CN114621160A - 一种胡椒碱肟酯类衍生物、制备及应用 - Google Patents
一种胡椒碱肟酯类衍生物、制备及应用 Download PDFInfo
- Publication number
- CN114621160A CN114621160A CN202210320605.3A CN202210320605A CN114621160A CN 114621160 A CN114621160 A CN 114621160A CN 202210320605 A CN202210320605 A CN 202210320605A CN 114621160 A CN114621160 A CN 114621160A
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- CN
- China
- Prior art keywords
- dioxymethylene
- acid
- group
- piperine
- dioxymethylene group
- 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.)
- Granted
Links
- -1 Piperine oxime ester Chemical class 0.000 title claims abstract description 74
- WVWHRXVVAYXKDE-UHFFFAOYSA-N piperine Natural products O=C(C=CC=Cc1ccc2OCOc2c1)C3CCCCN3 WVWHRXVVAYXKDE-UHFFFAOYSA-N 0.000 title claims abstract description 58
- 229940075559 piperine Drugs 0.000 title claims abstract description 53
- 235000019100 piperine Nutrition 0.000 title claims abstract description 53
- 238000002360 preparation method Methods 0.000 title claims description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 70
- MXXWOMGUGJBKIW-YPCIICBESA-N piperine Chemical compound C=1C=C2OCOC2=CC=1/C=C/C=C/C(=O)N1CCCCC1 MXXWOMGUGJBKIW-YPCIICBESA-N 0.000 claims abstract description 25
- 125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 claims abstract description 21
- 239000000460 chlorine Substances 0.000 claims abstract description 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 13
- 230000000895 acaricidal effect Effects 0.000 claims abstract description 13
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 10
- 239000001257 hydrogen Substances 0.000 claims abstract description 10
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 10
- 239000000642 acaricide Substances 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- 239000002917 insecticide Substances 0.000 claims abstract description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 5
- 239000000543 intermediate Substances 0.000 claims description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 12
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 12
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 10
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 claims description 9
- 229930016911 cinnamic acid Natural products 0.000 claims description 9
- 235000013985 cinnamic acid Nutrition 0.000 claims description 9
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- LULAYUGMBFYYEX-UHFFFAOYSA-N 3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 claims description 6
- XHQZJYCNDZAGLW-UHFFFAOYSA-N 3-methoxybenzoic acid Chemical compound COC1=CC=CC(C(O)=O)=C1 XHQZJYCNDZAGLW-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 6
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 claims description 6
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims description 6
- 150000002923 oximes Chemical class 0.000 claims description 6
- LPNBBFKOUUSUDB-UHFFFAOYSA-N p-toluic acid Chemical compound CC1=CC=C(C(O)=O)C=C1 LPNBBFKOUUSUDB-UHFFFAOYSA-N 0.000 claims description 6
- SZHOJFHSIKHZHA-UHFFFAOYSA-N tridecanoic acid Chemical compound CCCCCCCCCCCCC(O)=O SZHOJFHSIKHZHA-UHFFFAOYSA-N 0.000 claims description 6
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 4
- RHBGITBPARBDPH-UHFFFAOYSA-N (2E,4E)-5-(3,4-methylenedioxyphenyl)-2,4-pentadienoic acid Natural products OC(=O)C=CC=CC1=CC=C2OCOC2=C1 RHBGITBPARBDPH-UHFFFAOYSA-N 0.000 claims description 3
- XFRGOISOCUABHY-ZPUQHVIOSA-N (2e,4e)-5-(4-chlorophenyl)penta-2,4-dienoic acid Chemical compound OC(=O)\C=C\C=C\C1=CC=C(Cl)C=C1 XFRGOISOCUABHY-ZPUQHVIOSA-N 0.000 claims description 3
- FTSVYRXMAOYUTQ-ZUVMSYQZSA-N (2e,4e)-5-(4-methylphenyl)penta-2,4-dienoic acid Chemical compound CC1=CC=C(\C=C\C=C\C(O)=O)C=C1 FTSVYRXMAOYUTQ-ZUVMSYQZSA-N 0.000 claims description 3
- FEIQOMCWGDNMHM-KBXRYBNXSA-N (2e,4e)-5-phenylpenta-2,4-dienoic acid Chemical compound OC(=O)\C=C\C=C\C1=CC=CC=C1 FEIQOMCWGDNMHM-KBXRYBNXSA-N 0.000 claims description 3
- AFDXODALSZRGIH-QPJJXVBHSA-N (E)-3-(4-methoxyphenyl)prop-2-enoic acid Chemical compound COC1=CC=C(\C=C\C(O)=O)C=C1 AFDXODALSZRGIH-QPJJXVBHSA-N 0.000 claims description 3
- RHBGITBPARBDPH-ZPUQHVIOSA-N (E,E)-piperic acid Chemical compound OC(=O)\C=C\C=C\C1=CC=C2OCOC2=C1 RHBGITBPARBDPH-ZPUQHVIOSA-N 0.000 claims description 3
- IKCLCGXPQILATA-UHFFFAOYSA-N 2-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1Cl IKCLCGXPQILATA-UHFFFAOYSA-N 0.000 claims description 3
- ISMMYAZSUSYVQG-ZZXKWVIFSA-N 4-Fluorocinnamic acid Chemical compound OC(=O)\C=C\C1=CC=C(F)C=C1 ISMMYAZSUSYVQG-ZZXKWVIFSA-N 0.000 claims description 3
- RURHILYUWQEGOS-VOTSOKGWSA-N 4-Methylcinnamic acid Chemical compound CC1=CC=C(\C=C\C(O)=O)C=C1 RURHILYUWQEGOS-VOTSOKGWSA-N 0.000 claims description 3
- GXLIFJYFGMHYDY-ZZXKWVIFSA-N 4-chlorocinnamic acid Chemical compound OC(=O)\C=C\C1=CC=C(Cl)C=C1 GXLIFJYFGMHYDY-ZZXKWVIFSA-N 0.000 claims description 3
- BBYDXOIZLAWGSL-UHFFFAOYSA-N 4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1 BBYDXOIZLAWGSL-UHFFFAOYSA-N 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 3
- UODHHVJEXWSPFU-UHFFFAOYSA-N 5-(4-methoxyphenyl)penta-2,4-dienoic acid Chemical compound COC1=CC=C(C=CC=CC(O)=O)C=C1 UODHHVJEXWSPFU-UHFFFAOYSA-N 0.000 claims description 3
- 239000005711 Benzoic acid Substances 0.000 claims description 3
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 3
- TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Natural products CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 claims description 3
- ILUJQPXNXACGAN-UHFFFAOYSA-N O-methylsalicylic acid Chemical compound COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 claims description 3
- 235000021314 Palmitic acid Nutrition 0.000 claims description 3
- 235000021355 Stearic acid Nutrition 0.000 claims description 3
- 235000010233 benzoic acid Nutrition 0.000 claims description 3
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 claims description 3
- FEIQOMCWGDNMHM-UHFFFAOYSA-N cinnamylideneacetic acid Natural products OC(=O)C=CC=CC1=CC=CC=C1 FEIQOMCWGDNMHM-UHFFFAOYSA-N 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- YAQXGBBDJYBXKL-UHFFFAOYSA-N iron(2+);1,10-phenanthroline;dicyanide Chemical compound [Fe+2].N#[C-].N#[C-].C1=CN=C2C3=NC=CC=C3C=CC2=C1.C1=CN=C2C3=NC=CC=C3C=CC2=C1 YAQXGBBDJYBXKL-UHFFFAOYSA-N 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 claims description 3
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- AFDXODALSZRGIH-UHFFFAOYSA-N p-coumaric acid methyl ether Natural products COC1=CC=C(C=CC(O)=O)C=C1 AFDXODALSZRGIH-UHFFFAOYSA-N 0.000 claims description 3
- 235000019260 propionic acid Nutrition 0.000 claims description 3
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 3
- 239000000575 pesticide Substances 0.000 claims description 2
- 239000002994 raw material Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 claims 1
- 241001124076 Aphididae Species 0.000 abstract description 6
- 239000005664 Spirodiclofen Substances 0.000 abstract description 4
- 230000000749 insecticidal effect Effects 0.000 abstract description 4
- 231100000053 low toxicity Toxicity 0.000 abstract description 4
- 239000013641 positive control Substances 0.000 abstract description 4
- DTDSAWVUFPGDMX-UHFFFAOYSA-N spirodiclofen Chemical compound CCC(C)(C)C(=O)OC1=C(C=2C(=CC(Cl)=CC=2)Cl)C(=O)OC11CCCCC1 DTDSAWVUFPGDMX-UHFFFAOYSA-N 0.000 abstract description 4
- 230000002147 killing effect Effects 0.000 abstract description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 86
- 238000005160 1H NMR spectroscopy Methods 0.000 description 43
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
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- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 2
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Classifications
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- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
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- A—HUMAN NECESSITIES
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- 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
- A01N43/24—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 two or more hetero atoms
- A01N43/26—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 two or more hetero atoms five-membered rings
- A01N43/28—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 two or more hetero atoms five-membered rings with two hetero atoms in positions 1,3
- A01N43/30—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 two or more hetero atoms five-membered rings with two hetero atoms in positions 1,3 with two oxygen atoms in positions 1,3, condensed with a carbocyclic ring
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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
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Abstract
本发明公开了一种胡椒碱肟酯类衍生物，该化合物的通式如下式所示：
其中：R1选自氢，且R2选自氯；或R1选自氢，且R2选自甲氧基；或R1R2选自二氧亚甲基；或R1R2选自二氧亚乙基；R3选自烷基、取代或非取代苯基、取代或非取代肉桂基、5‑(取代或非取代苯基)‑2,4‑戊二烯基的一种；本发明制备的的胡椒碱肟酯类衍生物中部分化合物具有与阳性对照螺螨酯相当的杀螨活性；部分化合物具有较好的杀蚜虫活性，与母体胡椒碱相比其杀虫活性显著提高，可于制备高效、环保、低毒的植物源杀虫/螨剂。
Description
技术领域
本发明属于有机合成技术领域，具体涉及一种胡椒碱肟酯类衍生物、制备及应用。
背景技术
胡椒碱(Piperine，)是一种从胡椒科植物中提取的一种桂皮酰胺类生物碱。其结构包含二氧亚甲基芳杂环(A)，脂肪烯烃链(B)和酰胺片段(C)。由于烯烃链的存在，胡椒碱有多种同分异构体如：异胡椒碱、胡椒脂碱、异胡椒脂碱。此外，研究表明胡椒属植物中还有多种胡椒碱类似物如：胡椒林碱、胡椒新碱、胡椒亭碱、胡椒油碱A和胡椒油碱B等，而胡椒碱在胡椒所有的生物碱中含量最大，活性也最高，因此备受关注。
胡椒碱具有广泛的生物活性。在医药领域的活性研究发现，胡椒碱具有抗肿瘤【Cancer Letters,357(1):129-140】、消炎【International Immunopharmacology,65:448-457】、提高药物生物利用度【Phytomedicine,54:98-108】和改善阿尔兹海默症【Journal ofNutritional Biochemistry,70:147-155】等生物活性；在农用领域的研究发现，胡椒碱具有抑菌【Drug Development and Industrial Pharmacy,41(6):989-994】，杀虫【Bioorganic Chemistry,94:103464】等农用活性。
胡椒碱在结构优化方面也有很多报道。例如，2015年，Qu等在胡椒碱酰胺部分引入磺酰腙片段，发现其衍生物对东方粘虫有麻醉作用【Scientific Reports,5,13077】；2018年，Yang等在胡椒碱酰胺片段引入异恶唑啉/吡唑啉片段，并评价其对常见农业害虫东方粘虫和朱砂叶螨的杀虫/螨活性【Journal of Agricultural and Food Chemistry.2018,66,11254-11264】；但用三氯氧磷在胡椒碱C-2位置引入醛基还未见报道。
发明内容
针对上述现有技术不足与缺陷，本发明的目的在于，提供一种胡椒碱肟酯类衍生物、制备及应用，解决现有技术中缺少一种可以杀虫/螨的胡椒碱肟酯类衍生物的技术问题。
为了达到上述目的，本申请采用如下技术方案予以实现：一种胡椒碱肟酯类衍生物，该化合物的通式如下式所示：
其中：R1选自氢，且R2选自氯；或R1选自氢，且R2选自甲氧基；或R1R2选自二氧亚甲基；或R1R2选自二氧亚乙基；R3选自烷基、取代或非取代苯基、取代或非取代肉桂基、5-(取代或非取代苯基)-2,4-戊二烯基的一种；
所述的胡椒碱肟酯类衍生物具有以下结构之一：
(1):R1R2＝二氧亚甲基；R3＝CH3；
(2):R1R2＝二氧亚甲基；R3＝CH2CH3；
(3):R1R2＝二氧亚甲基；R3＝(CH2)4CH3；
(4):R1R2＝二氧亚甲基；R3＝(CH2)10CH3；
(5):R1R2＝二氧亚甲基；R3＝(CH2)11CH3；
(6):R1R2＝二氧亚甲基；R3＝(CH2)12CH3；
(7):R1R2＝二氧亚甲基；R3＝(CH2)13CH3；
(8):R1R2＝二氧亚甲基；R3＝(CH2)14CH3；
(9):R1R2＝二氧亚甲基；R3＝(CH2)16CH3；
(10):R1R2＝二氧亚甲基；R3＝苯基；
(11):R1R2＝二氧亚甲基；R3＝肉桂基；
(12):R1 R2＝二氧亚甲基；R3＝5-苯基-2,4-戊二烯基；
(13):R1R2＝二氧亚甲基；R3＝对氟苯基；
(14):R1R2＝二氧亚甲基；R3＝对氟肉桂基；
(15):R1R2＝二氧亚甲基；R3＝5-(对氟苯基)-2,4-戊二烯基；
(16):R1R2＝二氧亚甲基；R3＝对氯苯基；
(17):R1R2＝二氧亚甲基；R3＝对氯肉桂基；
(18):R1R2＝二氧亚甲基；R3＝5-(对氯苯基)-2,4-戊二烯基；
(19):R1R2＝二氧亚甲基；R3＝对甲基苯基；
(20):R1R2＝二氧亚甲基；R3＝对甲基肉桂基；
(21):R1R2＝二氧亚甲基；R3＝5-(对甲基苯基)-2,4-戊二烯基；
(22):R1R2＝二氧亚甲基；R3＝对甲氧基苯基；
(23):R1R2＝二氧亚甲基；R3＝对甲氧基肉桂基；
(24):R1R2＝二氧亚甲基；R3＝5-(对甲氧基苯基)-2,4-戊二烯基；
(25):R1R2＝二氧亚甲基；R3＝3,4-(二氧亚甲基)苯基；
(26):R1R2＝二氧亚甲基；R3＝3,4-(二氧亚甲基)肉桂基；
(27):R1R2＝二氧亚甲基；R3＝5-(3,4-(二氧亚甲基)苯基)-2,4-戊二烯基；
(28):R1R2＝二氧亚甲基；R3＝3,4-(二氧亚乙基)苯基；
(29):R1R2＝二氧亚甲基；R3＝3,4-(二氧亚乙基)肉桂基；
(30):R1R2＝二氧亚甲基；R3＝5-(3,4-(二氧亚乙基)苯基)-2,4-戊二烯基；
(31):R1R2＝二氧亚甲基；R3＝邻氯苯基；
(32):R1R2＝二氧亚甲基；R3＝间氯苯基；
(33):R1R2＝二氧亚甲基；R3＝邻甲氧基苯基；
(34):R1R2＝二氧亚甲基；R3＝间甲氧基苯基；
(35):R1＝H；R2＝氯；R3＝对氯苯基；
(36):R1＝H；R2＝氯；R3＝3,4-(二氧亚甲基)肉桂基；
(37):R1＝H；R2＝氯；R3＝(CH2)12CH3；
(38):R1＝H；R2＝甲氧基；R3＝对氯苯基；
(39):R1＝H；R2＝甲氧基；R3＝3,4-(二氧亚甲基)肉桂基；
(40):R1＝H；R2＝甲氧基；R3＝(CH2)12CH3；
(41):R1R2＝二氧亚乙基；R3＝对氯苯基；
(42):R1R2＝二氧亚乙基；R3＝3,4-(二氧亚甲基)肉桂基；
(43):R1R2＝二氧亚乙基；R3＝(CH2)12CH3。
一种胡椒碱肟酯类衍生物的制备方法，包括如下步骤：
步骤一：以下式所示胡椒碱类化合物为原料，
与三氯氧磷反应制得中间体，所述中间体结构式如下式所示：
其中，R1选自氢，且R2选自氯；或R1选自氢，且R2选自甲氧基；或R1R2选自二氧亚甲基；或R1R2选自二氧亚乙基；
步骤二：中间体与盐酸羟胺反应，得到肟类中间体，所述肟类中间体结构式如下式所示：
步骤三：肟类中间体与R3COOH反应，得到胡椒碱肟酯类衍生物，R3选自烷基、取代或非取代苯基、取代或非取代肉桂基、5-(取代或非取代苯基)-2,4-戊二烯基。
步骤一中的反应在N,N-二甲基甲酰胺(DMF)溶液中进行，反应温度为0-90℃。步骤二中的反应在乙醇溶液中进行，同时加入盐酸羟胺和氢氧化钠，反应温度20-30℃。
步骤三中的R3COOH选自乙酸、丙酸、己酸、十二酸、十三酸、十四酸、十五酸、十六酸、十八酸、苯甲酸、肉桂酸、5-苯基-2,4-戊二烯基酸、对氟苯甲酸、对氟肉桂酸、5-(4-氟苯基)-2,4-戊二烯基酸、邻氯苯甲酸、间氯苯甲酸、对氯苯甲酸、对氯肉桂酸、5-(4-氯苯基)-2,4-戊二烯基酸、对甲基苯甲酸、对甲基肉桂酸、5-(4-甲基苯基)-2,4-戊二烯基酸、邻甲氧基苯甲酸、间甲氧基苯甲酸、对甲氧基苯甲酸、对甲氧基肉桂酸、5-(4-甲氧基苯基)-2,4-戊二烯基酸、胡椒酸、3,4-(二氧亚甲基)肉桂基酸、5-(3,4-(二氧亚甲基)苯基)-2,4-戊二烯基酸、3,4-二氧亚乙基苯甲酸、3,4-(二氧亚乙基)肉桂基酸、5-(3,4-(二氧亚乙基)苯基)-2,4-戊二烯基酸的一种；
步骤三的反应在无水二氯甲烷中进行，同时加入EDCI和DMAP，反应温度为20-30℃。
上述的胡椒碱肟酯类衍生物作为杀虫剂的应用。
上述的胡椒碱肟酯类衍生物作为杀螨剂的应用。
上述的胡椒碱肟酯类衍生物的制备方法制备的胡椒碱肟酯类衍生物作为杀虫剂的应用。
上述的胡椒碱肟酯类衍生物的制备方法制备的胡椒碱肟酯类衍生物作为杀螨剂的应用。
本发明与现有技术相比，有益的技术效果是：
(Ⅰ)本发明制备的胡椒碱肟酯类衍生物中部分化合物具有与阳性对照螺螨酯相当的杀螨活性；部分化合物具有较好的杀蚜虫活性，与母体胡椒碱相比其杀虫活性显著提高，可于制备高效、环保、低毒的植物源杀虫/螨剂。
(Ⅱ)本发明的制备方法工艺简单、成本低。
附图说明
图1为化合物6的核磁共振氢谱谱图；
图2为化合物16的核磁共振氢谱谱图；
图3为化合物36的核磁共振氢谱谱图；
图4为化合物43的核磁共振氢谱谱图；
图5为合成路线图。
以下结合附图和实施例对本发明的具体内容作进一步详细解释说明。
具体实施方式
以下给出本发明的具体实施例，需要说明的是本发明并不局限于以下具体实施例，凡在本申请技术方案基础上做的等同变换均落入本发明的保护范围。
胡椒碱肟酯类衍生物的制备：本发明所述胡椒碱肟酯类衍生物的合成路线如图5所示：依据上述合成路线：
首先将等当量三氯氧磷与DMF在冰浴中搅拌，再将适量胡椒碱类化合物(a-d)溶于合适溶剂(如DMF)中，然后加入三氯氧磷与DMF混合溶液中，合适条件(如90℃油浴)下，制得中间体(e-h)；
其次中间体(e-h)与适量盐酸羟胺和氢氧化钠在合适条件(如反应温度为20-30℃)下反应，得到中间体(i-l)；适量中间体(i-l)与有机酸R3COOH在合适反应体系(如存在1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDCI)、4-二甲氨基吡啶(DMAP)和无水二氯甲烷的反应体系)和反应条件(如反应温度为20-30℃)下反应制得本发明的化合物。
所述R3COOH选自乙酸、丙酸、己酸、十二酸、十三酸、十四酸、十五酸、十六酸、十八酸、苯甲酸、肉桂酸、5-苯基-2,4-戊二烯基酸、对氟苯甲酸、对氟肉桂酸、5-(4-氟苯基)-2,4-戊二烯基酸、邻氯苯甲酸、间氯苯甲酸、对氯苯甲酸、对氯肉桂酸、5-(4-氯苯基)-2,4-戊二烯基酸、对甲基苯甲酸、对甲基肉桂酸、5-(4-甲基苯基)-2,4-戊二烯基酸、邻甲氧基苯甲酸、间甲氧基苯甲酸、对甲氧基苯甲酸、对甲氧基肉桂酸、5-(4-甲氧基苯基)-2,4-戊二烯基酸、胡椒酸、3,4-(二氧亚甲基)肉桂基酸、5-(3,4-(二氧亚甲基)苯基)-2,4-戊二烯基酸、3,4-二氧亚乙基苯甲酸、3,4-(二氧亚乙基)肉桂基酸、5-(3,4-(二氧亚乙基)苯基)-2,4-戊二烯基酸的一种；
实施例1：制备胡椒碱肟酯类衍生物1-43化合物
中间体(e-h)的制备方法：在冰浴条件下加入DMF(10mmol)和三氯氧磷(10mmol)于100mL圆底烧瓶中，搅拌0.5小时，再称取胡椒碱类化合物(a-d，2mmol)溶于DMF(5mL)中，逐滴加入反应液中，再置于90℃油浴搅拌3-12小时。反应完全后，在冰浴条件下用20％氢氧化钠水溶液调Ph至9-10，过滤，滤饼烘干，柱层析分离的中间体(e-h)，产率55-90％。
中间体(i-l)的制备方法：称取盐酸羟胺(3mmol)和氢氧化钠(3mmol)溶于10mL乙醇中，在室温条件下搅拌15分钟，在称取中间体(e-h，1mmol)加入上述反应液中，继续搅拌5-18小时，反应完全后加入20mL水，再用乙酸乙酯(40mL×3)萃取，合并有机相，干燥，浓缩，柱层析分离得到中间体(i-l)，产率47-66％。
目标化合物1-43的制备方法：中间体(i-l，0.2mmol)，R3COOH(0.3mmol)，EDCI(0.3mmol)和DMAP(0.04mmol)溶于无水二氯甲烷(5mL)中，室温搅拌4-12h；反应完全后加入乙酸乙酯(30mL)稀释，再依次加入0.1M盐酸水溶液(15mL)，5％碳酸氢钠水溶液(15mL)和饱和食盐水洗涤(15mL)，有机相干燥浓缩，薄层层析分离得目标化合物1-43(产率28-83％)。
上述制备方法制备得到的化合物1-43具有以下通式，且分别对应具有(1)～(43)结构的化合物。
(1):R1R2＝二氧亚甲基；R3＝CH3；(2):R1R2＝二氧亚甲基；R3＝CH2CH3；(3):R1R2＝二氧亚甲基；R3＝(CH2)4CH3；(4):R1R2＝二氧亚甲基；R3＝(CH2)10CH3；(5):R1R2＝二氧亚甲基；R3＝(CH2)11CH3；(6):R1R2＝二氧亚甲基；R3＝(CH2)12CH3；(7):R1R2＝二氧亚甲基；R3＝(CH2)13CH3；(8):R1R2＝二氧亚甲基；R3＝(CH2)14CH3；(9):R1R2＝二氧亚甲基；R3＝(CH2)16CH3；(10):R1R2＝二氧亚甲基；R3＝苯基；(11):R1R2＝二氧亚甲基；R3＝肉桂基；(12):R1 R2＝二氧亚甲基；R3＝5-苯基-2,4-戊二烯基；(13):R1R2＝二氧亚甲基；R3＝对氟苯基；(14):R1R2＝二氧亚甲基；R3＝对氟肉桂基；(15):R1R2＝二氧亚甲基；R3＝5-(对氟苯基)-2,4-戊二烯基；(16):R1R2＝二氧亚甲基；R3＝对氯苯基；(17):R1R2＝二氧亚甲基；R3＝对氯肉桂基；(18):R1R2＝二氧亚甲基；R3＝5-(对氯苯基)-2,4-戊二烯基；(19):R1R2＝二氧亚甲基；R3＝对甲基苯基；(20):R1R2＝二氧亚甲基；R3＝对甲基肉桂基；(21):R1R2＝二氧亚甲基；R3＝5-(对甲基苯基)-2,4-戊二烯基；(22):R1R2＝二氧亚甲基；R3＝对甲氧基苯基；(23):R1R2＝二氧亚甲基；R3＝对甲氧基肉桂基；(24):R1R2＝二氧亚甲基；R3＝5-(对甲氧基苯基)-2,4-戊二烯基；(25):R1R2＝二氧亚甲基；R3＝3,4-(二氧亚甲基)苯基；(26):R1R2＝二氧亚甲基；R3＝3,4-(二氧亚甲基)肉桂基；(27):R1R2＝二氧亚甲基；R3＝5-(3,4-(二氧亚甲基)苯基)-2,4-戊二烯基；(28):R1R2＝二氧亚甲基；R3＝3,4-(二氧亚乙基)苯基；(29):R1R2＝二氧亚甲基；R3＝3,4-(二氧亚乙基)肉桂基；(30):R1R2＝二氧亚甲基；R3＝5-(3,4-(二氧亚乙基)苯基)-2,4-戊二烯基；(31):R1R2＝二氧亚甲基；R3＝邻氯苯基；(32):R1R2＝二氧亚甲基；R3＝间氯苯基；(33):R1R2＝二氧亚甲基；R3＝邻甲氧基苯基；(34):R1R2＝二氧亚甲基；R3＝间甲氧基苯基；(35):R1＝H；R2＝氯；R3＝对氯苯基；(36):R1＝H；R2＝氯；R3＝3,4-(二氧亚甲基)肉桂基；(37):R1＝H；R2＝氯；R3＝(CH2)12CH3；(38):R1＝H；R2＝甲氧基；R3＝对氯苯基；(39):R1＝H；R2＝甲氧基；R3＝3,4-(二氧亚甲基)肉桂基；(40):R1＝H；R2＝甲氧基；R3＝(CH2)12CH3；(41):R1R2＝二氧亚乙基；R3＝对氯苯基；(42):R1R2＝二氧亚乙基；R3＝3,4-(二氧亚甲基)肉桂基；(43):R1R2＝二氧亚乙基；R3＝(CH2)12CH3。
化合物1的理化性质如下：
1)黄色固体，熔点160-162℃；收率51％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):3410,2934,2860,1749,1619,1442,1255,1212,809；1HNMR(500MHz,CDCl3)δ:7.97(s,1H),6.97(d,J＝1.5Hz,1H),6.89(dd,J＝1.5,8.0Hz,1H),6.67-6.80(m,4H),5.97-6.00(m,2H),3.73-3.76(m,2H),3.33(t,J＝5.0Hz,2H),2.19(s,3H),1.56-1.69(m,6H)；HRMS[ESI]:calcd for C20H22N2NaO5([M+Na]+),393.1426；found,393.1415.
化合物2的理化性质如下：
1)黄色固体，熔点164-166℃；收率71％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2935,2860,1770,1623,1255,1198,809,722；1H NMR(500MHz,CDCl3)δ:7.97(s,1H),6.97(s,1H),6.89(d,J＝8.0Hz,1H),6.66-6.79(m,4H),5.99(s,2H),3.73-3.76(m,2H),3.32-3.35(m,2H),2.45-2.49(m,2H),1.58-1.69(m,6H),1.18(t,J＝7.0Hz,3H)；HRMS[ESI]:calcd for C21H24N2NaO5([M+Na]+),407.1583；found,407.1564.
化合物3的理化性质如下：
1)黄色固体，熔点149-151℃；收率52％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):3063,2935,2863,1771,1613,1256,1212,1041,810,720；1HNMR(500MHz,CDCl3)δ:7.96(s,1H),6.97(s,1H),6.89(d,J＝8.0Hz,1H),6.66-6.79(m,4H),5.99(s,2H),3.73-3.77(m,2H),3.33-3.35(m,2H),2.41-2.44(m,2H),1.58-1.69(m,8H),1.32-1.35(m,4H),0.89-0.91(m,3H)；HRMS[ESI]:calcd for C24H30N2NaO5([M+Na]+),449.2052；found,449.2030.
化合物4的理化性质如下：
1)黄色固体，熔点151-153℃；收率54％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):3062,2921,2855,1771,1613,1444,1255,1106,810,717；1HNMR(500MHz,CDCl3)δ:7.96(s,1H),6.97(s,1H),6.89(d,J＝8.0Hz,1H,Ar-H),6.66-6.79(m,4H),5.97-6.00(m,2H),3.73-3.76(m,2H),3.33-3.35(m,2H),2.41(t,J＝7.5Hz,2H),1.59-1.70(m,8H),1.26-1.34(m,16H),0.86(t,J＝7.0Hz,3H)；HRMS[ESI]:calcd forC30H42N2NaO5([M+Na]+),533.2991；found,533.2972.
化合物5的理化性质如下：
1)黄色固体，熔点151-153℃；收率64％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2920,2854,1772,1613,1446,1257,1134,811,718；1H NMR(500MHz,CDCl3)δ:7.96(s,1H),6.97(s,1H),6.89(d,8.0Hz,1H),6.66-6.79(m,4H),5.98-6.00(m,2H),3.73-3.77(m,2H),3.33-3.36(m,2H),2.41(t,J＝7.5Hz,2H),1.57-1.69(m,8H),1.25-1.34(m,18H),0.86(t,J＝7.0Hz,3H)；HRMS[ESI]:calcd for C31H44N2NaO5([M+Na]+),547.3148；found,547.3123.
化合物6的理化性质如下：
1)黄色固体，熔点145-147℃；收率49％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):3061,2919,2853,1773,1613,1445,1256,1194,1111,811,718；1HNMR(500MHz,CDCl3)δ:7.96(s,1H),6.96(s,1H),6.89(dd,J＝1.5,8.0Hz,1H,Ar-H),6.66-6.79(m,4H),5.97-6.00(m,2H),3.74-3.76(m,2H),3.33-3.35(m,2H),2.41(t,J＝8.0Hz,2H),1.59-1.67(m,8H),1.25-1.34(m,20H),0.86(t,J＝7.0Hz,3H)；HRMS[ESI]:calcd forC32H46N2NaO5([M+Na]+),561.3304；found,561.3272.
化合物7的理化性质如下：
1)黄色固体，熔点141-143℃；收率64％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2920,2853,1772,1617,1446,1257,1196,1100,810,717；1HNMR(500MHz,CDCl3)δ:7.96(s,1H),6.97(s,1H),6.89(d,J＝8.0Hz,1H),6.66-6.81(m,4H),5.98-6.00(m,2H),3.73-3.77(m,2H),3.33-3.35(m,2H),2.41(t,J＝7.5Hz,2H),1.59-1.67(m,8H),1.25-1.34(m,22H),0.86(t,J＝7.0Hz,3H)；HRMS[ESI]:calcd for C33H48N2NaO5([M+Na]+),575.3461；found,575.3420.
化合物8的理化性质如下：
1)黄色固体，熔点118-120℃；收率45％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2918,2851,1771,1613,1444,1256,1129,812,719；1H NMR(500MHz,CDCl3)δ:7.97(s,1H),6.97(s,1H),6.89(d,J＝8.0Hz,1H),6.66-6.79(m,4H),5.98-6.00(m,2H),3.73-3.77(m,2H),3.33-3.35(m,2H),2.41(t,J＝7.5Hz,2H),1.58-1.69(m,8H),1.25-1.34(m,24H),0.86(t,J＝7.0Hz,3H)；HRMS[ESI]:calcd for C34H50N2NaO5([M+Na]+),589.3617；found,589.3589.
化合物9的理化性质如下：
1)黄色固体，熔点126-128℃；收率48％；
2)该化合物的红外光谱图、核磁共振谱图特征
IR cm-1(KBr):2918,2850,1772,1614,1445,1256,1099,811,718；1H NMR(500MHz,CDCl3)δ:7.96(s,1H),6.97(d,J＝1.5Hz,1H),6.89(dd,J＝1.5,8.0Hz,1H),6.66-6.80(m,4H),5.98-6.00(m,2H),3.73-3.77(m,2H),3.33-3.35(m,2H),2.41(t,J＝7.5Hz,2H),1.58-1.70(m,8H),1.25-1.34(m,28H),0.86(t,J＝7.0Hz,3H)；HRMS[ESI]:calcd forC36H54N2NaO5([M+Na]+),617.3930；found,617.3900.
化合物10的理化性质如下：
1)黄色固体，熔点159-161℃；收率57％；
2)该化合物的红外光谱图、核磁共振谱图特征
IR cm-1(KBr):3068,2927,2856,1744,1626,1443,1248,1187,809,705；1HNMR(500MHz,CDCl3)δ:8.16(s,1H),8.06(d,J＝7.5Hz,2H),7.58-7.61(m,1H),7.45(t,J＝7.5Hz,2H),6.98(s,1H),6.91(d,J＝8.0Hz,1H),6.73-6.83(m,4H),5.99(s,2H),3.77-3.80(m,2H),3.39-3.42(m,2H),1.60-1.73(m,6H)；HRMS[ESI]:calcd for C25H24N2NaO5([M+Na]+),455.1583；found,455.1565.
化合物11的理化性质如下：
1)黄色固体，熔点184-186℃；收率58％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):3033,2931,2859,1742,1622,1441,1254,1192,1040,811,709；1HNMR(500MHz,CDCl3)δ:8.07(s,1H),7.79(d,J＝16.0Hz,1H),7.54-7.55(m,2H),7.39-7.41(m,3H),6.98(s,1H),6.90(J＝8.0Hz,1H),6.73-6.83(m,4H),6.54(J＝16.0Hz,1H),5.97-6.00(m,2H),3.76-3.80(m,2H),3.36-3.38(m,2H),1.58-1.68(m,6H)；HRMS[ESI]:calcdfor C27H26N2NaO5([M+Na]+),481.1739；found,481.1725.
化合物12的理化性质如下：
1)黄色固体，熔点158-160℃；收率43％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2929,2855,1736,1626,1221,1096,809,691；1H NMR(500MHz,CDCl3)δ:8.04(s,1H),7.54-7.59(m,1H),7.47(d,J＝7.0Hz,2H),7.32-7.38(m,3H),6.90-6.98(m,4H),6.71-6.82(m,4H),6.10(d,J＝15.5Hz,1H),5.97-6.00(m,2H),3.76-3.79(m,2H),3.35-3.38(m,2H),1.61-1.71(m,6H)；HRMS[ESI]:calcd for C29H28N2NaO5([M+Na]+),507.1896；found,507.1871.
化合物13的理化性质如下：
1)黄色固体，熔点170-172℃；收率35％；
2)该化合物的红外光谱图、核磁共振谱图特征
IR cm-1(KBr):3072,2932,2859,1745,1602,1444,1251,1120,811,726；1HNMR(500MHz,CDCl3)δ:8.15(s,1H),8.07-8.10(m,2H),7.12(t,J＝8.5Hz,2H),6.98(s,1H),6.91(d,J＝8.0Hz,1H),6.73-6.83(m,4H),5.99-6.00(m,2H),3.77-3.80(m,2H),3.38-3.41(m,2H),1.66-1.72(m,6H)；HRMS[ESI]:calcd for C25H23FN2NaO5([M+Na]+),473.1489；found,473.1466.
化合物14的理化性质如下：
1)黄色固体，熔点199-201℃；收率48％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2930,2859,1743,1624,1442,1254,1124,821,727；1H NMR(500MHz,CDCl3)δ:8.06(s,1H),7.75(d,J＝16.0Hz,1H),7.52-7.55(m,2H),7.07(t,J＝8.5Hz,2H),6.98(s,1H),6.90-6.92(m,1H),6.71-6.83(m,4H),6.44-6.50(s,1H),5.97-6.00(m,2H),3.74-3.81(m,2H),3.33.3.40(m,2H),1.60-1.71(m,6H)；HRMS[ESI]:calcd forC27H25FN2NaO5([M+Na]+),499.1645；found,499.1620.
化合物15的理化性质如下：
1)黄色固体，熔点161-163℃；收率83％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):3063,2935,2859,1734,1624,1441,1231,1100,808,726；1HNMR(500MHz,CDCl3)δ:8.04(s,1H),7.52(dd,J＝11.0,15.5Hz,1H),7.44-7.47(m,2H),7.04(t,J＝8.5Hz,2H),6.98(s,1H),6.89-6.92(m,2H),6.69-6.84(m,5H),6.10(d,J＝15.0Hz,1H),5.97-6.00(m,2H),3.75-3.80(m,2H),3.34-3.39(m,2H),1.62-1.72(m,6H)；HRMS[ESI]:calcd for C29H27FN2NaO5([M+Na]+),525.1802；found,525.1777.
化合物16的理化性质如下：
1)黄色固体，熔点190-192℃；收率41％；
2)该化合物的红外光谱图、核磁共振谱图特征
IR cm-1(KBr):2938,2860,1744,1623,1443,1251,1054,809,746；1H NMR(500MHz,CDCl3)δ:8.15(s,1H),7.99(d,J＝8.5Hz,2H),7.43(d,J＝8.5Hz,2H),6.98(s,1H),6.91(d,J＝8.0Hz,1H),6.73-6.83(m,4H),5.98-6.00(m,2H),3.76-3.81(m,2H),3.37-3.41(m,2H),1.62-1.73(m,6H)；HRMS[ESI]:calcd for C25H23ClN2NaO5([M+Na]+),489.1193；found,489.1167.
化合物17的理化性质如下：
1)黄色固体，熔点211-213℃；收率44％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):3064,2932,2858,1738,1620,1440,1252,1120,813,726；1HNMR(500MHz,CDCl3)δ:8.06(s,1H),7.73(d,J＝16.0Hz,1H),7.47(d,J＝8.0Hz,2H),7.36(d,J＝8.0Hz,2H),6.98(s,1H),6.90(d,J＝8.0Hz,1H),6.71-6.81(m,4H),6.51(d,J＝16.0Hz,1H),5.96-6.00(m,2H),3.74-3.81(m,2H),3.35-3.39(m,2H),1.59-1.71(m,6H)；HRMS[ESI]:calcd for C27H25ClN2NaO5([M+Na]+),515.1350；found,515.1316.
化合物18的理化性质如下：
1)黄色固体，熔点167-169℃；收率62％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2932,2858,1738,1619,1441,1254,1095,808,705；1H NMR(500MHz,CDCl3)δ:8.04(s,1H),7.51-7.56(m,1H),7.39(d,J＝8.5Hz,2H),7.32(d,J＝8.5Hz,2H),6.86-6.99(m,4H),6.76-6.81(m,3H),6.69-6.74(m,1H),6.11(d,J＝15.5Hz,1H),5.99(s,2H),3.75-3.80(m,2H),3.35-3.38(m,2H),1.61-1.71(m,6H)；HRMS[ESI]:calcd forC29H27ClN2NaO5([M+Na]+),541.1506；found,541.1476.
化合物19的理化性质如下：
1)黄色固体，熔点195-197℃；收率33％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):3068,2925,2857,1735,1623,1442,1249,1112,1030,802,728；1HNMR(500MHz,CDCl3)δ:8.15(s,1H),7.94-7.96(m,2H),7.25-7.27(m,2H),6.98(s,1H),6.90(d,J＝8.0Hz,1H),6.73-6.83(m,4H),5.99(s,2H),3.76-3.80(m,2H),3.38-3.42(m,2H),2.42(s,3H),1.63-1.72(m,6H)；HRMS[ESI]:calcd for C26H26N2NaO5([M+Na]+),469.1739；found,469.1713.
化合物20的理化性质如下：
1)黄色固体，熔点194-196℃；收率39％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2929,2857,1734,1619,1440,1252,1108,807,720；1H NMR(500MHz,CDCl3)δ:8.06(s,1H),7.77(d,J＝16.0Hz,1H),7.43(d,J＝8.0Hz,2H),7.19(t,J＝7.5Hz,2H),6.98(d,J＝1.5Hz,1H),6.90(dd,J＝1.5,8.0Hz,1H),6.70-6.83(m,4H),6.50(d,J＝16.0Hz,1H),5.99(s,2H),3.74-3.82(m,2H),3.36-3.39(m,2H),2.38(s,3H),1.60-1.72(m,6H)；HRMS[ESI]:calcd for C28H28N2NaO5([M+Na]+),495.1896；found,495.1863.
化合物21的理化性质如下：
1)黄色固体，熔点155-157℃；收率54％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):3018,2924,2857,1737,1618,1442,1246,1195,1102,806,721；1HNMR(500MHz,CDCl3)δ:8.04(s,1H),7.53(dd,J＝10.5,15.5Hz,1H),7.36(d,J＝8.0Hz,2H),7.16(d,J＝8.0Hz,2H),6.97(s,1H),6.85-6.93(m,3H),6.69-6.83(m,4H),6.07(d,J＝15.0Hz,1H),5.99(s,2H),3.75-3.79(m,2H),3.35-3.38(m,2H),2.36(s,3H),1.61-1.70(m,6H)；HRMS[ESI]:calcd for C30H30N2NaO5([M+Na]+),521.2052；found,521.2028.
化合物22的理化性质如下：
1)黄色固体，熔点161-163℃；收率48％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):3005,2934,2857,1740,1618,1442,1249,1042,808,726；1HNMR(500MHz,CDCl3)δ:8.14(s,1H),8.10(d,J＝8.0Hz,2H),6.90-6.98(m,4H),6.73-6.83(m,4H),5.99(s,2H),3.73-3.87(m,5H),3.33-3.44(m,2H),1.60-1.74(m,6H)；HRMS[ESI]:calcd for C26H26N2NaO6([M+Na]+),485.1689；found,485.1666.
化合物23的理化性质如下：
1)黄色固体，熔点174-176℃；收率54％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2929,2855,1734,1615,1438,1253,1177,817,727；1H NMR(500MHz,CDCl3)δ:8.05(s,1H),7.75(d,J＝16.0Hz,1H),7.49(d,J＝8.0Hz,2H),6.90-6.98(m,4H),6.72-6.83(m,4H),6.41(d,J＝16.0Hz,1H),5.98-6.00(m,2H),3.74-3.84(m,5H),3.36-3.38(m,2H),1.59-1.72(m,6H)；HRMS[ESI]:calcd for C28H28N2NaO6([M+Na]+),511.1845；found,511.1823.
化合物24的理化性质如下：
1)黄色固体，熔点168-170℃；收率53％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):3022,2935,2856,1735,1614,1442,1254,1176,1036,810,707；1HNMR(500MHz,CDCl3)δ:8.03(s,1H),7.53(dd,J＝11.0,15.0Hz,1H),7.41(d,J＝8.5Hz,2H),6.97(s,1H),6.88-6.91(m,4H),6.68-6.80(m,5H),6.04(d,J＝15.0Hz,1H),5.98(s,2H),3.75-3.83(m,5H),3.35-3.38(m,2H),1.60-1.72(m,6H)；HRMS[ESI]:calcd forC30H30N2NaO6([M+Na]+),537.2002；found,537.1977.
化合物25的理化性质如下：
1)黄色固体，熔点88-90℃；收率48％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):3069,2930,2859,1738,1622,1256,1104,813,720；1H NMR(500MHz,CDCl3)δ:8.13(s,1H),7.66(d,J＝8.0Hz,1H),7.47(s,1H),6.98(s,1H),6.90(d,J＝8.0Hz,1H),6.85-6.86(m,1H),6.72-6.79(m,4H),6.04-6.05(m,2H),5.98-5.99(m,2H),3.76-3.80(m,2H),3.37-3.41(m,2H),159-1.73(m,6H)；HRMS[ESI]:calcd for C26H24N2NaO7([M+Na]+),499.1481；found,499.1451.
化合物26的理化性质如下：
1)黄色固体，熔点200-202℃；收率28％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2923,2856,1735,1623,1250,1113,801,730；1H NMR(500MHz,CDCl3)δ:8.05(s,1H),7.69(d,J＝16.0Hz,1H),6.98-7.05(m,3H),6.90(d,J＝8.0Hz,1H),6.72-6.83(m,5H),6.36(d,J＝15.5Hz,1H),5.99-6.03(m,4H),3.75-3.80(m,2H),3.35-3.90(m,2H),1.60-1.72(m,6H)；HRMS[ESI]:calcd for C28H27N2O7([M+H]+),503.1818；found,503.1794.
化合物27的理化性质如下：
1)黄色固体，熔点85-87℃；收率47％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2932,2861,1732,1616,1441,1242,1097,810,723；1H NMR(500MHz,CDCl3)δ:8.03(s,1H),7.51(dd,J＝10.5,15.0Hz,1H),6.97-7.00(m,2H),6.90-6.94(m,2H),6.69-6.86(m,7H),6.05(d,J＝15.5Hz,1H),5.99-6.00(m,4H),3.75-3.79(m,2H),3.35-3.38(m,2H),1.61-1.71(m,6H)；HRMS[ESI]:calcd for C30H28N2NaO7([M+Na]+),551.1794；found,551.1768.
化合物28的理化性质如下：
1)黄色固体，熔点101-103℃；收率58％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):3065,2931,2861,1738,1616,1253,1181,815,748；1H NMR(500MHz,CDCl3)δ:8.12(s,1H),7.57-7.60(m,2H),6.98(s,1H),6.90-6.92(m,2H),6.71-6.83(m,4H),5.99(s,2H),4.28(d,J＝16.0Hz,4H),3.73-3.81(m,2H),3.36-3.41(m,2H),1.61-1.72(m,6H)；HRMS[ESI]:calcd for C27H26N2NaO7([M+Na]+),513.1638；found,513.1583.
化合物29的理化性质如下：
1)黄色固体，熔点175-177℃；收率28％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2930,2858,1736,1624,1245,1106,803,724；1H NMR(500MHz,CDCl3)δ:8.05(s,1H),7.67(d,J＝16.0Hz,1H),6.98-7.07(m,3H),6.71-6.92(m,6H),6.38(d,J＝16.0Hz,1H),5.98-600(m,2H),4.27(d,J＝6.5Hz,4H),3.72-3.81(m,2H),3.35-3.39(m,2H),1.60-1.73(m,6H)；HRMS[ESI]:calcd for C29H28N2NaO7([M+Na]+),539.1794；found,539.1771.
化合物30的理化性质如下：
1)黄色固体，熔点95-97℃；收率47％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):3062,2919,2853,1772,1612,1445,1256,1111,810,718；1HNMR(500MHz,CDCl3)δ:8.03(s,1H),7.50-7.55(m,1H),6.96-6.99(m,3H),6.89(d,J＝8.0Hz,1H),6.69-6.85(m,7H),5.98-6.06(m,3H),4.27(s,4H),3.75-3.79(m,2H),3.34-3.38(m,2H),1.60-1.71(m,6H)；HRMS[ESI]:calcd for C31H30N2NaO7([M+Na]+),565.1951；found,565.1913.
化合物31的理化性质如下：
1)黄色固体，熔点135-137℃；收率49％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2930,2858,1760,1631,1442,1239,1127,807,717；1H NMR(500MHz,CDCl3)δ:8.12(s,1H),7.79(d,J＝7.5Hz,1H),7.43-7.48(m,2H),7.33-7.36(m,1H),6.98(s,1H),6.91(d,J＝8.0Hz,1H),6.72-6.82(m,4H),5.99(s,2H),3.75-3.78(m,2H),3.38-3.41(m,2H),1.63-1.71(m,6H)；HRMS[ESI]:calcd for C25H23ClN2NaO5([M+Na]+),489.1193；found,489.1165.
化合物32的理化性质如下：
1)黄色固体，熔点172-174℃；收率53％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2935,2858,1742,1625,1442,1238,1126,797,661；1H NMR(500MHz,CDCl3)δ:8.17(s,1H),8.03(s,1H),7.94-7.95(m,1H),7.55(dd,J＝3.0,8.0Hz,1H),7.40(t,J＝8.0Hz,1H),6.98(d,J＝1.5Hz,1H),6.91(dd,J＝1.5,8.0Hz,1H),6.74-6.83(m,4H),5.99(s,2H),3.76-3.81(m,2H),3.37-3.41(m,2H),1.60-1.73(m,6H)；HRMS[ESI]:calcdfor C25H23ClN2NaO5([M+Na]+),489.1193；found,489.1174.
化合物33的理化性质如下：
1)黄色固体，熔点196-198℃；收率47％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2938,2858,1761,1616,1444,1251,1126,808,760；1H NMR(500MHz,CDCl3)δ:8.09(s,1H),7.76(dd,J＝1.5,8.0Hz,1H),7.48-7.51(m,1H),6.98-7.01(m,3H),6.90(dd,J＝1.5,8.0Hz,1H),6.69-6.82(m,4H),5.99(s,2H),3.90(s,3H),3.74-3.77(m,2H),3.37-4.40(m,2H),1.64-1.68(m,6H)；HRMS[ESI]:calcd for C26H26N2NaO6([M+Na]+),485.1689；found,485.1670.
化合物34的理化性质如下：
1)黄色固体，熔点158-160℃；收率52％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2935,2858,1739,1634,1441,1241,1215,1126,791,735；1HNMR(500MHz,CDCl3)δ:8.16(s,1H),7.64(d,J＝8.0Hz,1H),7.58(s,1H),7.35(t,J＝8.0Hz,1H),7.12(dd,J＝2.5,6.5Hz,1H),6.98(s,1H),6.82(d,J＝5.5Hz,1H),6.72-6.79(m,4H),5.99(s,2H),3.78-3.86(m,5H),3.38-3.42(m,2H),1.64-1.73(m,6H)；HRMS[ESI]:calcdfor C26H26N2NaO6([M+Na]+),485.1689；found,485.1673.
化合物35的理化性质如下：
1)白色固体，熔点148-150℃；收率72％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2932,2857,1744,1632,1447,1244,1175,1060,804,740；1HNMR(500MHz,CDCl3)δ:8.17(s,1H),7.99(d,J＝8.5Hz,2H),7.44(d,J＝8.5Hz,2H),7.37(d,J＝8.5Hz,2H),7.31(d,J＝8.5Hz,2H),6.90-6.95(m,1H),6.82-6.85(m,1H),6.75(d,J＝11.0Hz,1H),3.76-3.82(m,2H),3.37-3.41(m,2H),1.52-1.72(m,6H)；HRMS[ESI]:calcdfor C24H22Cl2N2NaO3([M+Na]+),479.0905；found,479.0877.
化合物36的理化性质如下：
1)淡黄色固体，熔点195-197℃；收率58％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2936,2857,1737,1621,1446,1251,1128,1101,805,751；1HNMR(500MHz,CDCl3)δ:8.07(s,1H),7.70(d,J＝15.5Hz,1H),7.37(d,J＝8.5Hz,2H),7.31(d,J＝8.5Hz,2H),7.02-7.05(m,2H),6.88-6.94(m,1H),6.80-6.83(m,2H),6.72(d,J＝11.5Hz,1H),6.35(d,J＝16.0Hz,1H),6.02(s,2H),3.74-3.81(m,2H),3.34-3.39(m,2H),1.61-1.68(m,6H)；HRMS[ESI]:calcd for C27H25ClN2NaO5([M+Na]+),515.1350；found,515.1318.
化合物37的理化性质如下：
1)淡黄色固体，熔点85-87℃；收率66％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2927,2856,1767,1630,1454,1241,1136,1095,811,726；1HNMR(400MHz,CDCl3)δ:7.98(s,1H),7.36(d,J＝8.4Hz,2H),7.30(d,J＝8.8Hz,2H),6.86-6.92(m,1H),6.78(d,J＝15.2Hz,1H),6.68(d,J＝10.8Hz,1H),3.73-3.78(m,2H),3.32-3.35(m,2H),2.40(t,J＝7.6Hz,2H),1.59-1.67(m,8H),1.25-1.33(m,20H),0.86(t,J＝6.8Hz,3H)；HRMS[ESI]:calcd for C31H45ClN2NaO3([M+Na]+),551.3016；found,551.2987.
化合物38的理化性质如下：
1)淡黄色固体，熔点165-167℃；收率65％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2934,2854,1743,1631,1445,1250,1126,815,719；1H NMR(500MHz,CDCl3)δ:8.16(s,1H),7.99(d,J＝8.5Hz,2H),7.39-7.45(m,4H),6.75-6.89(m,5H),3.78-3.84(m,5H),3.38-3.42(m,2H),1.63-1.72(m,6H)；HRMS[ESI]:calcd for C25H25ClN2NaO4([M+Na]+),475.1401；found,475.1389.
化合物39的理化性质如下：
1)淡黄色固体，熔点134-136℃；收率60％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2937,2850,1734,1633,1444,1247,1105,800,722；1H NMR(500MHz,CDCl3)δ:8.05(s,1H),7.69(d,J＝15.5Hz,1H),7.39(d,J＝9.0Hz,2H),7.02-7.05(m,2H),6.81-6.93(m,5H),6.71-6.73(m,1H),6.36(d,J＝16.0Hz,1H),6.01(s,2H),3.78-3.84(m,5H),3.36-3.39(m,2H),1.61-1.72(m,6H)；HRMS[ESI]:calcd for C28H28N2NaO6([M+Na]+),511.1845；found,511.1823.
化合物40的理化性质如下：
1)黄色液体；收率51％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2926,2854,1765,1632,1454,1252,1101,818,724；1H NMR(400MHz,CDCl3)δ:7.97(s,1H),7.38(d,J＝8.8Hz,2H),6.84-6.92(m,2H),6.74-6.81(m,2H),6.68(dd,J＝2.8,8.4Hz,1H),3.73-3.82(m,5H),3.34-3.36(m,2H),2.39-2.44(m,2H),1.58-1.70(m,8H),1.25-1.33(m,20H),0.86(t,J＝6.8Hz,3H)；HRMS[ESI]:calcd forC32H48N2NaO4([M+Na]+),547.3512；found,547.3466.
化合物41的理化性质如下：
1)黄色固体，熔点186-188℃；收率48％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):3037,2932,2861,1729,1623,1447,1251,1063,812,731；1HNMR(500MHz,CDCl3)δ:8.15(s,1H),7.99(d,J＝8.5Hz,2H),7.43(d,J＝8.5Hz,2H),6.95-6.98(m,2H),6.73-6.84(m,4H),4.27-4.28(m,4H),3.74-3.80(m,2H),3.37-3.41(m,2H),1.66-1.72(m,6H)；HRMS[ESI]:calcd for C26H25ClN2NaO5([M+Na]+),503.1350；found,503.1339.
化合物42的理化性质如下：
1)黄色固体，熔点205-207℃；收率44％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2926,2859,1734,1627,1445,1248,1124,801,727；1H NMR(500MHz,CDCl3)δ:8.05(s,1H),7.69(d,J＝16.0Hz,1H),7.02-7.05(m,2H),6.94-6.98(m,2H),6.81-6.84(m,2H),6.70-6.79(m,3H),6.36(d,J＝16.0Hz,1H),6.01(s,2H),4.25-4.28(m,4H),3.74-3.80(m,2H),3.34-3.39(m,2H),1.60-1.71(m,6H)；HRMS[ESI]:calcd forC29H28N2NaO7([M+Na]+),539.1794；found,539.1768.
化合物43的理化性质如下：
1)黄色液体；收率31％；
2)该化合物的红外光谱图、核磁共振谱图特征：
IR cm-1(KBr):2926,2856,1764,1633,1454,1251,1105,810,728；1H NMR(500MHz,CDCl3)δ:7.96(s,1H),6.93-6.97(m,2H),6.66-6.83(m,4H),4.25-4.28(m,4H),3.72-3.77(m,2H),3.32-3.35(m,2H),2.41(t,J＝6.5Hz,2H),1.57-1.69(m,8H),1.25-1.34(m,20H),0.86(t,J＝7.5Hz,3H)；HRMS[ESI]:calcd for C33H48N2NaO5([M+Na]+),575.3461；found,575.3433.
实施例2：朱砂叶螨生测实验：
1、供试昆虫：朱砂叶螨(Tetranychus cinnabarinus Bois.)，由本实验室传代饲养。农业害螨具有个体小、繁殖快、适应性强及容易产生抗药性等特点【InsectBiochemistry and Molecular Biology,2020,120:103347】，该实施例以朱砂叶螨为代表，叶螨是农业害螨中最大的类群；而朱砂叶螨是一种代表性害螨，主要在叶背吸食汁液，使寄主组织造成机械损伤造成为害，在我国多地均有发生【Plant Protection,2005,2:90-91】。
2、样品及试剂：
样品为：98.32％螺螨酯原药(陕西美邦农药有限公司提供)(阳性对照)，胡椒碱类化合物(a-d)，及实施例1制备的中间体(e-l)和化合物1-43，丙酮(溶剂，成都市科龙化工试剂厂，分析纯)、吐温-80和蒸馏水。
3、生测方法：采用FAO推荐的玻片浸渍法：
①0.1‰吐温80母液配制：称取25mg吐温80溶于5mL丙酮溶液中，用蒸馏水定溶至250mL待用。
②初筛药液配制：分别称取3.0mg供试化合物，用120微升丙酮(目标体积的2％)溶解，再用配好的0.1‰吐温80定容至6.0mL，即配置成500mg/L药液，供初筛使用。
③供试螨的准备：将1cm宽的双面胶的贴在载玻片的一端，用0号毛笔挑选健康活泼、螨龄一致的朱砂叶螨雌成螨，小心整齐地将其背部粘在双面胶上，每块玻片粘35头左右，排成2行，将粘有供试螨的玻片放在垫有湿润海绵的铁盘中，并将铁盘置于26±1℃、相对湿度60％～80％、光照L:D＝14h:10h条件下的光照培养箱中，放置4小时后，用体视显微镜检查，剔除死亡和不活泼的个体，记录每块玻片上的活螨数量。
④浸药：将载玻片粘有螨的一端在供试药液中振荡浸渍5s后取出，用小滤纸条小心吸去多余药液(注意不能触碰到螨体)后放回铁盘，置于相同饲养条件下光照培养箱中，一块玻片为一个处理，每处理重复3次，以0.1‰吐温80溶液为空白对照。
⑤结果统计：浸药处理24小时后将玻片取出在体视显微镜下检查结果，检查时用毛笔尖轻触螨体，以其螯肢不动者为死亡，记录死亡个体数；连续观察记录72小时。根据下列公式计算供试螨48小时和72小时的死亡率(％)及校正死亡率(％)。
表1.本发明胡椒碱及胡椒碱类似物(a-d)，中间体(e-l)其化合物(1-43)的杀螨活性
结论：结果说明，上述大部分胡椒碱肟酯类衍生物72h杀螨活性较胡椒碱有显著提高，且化合物(6、16、26)72h杀螨活性与阳性对照螺螨酯相当，故有望用于制备高效、环保、低毒的植物源杀螨剂。
实施例3：苹果黄蚜生测实验
采用FAO推荐的微量点滴法
1.用丙酮将供试化合物配制成浓度为1mg/mL的溶液备用，以丙酮作为空白对照。
2.将挑好的蚜虫(大小一致、健康的无翅成蚜)在虫体腹部点滴0.043μL供试药液，然后将试虫转入直径为9cm的底部垫有滤纸保湿的培养皿中，每皿30头，每个培养皿为一个重复，每个处理重复3次，饲喂新鲜叶片，用湿脱脂棉缠住叶柄处，然后用纱布(或卫生纸)覆盖，置于光周期L:D＝14h:10h、温度(25±1)℃、相对湿度(50±7)％条件下饲养。
3.分别于24h、48h后观察并记录试虫的死亡情况，蚜虫的死亡判断以毛笔触及足和触角时完全不动为死亡。根据下列公式计算试虫24h和48h的死亡率(％)及校正死亡率(％)。
表2.本发明胡椒碱(a)、中间体(e，i)及其衍生物1-30在0.043μg/头剂量下对苹果黄蚜无翅成蚜的杀蚜虫活性
a Values are mean±SE of three replicates.
结论：结果表明，部分胡椒碱肟酯类衍生物(4，15，18，25)对苹果黄蚜具有较好的杀虫活性，48h校正死亡率在48.3％-66.3％，与胡椒碱相比活性得到显著提高。有望用于制备环保、低毒的植物源杀虫剂。
Claims (10)
1.一种胡椒碱肟酯类衍生物，其特征在于，该化合物的通式如下式所示：
其中：
R1选自氢，且R2选自氯；
或R1选自氢，且R2选自甲氧基；
或R1R2选自二氧亚甲基；
或R1R2选自二氧亚乙基；
R3选自烷基、取代或非取代苯基、取代或非取代肉桂基、5-(取代或非取代苯基)-2,4-戊二烯基的一种。
2.如权利要求1所述的胡椒碱肟酯类衍生物，其特征在于，所述的胡椒碱肟酯类衍生物具有以下结构之一：
(1):R1R2＝二氧亚甲基；R3＝CH3；
(2):R1R2＝二氧亚甲基；R3＝CH2CH3；
(3):R1R2＝二氧亚甲基；R3＝(CH2)4CH3；
(4):R1R2＝二氧亚甲基；R3＝(CH2)10CH3；
(5):R1R2＝二氧亚甲基；R3＝(CH2)11CH3；
(6):R1R2＝二氧亚甲基；R3＝(CH2)12CH3；
(7):R1R2＝二氧亚甲基；R3＝(CH2)13CH3；
(8):R1R2＝二氧亚甲基；R3＝(CH2)14CH3；
(9):R1R2＝二氧亚甲基；R3＝(CH2)16CH3；
(10):R1R2＝二氧亚甲基；R3＝苯基；
(11):R1R2＝二氧亚甲基；R3＝肉桂基；
(12):R1 R2＝二氧亚甲基；R3＝5-苯基-2,4-戊二烯基；
(13):R1R2＝二氧亚甲基；R3＝对氟苯基；
(14):R1R2＝二氧亚甲基；R3＝对氟肉桂基；
(15):R1R2＝二氧亚甲基；R3＝5-(对氟苯基)-2,4-戊二烯基；
(16):R1R2＝二氧亚甲基；R3＝对氯苯基；
(17):R1R2＝二氧亚甲基；R3＝对氯肉桂基；
(18):R1R2＝二氧亚甲基；R3＝5-(对氯苯基)-2,4-戊二烯基；
(19):R1R2＝二氧亚甲基；R3＝对甲基苯基；
(20):R1R2＝二氧亚甲基；R3＝对甲基肉桂基；
(21):R1R2＝二氧亚甲基；R3＝5-(对甲基苯基)-2,4-戊二烯基；
(22):R1R2＝二氧亚甲基；R3＝对甲氧基苯基；
(23):R1R2＝二氧亚甲基；R3＝对甲氧基肉桂基；
(24):R1R2＝二氧亚甲基；R3＝5-(对甲氧基苯基)-2,4-戊二烯基；
(25):R1R2＝二氧亚甲基；R3＝3,4-(二氧亚甲基)苯基；
(26):R1R2＝二氧亚甲基；R3＝3,4-(二氧亚甲基)肉桂基；
(27):R1R2＝二氧亚甲基；R3＝5-(3,4-(二氧亚甲基)苯基)-2,4-戊二烯基；
(28):R1R2＝二氧亚甲基；R3＝3,4-(二氧亚乙基)苯基；
(29):R1R2＝二氧亚甲基；R3＝3,4-(二氧亚乙基)肉桂基；
(30):R1R2＝二氧亚甲基；R3＝5-(3,4-(二氧亚乙基)苯基)-2,4-戊二烯基；
(31):R1R2＝二氧亚甲基；R3＝邻氯苯基；
(32):R1R2＝二氧亚甲基；R3＝间氯苯基；
(33):R1R2＝二氧亚甲基；R3＝邻甲氧基苯基；
(34):R1R2＝二氧亚甲基；R3＝间甲氧基苯基；
(35):R1＝H；R2＝氯；R3＝对氯苯基；
(36):R1＝H；R2＝氯；R3＝3,4-(二氧亚甲基)肉桂基；
(37):R1＝H；R2＝氯；R3＝(CH2)12CH3；
(38):R1＝H；R2＝甲氧基；R3＝对氯苯基；
(39):R1＝H；R2＝甲氧基；R3＝3,4-(二氧亚甲基)肉桂基；
(40):R1＝H；R2＝甲氧基；R3＝(CH2)12CH3；
(41):R1R2＝二氧亚乙基；R3＝对氯苯基；
(42):R1R2＝二氧亚乙基；R3＝3,4-(二氧亚甲基)肉桂基；
(43):R1R2＝二氧亚乙基；R3＝(CH2)12CH3。
3.一种胡椒碱肟酯类衍生物的制备方法，其特征在于，包括如下步骤：
步骤一：以下式所示胡椒碱类化合物为原料，
与三氯氧磷反应制得中间体，所述中间体结构式如下式所示：
其中，R1选自氢，且R2选自氯；或R1选自氢，且R2选自甲氧基；或R1R2选自二氧亚甲基；或R1R2选自二氧亚乙基；
步骤二：中间体与盐酸羟胺反应，得到肟类中间体，所述肟类中间体结构式如下式所示：
步骤三：肟类中间体与R3COOH反应，得到胡椒碱肟酯类衍生物，R3选自烷基、取代或非取代苯基、取代或非取代肉桂基、5-(取代或非取代苯基)-2,4-戊二烯基。
4.如权利要求3所述的胡椒碱肟酯类衍生物的制备方法，其特征在于，步骤一中的反应在N,N-二甲基甲酰胺(DMF)溶液中进行，反应温度为0-90℃。
5.如权利要求3所述的胡椒碱肟酯类衍生物的制备方法，其特征在于，步骤二中的反应在乙醇溶液中进行，同时加入盐酸羟胺和氢氧化钠，反应温度20-30℃。
6.如权利要求3所述的胡椒碱肟酯类衍生物的制备方法，其特征在于，步骤三中的R3COOH选自乙酸、丙酸、己酸、十二酸、十三酸、十四酸、十五酸、十六酸、十八酸、苯甲酸、肉桂酸、5-苯基-2,4-戊二烯基酸、对氟苯甲酸、对氟肉桂酸、5-(4-氟苯基)-2,4-戊二烯基酸、邻氯苯甲酸、间氯苯甲酸、对氯苯甲酸、对氯肉桂酸、5-(4-氯苯基)-2,4-戊二烯基酸、对甲基苯甲酸、对甲基肉桂酸、5-(4-甲基苯基)-2,4-戊二烯基酸、邻甲氧基苯甲酸、间甲氧基苯甲酸、对甲氧基苯甲酸、对甲氧基肉桂酸、5-(4-甲氧基苯基)-2,4-戊二烯基酸、胡椒酸、3,4-(二氧亚甲基)肉桂基酸、5-(3,4-(二氧亚甲基)苯基)-2,4-戊二烯基酸、3,4-二氧亚乙基苯甲酸、3,4-(二氧亚乙基)肉桂基酸、5-(3,4-(二氧亚乙基)苯基)-2,4-戊二烯基酸的一种；
步骤三的反应在无水二氯甲烷中进行，同时加入EDCI和DMAP，反应温度为20-30℃。
7.权利要求1或2所述的胡椒碱肟酯类衍生物作为杀虫剂的应用。
8.权利要求1或2所述的胡椒碱肟酯类衍生物作为杀螨剂的应用。
9.权利要求3～6任一权利要求所述的胡椒碱肟酯类衍生物的制备方法制备的胡椒碱肟酯类衍生物作为杀虫剂的应用。
10.权利要求3～6任一权利要求所述的胡椒碱肟酯类衍生物的制备方法制备的胡椒碱肟酯类衍生物作为杀螨剂的应用。
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