.5,106.0,62.2,60.4,56.0,49.9,40.6,33.9,23.8 15.0,13.4.HRMS(ESI)calcd.for C23H29N2O5[M+H]+413.2076,found 413.2071.Compound Id: yield 31.4%, white solid. 1 H NMR (400MHz, DMSO-d 6 ) δ7.99 (d, J = 7.7Hz, 1H), 7.48 (d, J = 7.5Hz, 1H), 7.27 (s, 1H), 6.34 (s, 2H), 4.97 (d, J = 5.7Hz, 1H), 4.32 (d, J = 5.7Hz, 1H), 3.86 (dq, J = 14.0,7.1Hz,1H),3.61(s,3H),3.58(s,6H),3.08–3.03(m,2H),2.93(dq,J=14.0,7.0Hz,1H),2.42(s,3H),1.06(t,J=7.1Hz,3H),1.00(t,J=7.2Hz,3H); 13C NMR (100MHz, DMSO-d 6 ) δ168.3,163.5,152.7,137.5,135.7,133.6,132.1,129.8,127.9,127.6,127.5,106.0,62.2,60.4,56.0,49.9,40.6,33.9,23.8 15.0,13.4.HRMS(ESI)calcd.for C 23 H 29 N 2 O 5 [M+H] + 413.2076,found 413.2071.
化合物Ie:产率35.5%,黄色固体。1H NMR(400MHz,DMSO-d6)δ8.11(t,J=5.6Hz,1H),7.93(dd,J=7.1,2.0Hz,1H),7.44–7.33(m,2H),7.16(dd,J=6.9,1.9Hz,1H),6.41(s,2H),5.03(d,J=1.9Hz,1H),4.00(d,J=1.9Hz,1H),3.93(dq,J=14.1,7.1Hz,1H),3.61(s,6H),3.57(s,3H),3.36–3.31(m,2H),3.28–3.21(m,4H);13C NMR(100MHz,DMSO-d6)δ171.0,163.2,153.2,137.1,136.3,135.1,132.1,130.6,128.8,128.1,127.1,126.78-126.62,104.2,71.1,61.8,60.3,58.4,56.2,51.5,13.1.Compound Ie: yield 35.5%, yellow solid. 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.11 (t, J = 5.6 Hz, 1H), 7.93 (dd, J = 7.1, 2.0 Hz, 1H), 7.44-7.33 (m, 2H), 7.16 (dd, J = 6.9, 1.9 Hz, 1H), 6.41 (s, 2H), 5.03 (d, J = 1.9 Hz, 1H), 4.00 (d, J = 1.9 Hz, 1H), 3.93 (dq, J = 14.1, 7.1 Hz, 1H), 3.61 (s, 6H), 3.57 (s, 3H), 3.36-3.31 (m, 2H), 3.28-3.21 (m, 4H); 13 C NMR (100 MHz, DMSO-d 6 )δ171.0,163.2,153.2,137.1,136.3,135.1,132.1,130.6,128.8,128.1,127.1,126.78-126.62,104.2,71.1,61.8,60.3,58.4,56.2,51.5,13.1.
化合物Ig:产率31.6%,白色固体。1H NMR(400MHz,DMSO-d6)δ10.30(s,1H),7.96(dd,J=7.4,1.7Hz,1H),7.62–7.57(m,4H),7.46–7.39(m,9H),7.31(dd,J=7.3,1.6Hz,1H),7.16(t,J=8.9Hz,2H),,5.13(d,J=1.6Hz,1H),4.14(d,J=1.6Hz,1H),3.94(dq,J=14.1,7.1Hz,1H),2.91(dq,J=14.0,7.0Hz,1H),1.07(t,J=7.1Hz,3H);13C NMR(100MHz,DMSO-d6)δ169.3,162.9,158.6(d,1JFC=240.5Hz),153.2,140.8,137.2,136.5,135.7,134.4,132.2,130.6,129.2,128.6,128.3,127.9,127.6,127.3,121.8(d,3JFC=7.9Hz),115.8(d,2JFC=22.3Hz),104.3,61.2,60.4,56.2,13.1.Compound Ig: yield 31.6%, white solid. 1 H NMR(400MHz,DMSO-d 6 )δ10.30(s,1H),7.96(dd,J=7.4,1.7Hz,1H),7.62–7.57(m,4H),7.46–7.39(m,9H),7.31(dd,J=7.3,1.6Hz,1H),7.16(t,J=8.9Hz,2H),,5.13(d,J=1.6Hz,1H),4.14(d,J=1.6Hz,1H),3.94(dq,J=14.1,7.1Hz,1H),2.91(dq,J=14.0,7.0Hz,1H),1.07(t,J=7.1Hz,3H); 13 C NMR(100MHz,DMSO-d 6 )δ169.3,162.9,158.6(d, 1 J FC =240.5Hz),153.2,140.8,137.2,136.5,135.7,134.4,132.2,130.6,129.2,128.6,128.3,127.9,127.6,127.3,12 1.8 (d, 3 J FC =7.9Hz), 115.8 (d, 2 J FC = 22.3Hz), 104.3, 61.2, 60.4, 56.2, 13.1.
化合物Ih:产率54.6%,黄色固体。1H NMR(400MHz,DMSO-d6)δ10.44(s,1H),8.03(dd,J=7.7,1.5Hz,1H),7.77–7.62(m,4H),7.54–7.48(m,6H),7.44(td,J=7.5,1.4Hz,1H),7.33(dd,J=7.7,1.2Hz,1H),6.31(s,2H),5.15(d,J=5.9Hz,1H),4.59(d,J=5.7Hz,1H),3.87(dq,J=14.1,7.1Hz,1H),2.97(dq,J=13.9,7.0Hz,1H),2.29(q,J=7.0Hz,2H),1.19(t,J=7.0Hz,3H),1.09(t,J=7.0Hz,3H);13C NMR(100MHz,DMSO-d6)δ167.6,163.5,152.7,138.6,137.5,134.9,133.7,133.3,132.2,132.0,131.8,129.8,128.1,128.0,127.9,127.6,127.5,127.3,126.0,121.8,115.7,105.7,62.1,52.4,50.7,14.7,13.5.Compound Ih: Yield 54.6%, yellow solid. 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.44 (s, 1H), 8.03 (dd, J = 7.7, 1.5 Hz, 1H), 7.77-7.62 (m, 4H), 7.54-7.48 (m, 6H), 7.44 (td, J = 7.5, 1.4 Hz, 1H), 7.33 (dd, J = 7.7, 1.2 Hz, 1H), 6.31 (s, 2H), 5.15 (d, J =5.9Hz,1H),4.59(d,J=5.7Hz,1H),3.87(dq,J=14.1,7.1Hz,1H),2.97(dq,J=13.9,7.0Hz,1H),2.29(q,J=7.0Hz,2H),1.19(t,J=7.0Hz,3H),1.09(t,J= 7.0Hz,3H); 13 C NMR (100MHz, DMSO-d 6 ) δ167.6,163.5,152.7,138.6,137.5,134.9,133.7,133.3,132.2,132.0,131.8,129.8,128.1,128.0,127.9,127.6,127.5 ,127.3,126.0,121.8,115.7,105.7,62.1,52.4,50.7,14.7,13.5.
化合物Ii:产率69.5%,白色固体。1H NMR(400MHz,DMSO-d6)δ7.94(t,J=1.8Hz,1H),7.92(d,J=2.5Hz,1H),7.40–7.35(m,2H),7.14(dd,J=6.8,1.9Hz,1H),6.91(d,J=8.7Hz,2H),6.57(d,J=8.8Hz,2H),4.96(d,J=1.8Hz,1H),3.93(dq,J=14.1,7.1Hz,1H),3.85(d,J=1.8Hz,1H),3.13–3.03(m,2H),2.80–2.78(m,7H),1.06–1.00(m,6H);13C NMR(100MHz,DMSO-d6)δ170.3,163.0,150.1,134.9,132.0,130.5,128.8,127.9,127.8,127.3,127.2,112.6,61.3,52.1,40.9,15.1,13.1.Compound Ii: Yield 69.5%, white solid. 1 H NMR (400MHz, DMSO-d 6 ) δ7.94 (t, J = 1.8Hz, 1H), 7.92 (d, J = 2.5Hz, 1H), 7.40–7.35 (m, 2H), 7.14 (dd, J = 6.8, 1.9Hz, 1H), 6.91 (d, J = 8.7Hz, 2H), 6.57 (d, J = 8.8 13 C NMR(1 00MHz, DMSO-d 6 )δ170.3,163.0,150.1,134.9,132.0,130.5,128.8,127.9,127.8,127.3,127.2,112.6,61.3,52.1,40.9,15.1,13.1.
化合物Ij:产率69.5%,橙黄色固体。1H NMR(400MHz,DMSO-d6)δ8.10(t,J=5.5Hz,1H),7.93(dd,J=7.0,2.2Hz,1H),7.41–7.32(m,2H),7.13(dd,J=6.9,2.0Hz,1H),6.92–6.87(m,3H),4.95(d,J=1.9Hz,1H),3.94–3.89(m,2H),3.34–3.30(m,2H),3.26–3.19(m,5H),2.82–2.77(m,7H),1.04(t,J=7.1Hz,3H);13C NMR(100MHz,DMSO-d6)δ170.7,163.0,150.1,134.9,131.9,130.6,128.7,127.9,127.6,127.3,127.3,112.6,71.0,61.3,58.4,51.9,40.9,40.5,39.2,13.1.Compound Ij: Yield 69.5%, orange-yellow solid. 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.10 (t, J = 5.5 Hz, 1H), 7.93 (dd, J = 7.0, 2.2 Hz, 1H), 7.41-7.32 (m, 2H), 7.13 (dd, J = 6.9, 2.0 Hz, 1H), 6.92-6.87 (m, 3H), 4.95 (d, J = 1.9 Hz, 1H), 3.94-3.89 (m, 2H), 3.34-3.30 (m, 2H), 3.26-3.19 (m, 5H), 2.82-2.77 (m, 7H), 1.04 (t, J = 7.1 Hz, 3H); 13 C NMR (100 MHz, DMSO-d 6 )δ170.7,163.0,150.1,134.9,131.9,130.6,128.7,127.9,127.6,127.3,127.3,112.6,71.0,61.3,58.4,51.9,40.9,40.5,39.2,13.1.
化合物Ik:产率64.2%,白色固体。1H NMR(400MHz,DMSO-d6)δ10.29(s,1H),7.95(d,J=5.3Hz,1H),7.58(d,J=5.3Hz,1H),7.43–7.35(m,2H),7.31(t,J=7.9Hz,2H),7.24(d,J=6.7Hz,1H),7.05(t,J=7.3Hz,1H),6.99–6.85(m,3H),5.05(d,J=1.7Hz,1H),4.14(d,J=1.6Hz,1H),3.93(dq,J=14.1,7.0Hz,1H),2.88–2.81(m,7H),1.04(t,J=7.1Hz,3H);13C NMR(100MHz,DMSO-d6)δ169.6,162.9,150.2,139.4,134.7,132.0,130.8,129.2,128.5,128.1,127.7,127.4,123.9,119.9,112.6,61.0,52.4,41.0,40.5,13.1.Compound Ik: yield 64.2%, white solid. 1 H NMR (400MHz, DMSO-d 6 ) δ10.29 (s, 1H), 7.95 (d, J = 5.3Hz, 1H), 7.58 (d, J = 5.3Hz, 1H), 7.43–7.35 (m, 2H), 7.31 (t, J = 7.9Hz, 2H), 7.24 (d, J = 6.7Hz, 1H), 7.05 (t,J=7.3Hz,1H),6.99–6.85(m,3H),5.05(d,J=1.7Hz,1H),4.14(d,J=1.6Hz,1H),3.93(dq,J=14.1,7.0Hz,1H),2.88–2.81(m,7H),1.04(t,J=7.1Hz,3H) ; 13C NMR (100MHz, DMSO-d 6 ) δ169.6,162.9,150.2,139.4,134.7,132.0,130.8,129.2,128.5,128.1,127.7,127.4,123.9,119.9,112.6,61.0,52.4,41.0,40 .5,13.1.
化合物Il:产率35.3%,黄色固体。1H NMR(400MHz,DMSO-d6)δ10.36(s,1H),7.94(dd,J=7.1,2.0Hz,1H),7.62–7.55(m,2H),7.43–7.35(m,2H),7.23(dd,J=6.9,1.9Hz,1H),7.15(t,J=8.9Hz,2H),6.98(d,J=8.8Hz,2H),5.05(d,J=1.8Hz,1H),4.11(d,J=1.8Hz,1H),3.93(dq J=13.9,7.0Hz,1H),2.81(s,3H),1.03(t,J=7.1Hz,3H);13C NMR(100MHz,DMSO-d6)δ169.0,162.4,157.6(d,1JFC=156.5Hz),149.7,135.3,134.1,131.6,130.3,128.1,127.6,127.2,127.7(q,1JFC=226.7Hz),126.9,122.4,122.3,121.2(d,3JFC=7.9Hz),115.3(d,2JFC=22.2Hz),112.2,60.5,51.9,27.2,12.7.Compound Il: yield 35.3%, yellow solid. 1 H NMR (400MHz, DMSO-d 6 ) δ10.36 (s, 1H), 7.94 (dd, J=7.1, 2.0Hz, 1H), 7.62–7.55 (m, 2H), 7.43–7.35 (m, 2H), 7.23 (dd, J=6.9, 1.9Hz, 1H), 7.15 (t, J=8.9Hz, 2H), 6.98 (d, J = 8.8Hz, 2H), 5.05 (d, J = 1.8Hz, 1H), 4.11 (d, J = 1.8Hz, 1H), 3.93 (dq J = 13.9, 7.0Hz, 1H), 2.81 (s, 3H), 1.03 (t, J = 7.1Hz, 3H); 13 C NMR (100MHz, DMSO -d 6 )δ169.0,162.4,157.6(d, 1 J FC =156.5Hz),149.7,135.3,134.1,131.6,130.3,128.1,127.6,127.2,127.7(q, 1 J FC =226.7Hz),126.9,122.4,122 .3,121.2(d, 3 J FC =7.9Hz),115.3(d, 2 J FC =22.2Hz),112.2,60.5,51.9,27.2,12.7.
化合物Im:产率57.4%,白色固体。1H NMR(400MHz,DMSO-d6)δ10.46(s,1H),8.02(d,J=6.1Hz,1H),7.51–7.48(m,5H),7.42(t,J=7.1Hz,1H),7.32(d,J=7.7Hz,1H),6.77(d,J=8.8Hz,2H),6.48(d,J=8.9Hz,2H),5.05(d,J=6.0Hz,1H),4.61(d,J=6.0Hz,1H),3.82(dq,J=13.6,7.0Hz,1H),2.91(dq,J=13.6,7.0Hz,1H),2.80(s,6H),1.07(t,J=7.1Hz,3H);13C NMR(100MHz,DMSO-d6)δ167.6,163.1,150.4,138.6,135.1,132.1,132.0,129.8,128.9,128.3,127.7,127.6,124.6,122.0,115.6,112.1,61.7,50.6,40.6,40.4,13.6.Compound Im: yield 57.4%, white solid. 1 H NMR (400MHz, DMSO-d 6 ) δ10.46 (s, 1H), 8.02 (d, J = 6.1Hz, 1H), 7.51–7.48 (m, 5H), 7.42 (t, J = 7.1Hz, 1H), 7.32 (d, J = 7.7Hz, 1H), 6.77 (d, J = 8.8Hz, 2H), 6.48 (d,J=8.9Hz,2H),5.05(d,J=6.0Hz,1H),4.61(d,J=6.0Hz,1H),3.82(dq,J=13.6,7.0Hz,1H),2.91(dq,J=13.6,7.0Hz,1H),2.80(s,6H),1.07(t,J=7.1Hz, 3H); 13C NMR(100MHz,DMSO-d 6 )δ167.6,163.1,150.4,138.6,135.1,132.1,132.0,129.8,128.9,128.3,127.7,127.6,124.6,122.0,115.6,112.1,61.7,50.6,4 0.6,40.4,13.6.
化合物In:产率64.6%,黄色固体。1H NMR(600MHz,Chloroform-d)δ8.23(d,J=7.4Hz,1H),8.07(d,J=8.5Hz,2H),7.50(t,J=7.4Hz,1H),7.46(t,J=6.8Hz,1H),7.28(d,J=8.5Hz,2H),7.06(s,1H),5.64(d,J=1.7Hz,1H),4.18(dq,J=13.7,7.0Hz,1H),3.74(d,J=1.8Hz,1H),3.23–3.17(m,2H),2.88(dq,J=14.0,6.9Hz,1H),1.18(t,J=7.0Hz,3H),0.99(t,J=7.1Hz,3H);13C NMR(150MHz,Chloroform-d)δ169.2,162.94,147.5,147.0,132.9,131.7,129.6,129.5,128.9,127.1,124.0,61.3,53.5,41.8,35.2,14.5,12.9.Compound In: yield 64.6%, yellow solid. 1 H NMR (600MHz, Chloroform-d) δ8.23(d,J=7.4Hz,1H),8.07(d,J=8.5Hz,2H),7.50(t,J=7.4Hz,1H),7.46(t,J=6.8Hz,1H),7.28(d,J=8.5Hz,2H),7.06(s,1H),5 .64(d,J=1.7Hz,1H),4.18(dq,J=13.7,7.0Hz,1H),3.74(d,J=1.8Hz,1H),3.23–3.17(m,2H),2.88(dq,J=14.0,6.9Hz,1H),1.18(t,J=7.0Hz,3H),0.99( t,J=7.1Hz,3H); 13 C NMR (150MHz, Chloroform-d) δ 169.2, 162.94, 147.5, 147.0, 132.9, 131.7, 129.6, 129.5, 128.9, 127.1, 124.0, 61.3, 53.5, 41.8, 35.2, 14.5, 12.9.
化合物Io:产率57.1%,黄色固体。1H NMR(600MHz,DMSO-d6)δ10.45(s,1H),8.17(d,J=8.5Hz,2H),7.96(d,J=3.8Hz,1H),7.60(dd,J=8.5,4.8Hz,2H),7.51(d,J=8.5Hz,2H),7.42–7.37(m,2H),7.24(d,J=3.3Hz,1H),7.17(t,J=8.7Hz,2H),5.44(d,J=1.6Hz,1H),4.22(d,J=1.7Hz,1H),3.98(dq,J=13.8,6.8Hz,1H),3.68(s.3H),2.92(dq,J=13.7,6.5Hz,1H),1.05(t,J=6.9Hz,3H);13CNMR(150MHz,DMSO-d6)δ168.8,163.1,158.6(d,1JFC=241.7Hz),148.5,147.4,135.7,133.8,132.4,130.5,128.5,128.1,127.6(d,1JFC=222.7Hz),124.2,121.7(d,3JFC=7.7Hz),115.9(d,2JFC=22.3Hz),60.8,52.5,51.5,41.4,13.1.Compound Io: Yield 57.1%, yellow solid. 1 H NMR (600 MHz, DMSO-d 6 )δ10.45(s,1H),8.17(d,J=8.5Hz,2H),7.96(d,J=3.8Hz,1H),7.60(dd,J=8.5,4.8Hz,2H),7.51(d,J=8.5Hz,2H),7.42–7.37(m,2H),7.24(d,J=3.3Hz,1H ),7.17(t,J=8.7Hz,2H),5.44(d,J=1.6Hz,1H),4.22(d,J=1.7Hz,1H),3.98(dq,J=13.8,6.8Hz,1H),3.68(s.3H),2.92(dq,J=13.7,6.5Hz,1H),1.05(t ,J=6.9Hz,3H); 13 CNMR(150MHz,DMSO-d 6 )δ168.8,163.1,158.6(d, 1 J FC =241.7Hz),148.5,147.4,135.7,133.8,132.4,130.5,128.5,128.1,127.6(d, 1 J FC =222.7Hz), 124.2, 121.7 (d, 3 J FC = 7.7Hz), 115.9 (d, 2 J FC = 22.3Hz), 60.8, 52.5, 51.5, 41.4, 13.1.
化合物Ip:产率22.1%,黄色固体。1H NMR(400MHz,Chloroform-d)δ8.34(s,1H),7.57(t,J=4.3Hz,2H),7.26–7.23(m,3H),7.06(d,J=7.4Hz,2H),6.98–6.95(m,3H),6.80(t,J=54.9Hz,1H)6.77(d,J=3.3Hz,1H),5.67(d,J=1.7Hz,1H),4.90(dq,J=18.6,9.2Hz,1H),4.01(d,J=1.8Hz,1H),3.37(dq,J=16.7,8.3Hz,1H),2.27(s,3H);13C NMR(100MHz,Chloroform-d)δ167.8,164.2,160,0(d,1JFC=245.6Hz)138.2,134.6,133.8,132.6,132.4,129.7,129.7,129.5,129.3,128.4,125.9,124.5(q,1JFC=275.9Hz),122.7(d,3JFC=8.1Hz),115.7(d,2JFC=22.7Hz),115.1(d,1JFC=142.7Hz),63.3,54.6,51.0,46.7(q,2JFC=34.2Hz),21.0.Compound Ip: yield 22.1%, yellow solid. 1 H NMR (400 MHz, Chloroform-d) δ8.34 (s, 1H), 7.57 (t, J = 4.3 Hz, 2H), 7.26-7.23 (m, 3H), 7.06 (d, J = 7.4 Hz, 2H), 6.98-6.95 (m, 3H), 6.80 (t, J = 54.9 Hz, 1H) 6.77 (d, J = 3.3 Hz, 1H), 5.67 (d, J = 1.7 Hz, 1H), 4.90 (dq, J = 18.6, 9.2 Hz, 1H), 4.01 (d, J = 1.8 Hz, 1H), 3.37 (dq, J = 16.7, 8.3 Hz, 1H), 2.27 (s, 3H); 13 C NMR(100MHz,Chloroform-d)δ167.8,164.2,160,0(d, 1 J FC =245.6Hz)138.2,134.6,133.8,132.6,132.4,129.7,129.7,129.5,129.3,128.4,125.9,124.5(q , 1 J FC =275.9Hz), 122.7 (d, 3 J FC = 8.1Hz), 115.7 (d, 2 J FC = 22.7Hz), 115.1 (d, 1 J FC = 142.7Hz), 63.3, 54.6, 51.0, 46.7 (q, 2 J FC = 34.2Hz), 21.0.
化合物Iq:产率54.8%,绿色固体。1H NMR(600MHz,Chloroform-d)δ8.27(d,J=6.2Hz,1H),8.09(d,J=8.6Hz,2H),7.57–7.50(m,2H),7.26(d,J=8.3Hz,2H),7.10(d,J=5.0Hz,1H),5.78(d,J=1.5Hz,1H),4.64(dq,J=15.1,8.9Hz,1H),3.81(d,J=1.6Hz,1H),3.70(dq,J=17.5,8.8Hz,1H),3.27–3.17(m,2H),1.33(s,9H),1.00(t,J=7.1Hz,3H);13CNMR(150MHz,Chloroform-d)δ168.5,164.0,147.7,145.6,133.9,132.1,129.7,129.5,129.1,128.1,127.0,124.1,124.0(q,1JFC=280.4Hz),63.2,53.7,47.3(q,2JFC=34.7Hz),35.3,34.2,31.3,14.4.Compound Iq: Yield 54.8%, green solid. 1 H NMR (600 MHz, Chloroform-d) δ8.27 (d, J = 6.2 Hz, 1H), 8.09 (d, J = 8.6 Hz, 2H), 7.57-7.50 (m, 2H), 7.26 (d, J = 8.3 Hz, 2H), 7.10 (d, J = 5.0 Hz, 1H), 5.78 (d, J = 1.5 Hz, 1H), 4.64 (dq, J = 15.1, 8.9 Hz, 1H), 3.81 (d, J = 1.6 Hz, 1H), 3.70 (dq, J = 17.5, 8.8 Hz, 1H), 3.27-3.17 (m, 2H), 1.33 (s, 9H), 1.00 (t, J = 7.1 Hz, 3H); 13 CNMR(150MHz,Chloroform-d)δ168.5,164.0,147.7,145.6,133.9,132.1,129.7,129.5,129.1,128.1,127.0,124.1,124.0(q, 1 J FC =280.4Hz),63.2,53.7,4 7.3(q, 2 J FC =34.7Hz),35.3,34.2,31.3,14.4.
化合物Ir:产率68.5%,白色固体。1H NMR(400MHz,DMSO-d6)δ10.55(s,1H),8.18(d,J=8.8Hz,2H),8.00(dd,J=7.1,2.0Hz,1H),7.62–7.55(m,2H),7.50(d,J=8.8Hz,2H),7.48–7.41(m,2H),7.25(dd,J=7.0,1.7Hz,1H),7.17(t,J=8.9Hz,2H),5.58(d,J=1.7Hz,1H),4.62(dq,J=15.2,9.4Hz,1H),4.30(d,J=1.8Hz,1H),4.09(dq,J=15.3,9.5Hz,1H),4.05(q,J=7.5Hz,2H),1.35(t,J=7.5Hz,3H);13C NMR(100MHz,DMSO-d6)δ168.2,164.6,158.6(d,1JFC=240.3Hz),147.5,147.3,135.6,134.9,134.2,133.3,129.5,128.8,128.0,128.0,125.3(q,1JFC=281.6Hz),124.1,121.8(d,3JFC=7.8Hz),115.9(d,2JFC=22.3Hz),64.6,63.1,51.7,47.1,14.8(q,2JFC=33.5Hz).Compound Ir: Yield 68.5%, white solid. 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.55 (s, 1H), 8.18 (d, J = 8.8 Hz, 2H), 8.00 (dd, J = 7.1, 2.0 Hz, 1H), 7.62-7.55 (m, 2H), 7.50 (d, J = 8.8 Hz, 2H), 7.48-7.41 (m, 2H), 7.25 (dd, J = 7.0, 1.7 Hz, 1H), 7.17 (t ,J=8.9Hz,2H),5.58(d,J=1.7Hz,1H),4.62(dq,J=15.2,9.4Hz,1H),4.30(d,J=1.8Hz,1H),4.09(dq,J=15.3,9.5Hz,1H),4.05(q,J=7.5Hz,2H),1.35(t, J=7.5Hz,3H); 13 C NMR (100MHz, DMSO-d 6 ) δ 168.2, 164.6, 158.6 (d, 1 J FC = 240.3Hz), 147.5, 147.3, 135.6, 134.9, 134.2, 133.3, 129.5, 128.8, 128.0, 128.0, 125.3 (q, 1 J FC = 281.6Hz), 124.1, 121.8 (d, 3 J FC = 7.8Hz), 115.9 (d, 2 J FC = 22.3Hz), 64.6, 63.1, 51.7, 47.1, 14.8 (q, 2 J FC = 33.5Hz).
化合物Is:产率78.5%,白色固体。1H NMR(400MHz,Chloroform-d)δ8.28(dd,J=7.2,1.9Hz,1H),8.08(d,J=8.7Hz,2H),7.99(dd,J=4.9,1.4Hz,1H),7.55–7.48(m,2H),7.30(d,J=8.7Hz,2H),7.13(s,1H),6.74(dd,J=7.7,4.9Hz,1H),5.96(s,2H),5.66(d,J=1.5Hz,1H),4.08(dq,J=14.3,7.2Hz,1H),3.93(d,J=1.5Hz,1H),3.03(dq,J=14.3,7.2Hz,1H),1.12(t,J=7.2Hz,3H);13C NMR(100MHz,DMSO-d6)δ169.7,163.1,154.2,148.5,147.4,146.5,137.6,133.3,132.3,130.6,128.7,128.5,128.2,127.5,124.2,116.2,114.4,112.2,110.8,101.2,61.7,49.4,41.9,13.1.Compound Is: Yield 78.5%, white solid. NMR(400MHz,Chloroform-d)δ8.28(dd,J=7.2,1.9Hz,1H),8.08(d,J=8.7Hz,2H),7.99(dd,J=4.9,1.4Hz,1H),7.55–7.48(m,2H),7.30(d,J=8.7Hz,2H),7.13(s,1H) ,6.74(dd,J=7.7,4.9Hz,1H),5.96(s,2H),5.66(d,J=1.5Hz,1H),4.08(dq,J=14.3,7.2Hz,1H),3.93(d,J=1.5Hz,1H),3.03(dq,J=14.3,7.2Hz,1H),1.1 2(t,J=7.2Hz,3H); 13 C NMR (100MHz, DMSO-d 6 ) δ169.7,163.1,154.2,148.5,147.4,146.5,137.6,133.3,132.3,130.6,128.7,128.5,128.2,127.5,124.2,116.2,114.4 ,112.2,110.8,101.2,61.7,49.4,41.9,13.1.
化合物It:产率68.7%,黄色油状。1H NMR(400MHz,Chloroform-d)δ8.25(dd,J=5.5,3.7Hz,1H),7.97(dd,J=4.9,1.5Hz,1H),7.67–7.57(m,1H),7.52–7.45(m,2H),7.27–7.24(m,1H),7.14(s,1H),7.01–6.95(m,4H)6.71(dd,J=7.7,4.9Hz,1H),,5.43(d,J=1.4Hz,1H),4.05(dq,J=14.3,7.2Hz,1H),3.92(d,J=1.5Hz,1H),3.74(s,3H),3.65(s,6H),3.02(dq,J=14.3,7.2Hz,1H),2.70(t,J=7.2Hz,1H),1.74(t,J=7.2Hz,1H),1.13(t,J=7.2Hz,3H);13C NMR(100MHz,Chloroform-d)δ168.6,163.0,153.3,152.1,145.9,137.0,134.7,132.6,131.6,130.2,129.3,129.2,128.4,116.8,115.7,103.3,61.2,60.7,56.0,52.2,41.7,29.8,22.7,12.8.Compound It: Yield 68.7%, yellow oil. 1 H NMR (400 MHz, Chloroform-d) δ8.25 (dd, J = 5.5, 3.7 Hz, 1H), 7.97 (dd, J = 4.9, 1.5 Hz, 1H), 7.67-7.57 (m, 1H), 7.52-7.45 (m, 2H), 7.27-7.24 (m, 1H), 7.14 (s, 1H), 7.01-6.95 (m, 4H) 6.71 (dd, J = 7.7, 4.9 Hz, 1H ),,5.43(d,J=1.4Hz,1H),4.05(dq,J=14.3,7.2Hz,1H),3.92(d,J=1.5Hz,1H),3.74(s,3H),3.65(s,6H),3.02(dq,J=14.3,7.2Hz,1H),2.70(t,J=7.2Hz, 1H),1.74(t,J=7.2Hz,1H),1.13(t,J=7.2Hz,3H); 13 C NMR (100MHz, Chloroform-d) δ168.6,163.0,153.3,152.1,145.9,137.0,134.7,132.6,131.6,130.2,129.3,129.2,128.4,116.8,115.7,103.3,61.2, 60.7,56.0,52.2,41.7,29.8,22.7,12.8.
化合物Iu:产率64.8%,黄色固体。1H NMR(400MHz,DMSO-d6)δ10.47(d,J=1.7Hz,1H),8.58(d,J=6.7Hz,2H),8.03(dd,J=4.8,1.4Hz,1H),7.99(dd,J=7.3,1.6Hz,1H),7.72(dd,J=7.7,1.4Hz,1H),7.53–7.39(m,4H),7.23(d,J=6.0Hz,1H),7.17(t,J=6.7Hz,1H),6.81(dd,J=7.7,4.9Hz,1H),5.55(d,J=1.6Hz,1H),4.52(dq,J=14.3,7.2Hz,1H),4.33–4.21(m,2H);13C NMR(100MHz,DMSO-d6)δ169.3,157.4,154.1,147.4,149.3,146.3,137.7,133.8,133.2,129.6,128.9,128.8,128.0,128.0,126.6(q,1JFC=204.5Hz),121.8,116.3,114.5,64.0,49.6,48.0(q,2JFC=33.8Hz).Compound Iu: yield 64.8%, yellow solid. 1 H NMR (400MHz, DMSO-d 6 ) δ10.47(d,J=1.7Hz,1H),8.58(d,J=6.7Hz,2H),8.03(dd,J=4.8,1.4Hz,1H),7.99(dd,J=7.3,1.6Hz,1H),7.72(dd,J=7.7,1.4Hz,1H),7 .53–7.39(m,4H),7.23(d,J=6.0Hz,1H),7.17(t,J=6.7Hz,1H),6.81(dd,J=7 .7,4.9Hz,1H),5.55(d,J=1.6Hz,1H),4.52(dq,J=14.3,7.2Hz,1H),4.33–4.2 1(m,2H); 13 C NMR (100MHz, DMSO-d 6 ) δ 169.3, 157.4, 154.1, 147.4, 149.3, 146.3, 137.7, 133.8, 133.2, 129.6, 128.9, 128.8, 128.0, 128.0, 126.6 (q, 1 J FC = 204. 5Hz),121.8,116.3,114.5,64.0,49.6,48.0(q, 2 J FC =33.8Hz).
实施例2,目标化合物I的抗植物病原真菌活性的实验方法及结果。Example 2, experimental method and results of the anti-plant pathogenic fungi activity of target compound I.
本发明利用菌丝生长速率法测试了目标化合物Ia--Iu对苹果炭疽病(Colletotrichum gloeosporioides)、小麦赤霉病菌(Fusarium graminearum)、番茄早疫病菌(Alternaria solani)、苹果轮纹病菌(Physalospora piricola)、玉米纹枯病菌(RhizoctoniasolanikOhn)和梨黑斑病菌(Alternaria alternata)等6种常见农作物致病菌的离体活性,以百菌清(Chlorothalonil)和多菌灵(Carbendazim)作为对照药。将化合物溶于DMSO中,配成10mg/mL的溶液,用0.5%的吐温20稀释成浓度为1mg/mL的测试液。取0.75mL上述测试液加入到45mL离心管中,再趁热加入PDA培养基定容至15mL,混合均匀后倒入培养皿,冷却凝固后接入供试菌种,将等量不含目标化合物的测试液作为空白对照。每组平行3次,在25±1℃下倒置培养,统计结果时取平均值。使用十字交叉法测量菌落直径。抗植物病原真菌测试结果见表2。The present invention uses the hyphae growth rate method to test the in vitro activity of the target compound Ia--Iu against 6 common crop pathogens, including apple anthracnose (Colletotrichum gloeosporioides), wheat fusarium (Fusarium graminearum), tomato early blight (Alternaria solani), apple ring rot fungus (Physalospora piricola), corn sheath blight fungus (RhizoctoniasolanikOhn ) and pear black spot fungus (Alternaria alternata), and uses chlorothalonil (Chlorothalonil) and carbendazim (Carbendazim) as control drugs. The compound is dissolved in DMSO to prepare a 10 mg/mL solution, and diluted with 0.5% Tween 20 to a test solution with a concentration of 1 mg/mL. Take 0.75mL of the above test solution and add it to a 45mL centrifuge tube. Then add PDA medium to 15mL while it is hot. Pour it into a culture dish after mixing evenly. After cooling and solidification, inoculate the test bacteria. Use an equal amount of test solution without the target compound as a blank control. Each group was cultured in an inverted manner at 25±1℃ for 3 times in parallel. The average value was taken when the results were statistically analyzed. The colony diameter was measured using the cross method. The results of the anti-plant pathogenic fungi test are shown in Table 2.
表2目标化合物Ia--Iu的抗植物病原真菌活性实验数据。Table 2 Experimental data of the anti-plant pathogenic fungi activity of target compounds Ia--Iu.
目标化合物对玉米纹枯病菌最敏感,有14个化合物抑制率高于50.00%,其中化合物Ih抑制率最高为80.03%,高于阳性对照百菌清(77.97%),低于多菌灵。总体来说,本发明所述的二氢异喹啉酮类化合物具有广谱的抗植物病原真菌活性,是一种具有应用前景的杀菌剂候选药物分子。The target compounds are most sensitive to corn sheath blight, with 14 compounds having inhibition rates higher than 50.00%, of which compound Ih has the highest inhibition rate of 80.03%, which is higher than the positive control thiophanate-methyl (77.97%) and lower than carbendazim. In general, the dihydroisoquinolinone compounds described in the present invention have a broad spectrum of anti-plant pathogenic fungi activity and are a fungicide candidate drug molecule with application prospects.
以上实施例仅用以说明本发明的技术方案,而非对其限制;尽管参照前述实施例对本发明进行了详细的说明,本领域的普通技术人员应当理解:其依然可以对前述各实施例所记载的技术方案进行修改,或者对其中部分技术特征进行等同替换;而这些修改或者替换,并不使相应技术方案的本质脱离本发明各实施例技术方案的本质和范围。The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the essence and scope of the technical solutions of the embodiments of the present invention.
Claims (6)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202410836936.1A CN118754852A (en) | 2024-06-26 | 2024-06-26 | Novel dihydroisoquinolinone compounds and their use in preparing anti-plant pathogenic fungicides |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202410836936.1A CN118754852A (en) | 2024-06-26 | 2024-06-26 | Novel dihydroisoquinolinone compounds and their use in preparing anti-plant pathogenic fungicides |
Publications (1)
Publication Number | Publication Date |
---|---|
CN118754852A true CN118754852A (en) | 2024-10-11 |
Family
ID=92942882
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202410836936.1A Pending CN118754852A (en) | 2024-06-26 | 2024-06-26 | Novel dihydroisoquinolinone compounds and their use in preparing anti-plant pathogenic fungicides |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN118754852A (en) |
-
2024
- 2024-06-26 CN CN202410836936.1A patent/CN118754852A/en active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA3015449C (en) | Microbiocidal quinoline (thio)carboxamide derivatives | |
Thomas et al. | New quinolin-4-yl-1, 2, 3-triazoles carrying amides, sulphonamides and amidopiperazines as potential antitubercular agents | |
DE69913364T2 (en) | SUBSTITUTED 3-CYANOCHINOLINE AS A PROTEIN TYROSINE KINASE INHIBITOR | |
US6593342B1 (en) | Pharmaceutical compositions comprising 2-quinolones | |
EP3459951A1 (en) | Beta-carboline, dihydro-beta-carboline and tetrahydro-beta-carboline alkaloid derivatives, method for preparing the same and use in aspects of preventing and treating plant viruses, as fungicides and insecticides | |
JPS6393765A (en) | Substituted phenylsulfonamides | |
CN101580477A (en) | Dehydroabietylamine derivatives and application thereof in bactericidal and antineoplastic medicaments | |
Indumathi et al. | L-Proline anchored multicomponent synthesis of novel pyrido [2, 3-a] carbazoles; investigation of in vitro antimicrobial, antioxidant, cytotoxicity and structure activity relationship studies | |
DE3617183A1 (en) | SUBSTITUTED BENZYL ETHERS | |
WO2015135360A1 (en) | Gossypol aromatic amine schiff base derivative and preparation method and plant virus resistant use thereof | |
CN103787976B (en) | 1-aryl-3-aryl-1H-pyrazoles-5-first hydroximic acid derivative and application thereof | |
Chen et al. | Design, synthesis and mechanism study of novel natural-derived isoquinoline derivatives as antifungal agents | |
CN106349223B (en) | The preparation method and application of the pyrazoles oxime ether compound of the sulfide based structural containing pyrimidine | |
WO2017125952A1 (en) | N-((1-phenyl-9h-pyrido[3,4-b]indol-3-yl)methyl)cinnamamides as anticancer agents and preparation thereof | |
CN118754852A (en) | Novel dihydroisoquinolinone compounds and their use in preparing anti-plant pathogenic fungicides | |
US6645983B1 (en) | Pharmaceutical compositions comprising 4-quinolones for treating cancers | |
Mandhane et al. | Synthesis, characterization and antimicrobial screening of substituted quiazolinones derivatives | |
CN103435622B (en) | A kind of spiro indole diketopiperazine Alkaloid and synthetic method thereof and application | |
CN108864089B (en) | Indolopyridone drug molecule and preparation method and application thereof | |
CN107200731B (en) | A kind of thiazole ring-containing pyridone derivative and its preparation method and application | |
Rao et al. | Design, Synthesis, and Bioactivity of Eighteen Novel 2H‐1, 4‐Benzoxazin‐3 (4H)‐one Containing a Propanolamine Moiety | |
CN106117180A (en) | A kind of substituted pyridine connection pyrazoles bishydrazide compounds and its preparation method and application | |
CN116210706B (en) | Application of alkaloid polyaurine B derivatives in resisting plant viruses and pathogens | |
Bouria et al. | Synthesis, characterization of new α‐quinolin‐3‐yl‐α‐(aminoamides, aminoesters) and bi‐heterocyclic aromatic systems from gem‐dicyanoepoxides and their pharmacological activity as antioxidant and antifungal agents | |
CN111349094B (en) | 6H-imidazo [4,5,1-ij ] quinolone and synthesis method and application thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |