CN110903336B - Avermectin B 2a Oxime ether derivatives and application thereof in pesticides - Google Patents
Avermectin B 2a Oxime ether derivatives and application thereof in pesticides Download PDFInfo
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- CN110903336B CN110903336B CN201911323687.1A CN201911323687A CN110903336B CN 110903336 B CN110903336 B CN 110903336B CN 201911323687 A CN201911323687 A CN 201911323687A CN 110903336 B CN110903336 B CN 110903336B
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- avermectin
- oxime ether
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- 239000000575 pesticide Substances 0.000 title claims description 6
- -1 Avermectin B 2a Oxime ether derivatives Chemical class 0.000 title abstract description 9
- CWGATOJEFAKFBK-UHFFFAOYSA-N Ac-(E)-8-Tridecen-1-ol Natural products C1C(O)C(C)C(C(C)CC)OC11OC(CC=C(C)C(OC2OC(C)C(OC3OC(C)C(O)C(OC)C3)C(OC)C2)C(C)C=CC=C2C3(C(C(=O)O4)C=C(C)C(O)C3OC2)O)CC4C1 CWGATOJEFAKFBK-UHFFFAOYSA-N 0.000 title 1
- SHURRSUZDBDBMX-JLSLGBNPSA-N avermectin B2a Natural products CC[C@H](C)[C@H]1O[C@@]2(C[C@@H]3C[C@@H](CC=C(/C)[C@@H](O[C@H]4C[C@H](OC)[C@@H](O[C@H]5C[C@H](OC)[C@@H](O)[C@H](C)O5)[C@H](C)O4)[C@@H](C)C=CC=C6/OC[C@@H]7[C@H](O)C(=C[C@@H](C(=O)O3)[C@]67O)C)O2)C[C@@H](O)[C@@H]1C SHURRSUZDBDBMX-JLSLGBNPSA-N 0.000 title 1
- 230000000895 acaricidal effect Effects 0.000 claims abstract description 17
- CWGATOJEFAKFBK-PDVFGPFMSA-N 5-o-demethyl-22,23-dihydro-23-hydroxy-(13r,23s)-avermectin a1a Chemical compound C1[C@H](O)[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 CWGATOJEFAKFBK-PDVFGPFMSA-N 0.000 claims abstract description 9
- SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical class ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 claims abstract 8
- 230000002147 killing effect Effects 0.000 claims description 16
- 239000000642 acaricide Substances 0.000 claims description 11
- 241000238876 Acari Species 0.000 claims description 10
- 239000002917 insecticide Substances 0.000 claims description 10
- 241000500437 Plutella xylostella Species 0.000 claims description 6
- 235000013601 eggs Nutrition 0.000 claims description 6
- 241000238631 Hexapoda Species 0.000 claims description 4
- 241000344246 Tetranychus cinnabarinus Species 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 239000005660 Abamectin Substances 0.000 abstract description 26
- RRZXIRBKKLTSOM-XPNPUAGNSA-N avermectin B1a Chemical compound C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 RRZXIRBKKLTSOM-XPNPUAGNSA-N 0.000 abstract description 26
- 238000012360 testing method Methods 0.000 abstract description 15
- 238000006243 chemical reaction Methods 0.000 abstract description 10
- 230000001069 nematicidal effect Effects 0.000 abstract description 9
- 230000000749 insecticidal effect Effects 0.000 abstract description 5
- 230000004071 biological effect Effects 0.000 abstract description 4
- 238000010511 deprotection reaction Methods 0.000 abstract description 3
- 238000007254 oxidation reaction Methods 0.000 abstract description 3
- 238000006146 oximation reaction Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 description 35
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 22
- 238000005481 NMR spectroscopy Methods 0.000 description 20
- 241000244206 Nematoda Species 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 238000004949 mass spectrometry Methods 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
- 241000500441 Plutellidae Species 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 239000005645 nematicide Substances 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 241001454295 Tetranychidae Species 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- ZXCUOCHXNYWBBG-ZQWQDMLBSA-N (1s,2s,3s,4s)-3,4-bis[2-methylpropyl-[(4-phenoxyphenyl)methyl]carbamoyl]cyclobutane-1,2-dicarboxylic acid Chemical compound O=C([C@H]1[C@@H]([C@@H]([C@H]1C(O)=O)C(O)=O)C(=O)N(CC(C)C)CC=1C=CC(OC=2C=CC=CC=2)=CC=1)N(CC(C)C)CC(C=C1)=CC=C1OC1=CC=CC=C1 ZXCUOCHXNYWBBG-ZQWQDMLBSA-N 0.000 description 1
- GNPHAOQLHRZODS-ZQWQDMLBSA-N (1s,2s,3s,4s)-3,4-bis[butyl-[(4-phenoxyphenyl)methyl]carbamoyl]cyclobutane-1,2-dicarboxylic acid Chemical compound O=C([C@H]1[C@@H]([C@@H]([C@H]1C(O)=O)C(O)=O)C(=O)N(CCCC)CC=1C=CC(OC=2C=CC=CC=2)=CC=1)N(CCCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 GNPHAOQLHRZODS-ZQWQDMLBSA-N 0.000 description 1
- AHZCYZMNFBGXAC-UHFFFAOYSA-N 1-[[5-chloro-2-(trifluoromethyl)phenyl]methyl]-7-(2-piperazin-1-ylpyridin-4-yl)-3,4-dihydro-2h-pyrido[2,3-b]pyrazine Chemical compound FC(F)(F)C1=CC=C(Cl)C=C1CN1C2=CC(C=3C=C(N=CC=3)N3CCNCC3)=CN=C2NCC1 AHZCYZMNFBGXAC-UHFFFAOYSA-N 0.000 description 1
- JGMXNNSYEFOBHQ-OWOJBTEDSA-N 2-[(e)-4-morpholin-4-ylbut-2-enyl]-1,1-dioxothieno[3,2-e]thiazine-6-sulfonamide Chemical compound O=S1(=O)C=2SC(S(=O)(=O)N)=CC=2C=CN1C\C=C\CN1CCOCC1 JGMXNNSYEFOBHQ-OWOJBTEDSA-N 0.000 description 1
- ORQHHLPTMSGMQT-UHFFFAOYSA-N 2-[4-(5-fluoropyridin-2-yl)piperazin-1-yl]-n-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)acetamide Chemical compound N1=CC(F)=CC=C1N1CCN(CC(=O)NC=2SC=3CCCCC=3N=2)CC1 ORQHHLPTMSGMQT-UHFFFAOYSA-N 0.000 description 1
- OVDGUTHABMXVMI-UHFFFAOYSA-N 3-nitro-4-(propylamino)benzoic acid Chemical compound CCCNC1=CC=C(C(O)=O)C=C1[N+]([O-])=O OVDGUTHABMXVMI-UHFFFAOYSA-N 0.000 description 1
- IBSREHMXUMOFBB-JFUDTMANSA-N 5u8924t11h Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O3)C=C[C@H](C)[C@@H](C(C)C)O4)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 IBSREHMXUMOFBB-JFUDTMANSA-N 0.000 description 1
- UFMQJYHLIUACCG-UHFFFAOYSA-N 8-nitroindolo[2,1-b]quinazoline-6,12-dione Chemical compound C1=CC=C2C(=O)N3C4=CC=C([N+](=O)[O-])C=C4C(=O)C3=NC2=C1 UFMQJYHLIUACCG-UHFFFAOYSA-N 0.000 description 1
- 240000007124 Brassica oleracea Species 0.000 description 1
- 235000003899 Brassica oleracea var acephala Nutrition 0.000 description 1
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 description 1
- 235000001169 Brassica oleracea var oleracea Nutrition 0.000 description 1
- 241000243770 Bursaphelenchus Species 0.000 description 1
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- TZYWCYJVHRLUCT-VABKMULXSA-N N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal Chemical compound CC(C)C[C@@H](C=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1 TZYWCYJVHRLUCT-VABKMULXSA-N 0.000 description 1
- TZCCKCLHNUSAMQ-DUGSHLAESA-N NC(=O)C[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc2ccc(F)cc2)NC(=O)[C@H](Cc3c[nH]c4ccccc34)NC(=O)Cc5cccs5)C(=O)N Chemical compound NC(=O)C[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc2ccc(F)cc2)NC(=O)[C@H](Cc3c[nH]c4ccccc34)NC(=O)Cc5cccs5)C(=O)N TZCCKCLHNUSAMQ-DUGSHLAESA-N 0.000 description 1
- AKQOBHZKBDHWQI-BZEFIUHZSA-N O[C@H]1C[C@@H](CCC1)N1C(C2(C3=C1N=C(N=C3)NC1=CC=C(C=C1)S(=O)(=O)NC([2H])([2H])[2H])CC2)=O Chemical compound O[C@H]1C[C@@H](CCC1)N1C(C2(C3=C1N=C(N=C3)NC1=CC=C(C=C1)S(=O)(=O)NC([2H])([2H])[2H])CC2)=O AKQOBHZKBDHWQI-BZEFIUHZSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 240000006677 Vicia faba Species 0.000 description 1
- 235000010749 Vicia faba Nutrition 0.000 description 1
- 235000002098 Vicia faba var. major Nutrition 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000003139 biocide Substances 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940127108 compound 5g Drugs 0.000 description 1
- 229940126136 compound 5i Drugs 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 239000004495 emulsifiable concentrate Substances 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 230000001418 larval effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000003120 macrolide antibiotic agent 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
- JBLLRCOZJMVOAE-HSQYWUDLSA-N n-[(2s)-1-[[(2s)-1-(1,3-benzothiazol-2-yl)-1-oxo-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-4-methoxy-1h-indole-2-carboxamide Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)C=1NC=2C=CC=C(C=2C=1)OC)C(=O)C=1SC2=CC=CC=C2N=1)[C@@H]1CCNC1=O JBLLRCOZJMVOAE-HSQYWUDLSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- CAEWJEXPFKNBQL-UHFFFAOYSA-N prop-2-enyl carbonochloridate Chemical compound ClC(=O)OCC=C CAEWJEXPFKNBQL-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000000273 veterinary drug Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
-
- 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
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Agronomy & Crop Science (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Dentistry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
Description
技术领域Technical Field
本发明涉及阿维菌素B2a肟醚类衍生物的合成方法及应用，特别是阿维菌素B2a肟醚类衍生物在杀虫、杀螨、杀线虫方面的用途。The invention relates to a synthesis method and application of avermectin B 2a oxime ether derivatives, in particular to the application of avermectin B 2a oxime ether derivatives in insecticide, acaricide and nematode killing.
背景技术Background Art
阿维菌素(Avermectin，简称AVM)作为农药和兽药应用在农业和畜牧业领域，是世界范围内用量最大的生物农药品种。AVM属于大环内酯类化合物，主要包括8个同系物。阿维菌素结构如式(Ⅱ)所示：Avermectin (AVM) is used as a pesticide and veterinary drug in agriculture and animal husbandry, and is the most widely used biological pesticide in the world. AVM belongs to the macrolide class of compounds, mainly including 8 homologues. The structure of Avermectin is shown in formula (II):
阿维菌素B1(AVM B1)作为杀虫剂和杀螨剂被先正达公司引入农药市场，其衍生物，甲氨基阿维菌素苯甲酸盐(简称甲维盐)也被广泛用于防治农田鳞翅目害虫。AVM B1在工业生产过程中，会产生废渣，废渣的产生增加能源消耗、造成环境污染，其主要成分是阿维菌素B2a(AVM B2a)。2012年，我国禁止在阿维菌素乳油中混合使用阿维菌素油膏。由于阿维菌素油膏毒性较高需要特殊处理且成本过高，成为限制阿维菌素行业发展的重要问题。Avermectin B 1 (AVM B 1 ) was introduced into the pesticide market by Syngenta as an insecticide and acaricide. Its derivative, avermectin benzoate (abbreviated as avermectin benzoate), is also widely used to control lepidopteran pests in farmland. AVM B 1 produces waste residues during the industrial production process, which increases energy consumption and causes environmental pollution. Its main component is avermectin B 2a (AVM B 2a ). In 2012, China banned the use of avermectin ointment mixed with avermectin emulsifiable concentrate. Due to the high toxicity of avermectin ointment, which requires special treatment and is too expensive, it has become an important issue restricting the development of the avermectin industry.
AVM B2a单独使用价值有限，采用化学转化方法，变成更有用的农用化学品对于阿维产业的健康发展是十分必要的。AVM B2a中存在4个羟基，其活性顺序依次为C5-OH、C23-OH、C4"-OH、C7-OH，关于AVM B2a的研究主要集中在5位和4″位，暂没有发现具有应用价值的新化合物。因此将衍生化位点聚焦在没有修饰改造过的C23-OH。参考AVM B1的结构改造规律，对其进行化学结构修饰，期待提高其生物活性。AVM B 2a has limited value when used alone. It is necessary to use chemical transformation methods to transform it into more useful agricultural chemicals for the healthy development of the AVM industry. There are 4 hydroxyl groups in AVM B 2a , and their activity order is C 5 -OH, C 23 -OH, C 4" -OH, and C 7 -OH. The research on AVM B 2a is mainly focused on the 5- and 4" positions, and no new compounds with application value have been found. Therefore, the derivatization site is focused on the unmodified C 23 -OH. Referring to the structural modification rules of AVM B 1 , it is chemically modified in the hope of improving its biological activity.
发明内容Summary of the invention
本发明的目的是提供了16种阿维菌素B2a肟醚类衍生物的合成方法以及在杀虫、杀螨、杀线虫方面的用途。以阿维菌素B2a为原料，使用羟基保护基试剂保护阿维菌素B2a的5位和4"位羟基，通过氧化反应、肟化反应和脱保护，合成得到阿维菌素B2a肟醚类化合物，并且对该类化合物进行杀虫、杀螨、杀线虫活性测试，其生物活性测试结果显示该类化合物具有良好的杀虫、杀螨、杀线虫活性，是一类结构新颖、未见文献报道、应用前景广阔的杀虫剂、杀螨剂和杀线虫剂。The purpose of the present invention is to provide a method for synthesizing 16 avermectin B 2a oxime ether derivatives and their uses in insecticide, acaricide and nematode killing. With avermectin B 2a as a raw material, a hydroxyl protecting group reagent is used to protect the 5-position and 4-position hydroxyl groups of avermectin B 2a , and avermectin B 2a oxime ether compounds are synthesized through oxidation reaction, oximation reaction and deprotection, and the insecticide, acaricide and nematode killing activity of the compounds are tested, and the biological activity test results show that the compounds have good insecticide, acaricide and nematode killing activities, and are a class of insecticides, acaricides and nematode killing agents with novel structures, no literature reports and broad application prospects.
本发明提供阿维菌素B2a肟醚类化合物的结构通式为(Ⅰ)。The invention provides an avermectin B 2a oxime ether compound having a general structural formula (Ⅰ).
其中：R1代表氢、甲基、乙基、苄基、三苯基甲基、
R2代表4-腈基、4-F、4-Br、4-CH3、4-C(CH3)3、4-O-CH3、4-CF3、2-Cl-6-Cl、R 2 represents 4-nitrile, 4-F, 4-Br, 4-CH 3 , 4-C(CH 3 ) 3 , 4-O-CH 3 , 4-CF 3 , 2-Cl-6-Cl,
2-F-6-F、2-F-6-Cl。2-F-6-F, 2-F-6-Cl.
本发明设计的化合物的制备方法是先使用羟基保护基试剂保护阿维菌素B2a的5位和4"位羟基，通过氧化反应、肟化反应和脱保护，合成得到阿维菌素B2a肟醚类化合物。The preparation method of the compound designed by the present invention is to first use a hydroxyl protecting group reagent to protect the 5-position and 4-position hydroxyl groups of avermectin B 2a , and then synthesize the avermectin B 2a oxime ether compound through oxidation reaction, oximation reaction and deprotection.
本发明涉及的化合物及其可以接受的盐在农业上用作杀虫剂、杀螨剂和杀线虫剂。The compounds and acceptable salts thereof of the present invention are used as insecticides, acaricides and nematicides in agriculture.
本发明涉及的化合物及其在农业上可以接受的盐还可以作为有效成分与其他成分混合作为农药复合物，用作杀虫剂、杀螨剂和杀线虫剂。The compound and its agriculturally acceptable salts can also be used as active ingredients and mixed with other ingredients to form a pesticide complex, and used as insecticide, acaricide and nematicide.
本发明提供了阿维菌素B2a肟醚类化合物，并且对该类化合物进行杀虫、杀螨、杀线虫活性测试，其生物活性测试结果显示该类化合物具有良好的杀虫、杀螨、杀线虫活性，是一类结构新颖、未见文献报道、应用前景广阔的杀虫剂、杀螨剂和杀线虫剂。The invention provides avermectin B 2a oxime ether compounds, and performs insecticidal, acaricidal and nematicidal activity tests on the compounds. The biological activity test results show that the compounds have good insecticidal, acaricidal and nematicidal activities, and are a class of insecticides, acaricides and nematicides with novel structures, no literature reports and broad application prospects.
具体实施方案：Specific implementation plan:
实施例1：Embodiment 1:
取15.00g AVM B2a和120mL二氯甲烷于250mL四口圆底烧瓶中，降温至0℃，分别将3.25g氯甲酸烯丙酯和3.95g四甲基乙二胺溶于5mL二氯甲烷，并将其缓慢滴加到反应体系中，0℃温度下反应8-12h，再缓慢滴加4.53g TMEDA的二氯甲烷稀释液，控温反应2h，反应完全后，加入50mL饱和碳酸氢钠溶液，再用3×20mL二氯甲烷萃取，收集二氯甲烷层，有机相用无水硫酸镁干燥后，减压浓缩，硅胶色谱柱纯化得到14.80g白色晶体状固体2，质谱分析结果TOF-MS:1081.320[M+Na]+，熔点107-116℃，产率83％。15.00 g AVM B 2a and 120 mL dichloromethane were placed in a 250 mL four-necked round-bottom flask and cooled to 0°C. 3.25 g allyl chloroformate and 3.95 g tetramethylethylenediamine were dissolved in 5 mL dichloromethane respectively and slowly added dropwise to the reaction system. The mixture was reacted at 0°C for 8-12 h. Then 4.53 g TMEDA diluted in dichloromethane was slowly added dropwise. The temperature was controlled and the reaction was carried out for 2 h. After the reaction was complete, 50 mL saturated sodium bicarbonate solution was added. The mixture was extracted with 3×20 mL dichloromethane. The dichloromethane layer was collected. The organic phase was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The mixture was purified by silica gel chromatography to obtain 14.80 g white crystalline solid 2. The mass spectrometry analysis results showed TOF-MS: 1081.320 [M+Na] + , melting point 107-116°C, and yield 83%.
核磁共振氢谱：1H NMR(CDCl3,δ/ppm,400MHz):5.83-5.93(m,2H,-CH2-CH＝CH2),5.77(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.65(dd,J＝16.0,12.0Hz,1H,-CH-CH＝C-C＝C-),5.50(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.30-5.32(m,4H,-CH＝CH2),5.30(d,J＝2.8Hz,1H,-C＝C-CH-OH),5.20(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH2-),4.90(d,J＝4.4Hz,1H,-CH-CH-O-),4.70(d,J＝4.0Hz,1H,-CH＝C-),4.61(s,2H,-CH2-),4.60-4.63(m,1H,-CH-O-C＝O-),4.59(s,2H,-CH2-),4.56(t,J＝3.2Hz,2H,-O-CH-CH2-),4.40(d,J＝16.0Hz,1H,-CH-),4.04(d,J＝12.0Hz,1H,-CH-),3.88(s,1H,-OH),3.80-3.85(m,1H,CH3-CH-),3.70(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.59-3.61(m,1H,-(CH2)2-CH-OH),3.54-3.57(m,1H,CH3-CH-),3.54-3.55(m,1H,CH3-CH-O-),3.47-3.54(m,1H,-CH-CH-CH2-),3.37(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.36(s,3H,-O-CH3),3.32(s,3H,-O-CH3),3.30-3.31(m,1H,-CH-CH-CH2-),3.30(d,J＝8.0Hz,1H,-C-CH-CH-),3.29(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),3.16(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.46(d,J＝3.6Hz,1H,-CH-CH-),2.16-2.23(m,2H,-C＝CH-CH2-CH-),1.90-2.23(m,2H,-CH-CH2-),1.75-2.15(m,4H,-CH-CH2-CH-),1.75-1.93(m,2H,-CH-CH2-CH-),1.68-1.72(m,1H,-CH-CH3),1.61-1.62(m,2H,-CH2-CH-OH),1.49-1.52(m,1H,CH3-CH-CH-),1.47-1.49(m,2H,-CH-CH2-CH3),1.19-1.34(m,6H,-CH3),0.88-1.19(m,12H,-CH3),0.76-0.85(m,6H,-CH3).Hydrogen nuclear magnetic resonance spectrum: 1 H NMR (CDCl 3 , δ/ppm, 400MHz): 5.83-5.93 (m, 2H, -CH 2 -CH＝CH 2 ), 5.77 (dd, J＝14.8, 12.4Hz, 1H, -C＝CH-C＝C),5.65(dd,J＝16.0,12.0Hz,1H,-CH-CH＝CC＝C-),5.50(dd,J＝14.4,9.6Hz,1H,-C＝ CH-C＝C),5.30-5.32(m,4H,-CH＝ CH2 ),5.30(d,J＝2.8Hz,1H,-C＝C-CH-OH),5.20(dd,J＝12.0 ,9.2Hz,1H,-C＝CH-CH 2 -),4.90(d,J＝4.4Hz,1H,-CH-CH-O-),4.70(d,J＝4.0Hz,1H,-CH＝C-),4.61(s,2H,-CH 2 -),4.60-4.63(m,1H,-CH-OC＝O-),4.59(s,2H,-CH 2 -),4.56(t,J＝3.2Hz,2H,-O-CH-CH 2 -),4.40(d,J＝16.0Hz,1H,-CH-),4.04(d,J＝12.0Hz,1H,-CH-),3.88(s,1H,-OH),3.80-3.85(m ,1H,CH 3 -CH-),3.70(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.59-3.61(m,1H,-(CH 2 ) 2 -CH-OH),3.54-3.57(m ,1H,CH 3 -CH-),3.54-3.55(m,1H,CH 3 -CH-O-),3.47-3.54(m,1H,-CH-CH-CH 2 -),3.37(dd,J ＝14.4,9.6Hz,1H,-CH-CH-CH-),3.36(s,3H,-O-CH 3 ),3.32(s,3H,-O-CH 3 ),3.30-3.31(m,1H ,-CH-CH-CH 2 -),3.30(d,J＝8.0Hz,1H,-C-CH-CH-),3.29(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),3.16(dd ,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.46(d,J＝3.6Hz,1H,-CH-CH-),2.16-2.23(m,2H,-C＝CH- CH 2 -CH-),1.90-2.23(m,2H,-CH-CH 2 -),1.75-2.15(m,4H,-CH-CH 2 -CH-),1.75-1.93(m,2H,- CH-CH 2 -CH-),1.68-1.72(m,1H,-CH-CH 3 ),1.61-1.62(m,2H,-CH 2 -CH-OH),1.49-1.52(m,1H,CH 3 -CH-CH-),1.47-1.49(m,2H,-CH-CH 2 - CH 3 ),1.19-1.34(m,6H,-CH 3 ),0.88-1.19(m,12H,-CH 3 ),0.76-0.85(m,6H,-CH 3 ).
取10.00g中间体2和50mL二氯甲烷于150mL四口圆底烧瓶中，在氮气保护下，加入8.10g戴斯马丁氧化剂，室温下反应2h，反应完成后，用50mL混合液(饱和碳酸氢钠溶液：饱和硫代硫酸钠溶液体积比为1：2)终止反应，再用二氯甲烷萃取、分液，有机相用无水硫酸镁干燥，减压浓缩，硅胶色谱柱纯化得到7.62g淡黄色固体3，质谱分析结果TOF-MS:1079.286[M+Na]+，熔点102-110℃，产率76％。10.00 g of intermediate 2 and 50 mL of dichloromethane were placed in a 150 mL four-necked round-bottom flask. Under nitrogen protection, 8.10 g of Dess-Martin oxidant was added. The reaction was allowed to react at room temperature for 2 h. After the reaction was completed, 50 mL of a mixed solution (saturated sodium bicarbonate solution: saturated sodium thiosulfate solution, volume ratio 1:2) was used to terminate the reaction. The mixture was extracted and separated with dichloromethane. The organic phase was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and purified by silica gel chromatography to obtain 7.62 g of a light yellow solid 3. Mass spectrometry analysis results: TOF-MS: 1079.286 [M+Na] + , melting point 102-110°C, yield 76%.
核磁共振氢谱：1H NMR(CDCl3,δ/ppm,400MHz):5.85-5.91(m,2H,-CH2-CH＝CH2),5.75(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.66(dd,J＝16.0,12.0Hz,1H,-CH-CH＝C-C＝C-),5.50(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.29-5.33(m,4H,-CH＝CH2),5.22(d,J＝2.8Hz,1H,-C＝C-CH-OH),5.19(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH2-),4.85(d,J＝4.4Hz,1H,-CH-CH-O-),4.68(d,J＝4.0Hz,1H,-CH＝C-),4.60-4.63(m,3H),4.59(s,2H,-CH2-),4.56(t,J＝3.2Hz,2H,-O-CH-CH2-),4.40(d,J＝16.0Hz,1H,-CH-),4.05(d,J＝12.0Hz,1H,-CH-),3.86(s,1H,-OH),3.73-3.84(m,2H),3.44-3.57(m,5H),3.36(s,3H,-O-CH3),3.32(s,3H,-O-CH3),3.29-3.31(m,3H),3.15(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.45(d,J＝3.6Hz,1H,-CH-CH-),2.13-2.41(m,7H),1.18-1.75(m,14H),0.92-1.18(m,12H,-CH3),0.90-0.92(m,6H,-CH3).Hydrogen nuclear magnetic resonance spectrum: 1 H NMR (CDCl 3 , δ/ppm, 400MHz): 5.85-5.91 (m, 2H, -CH 2 -CH＝CH 2 ), 5.75 (dd, J＝14.8, 12.4Hz, 1H, -C＝CH-C＝C),5.66(dd,J＝16.0,12.0Hz,1H,-CH-CH＝CC＝C-),5.50(dd,J＝14.4,9.6Hz,1H,-C＝ CH-C＝C),5.29-5.33(m,4H,-CH＝ CH2 ),5.22(d,J＝2.8Hz,1H,-C＝C-CH-OH),5.19(dd,J＝12.0 ,9.2Hz,1H,-C＝CH-CH 2 -),4.85(d,J＝4.4Hz,1H,-CH-CH-O-),4.68(d,J＝4.0Hz,1H,-CH＝C-),4.60-4.63(m,3H), 4.59(s,2H,-CH 2 -),4.56(t,J＝3.2Hz,2H,-O-CH-CH 2 -),4.40(d,J＝16.0Hz,1H,-CH-),4.05 (d,J＝12.0Hz,1H,-CH-),3.86(s,1H,-OH),3.73-3.84(m,2H),3.44-3.57(m,5H),3.36(s,3H,- O-CH 3 ),3.32(s,3H,-O-CH 3 ),3.29-3.31(m,3H),3.15(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.45(d,J＝3.6Hz,1H,-CH-CH-) ,2.13-2.41(m,7H),1.18-1.75(m,14H),0.92-1.18(m,12H,-CH 3 ),0.90-0.92(m,6H,-CH 3 ).
取23.75g中间体3于1000mL三口圆底烧瓶中，将其用400mL无水乙醇溶解，冰水降温至0℃，加入25mL吡啶和10.38g盐酸羟胺，0℃下反应2h，用摩尔浓度为3mol/L的HCl调pH至3～4时析出大量白色固体，减压抽滤得到粗产物，自然晾干后用硅胶色谱柱纯化得到18.3g白色中间体4a，质谱分析结果TOF-MS:1094.520[M+Na]+，熔点108-112℃，产率76％。23.75 g of intermediate 3 was placed in a 1000 mL three-necked round-bottom flask, dissolved in 400 mL of anhydrous ethanol, cooled to 0°C with ice water, and added with 25 mL of pyridine and 10.38 g of hydroxylamine hydrochloride. The mixture was reacted at 0°C for 2 h. When the pH was adjusted to 3-4 with 3 mol/L HCl, a large amount of white solid precipitated. The crude product was filtered off under reduced pressure and naturally dried. After purification using a silica gel column, 18.3 g of white intermediate 4a was obtained. The mass spectrometry analysis results showed TOF-MS: 1094.520 [M+Na] + , melting point 108-112°C, and yield 76%.
核磁共振氢谱：1H NMR(DMSO-d6δ/ppm,400MHz):10.46(s,1H,-OH),5.88-5.98(m,2H,-CH2-CH＝CH2),5.78(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.66(dd,J＝16.0,12.0Hz,1H,-CH-CH＝C-C＝C-),5.54(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.30-5.36(m,4H,-CH＝CH2),5.27(d,J＝2.8Hz,1H,-C＝C-CH-OH),5.24(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH2-),4.80(d,J＝4.4Hz,1H,-CH-CH-O-),4.71(d,J＝4.0Hz,1H,-CH＝C-),4.62-4.63(m,3H),4.57(s,2H,-CH2-),4.47(t,J＝3.2Hz,2H,-O-CH-CH2-),4.29(d,J＝16.0Hz,1H,-CH-),3.89(d,J＝12.0Hz,1H,-CH-),3.78(s,1H,-OH),3.56-3.76(m,2H),3.33-3.56(m,5H),3.31(s,3H,-O-CH3),3.26(s,3H,-O-CH3),3.16-3.19(m,3H),3.14(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.46(d,J＝3.6Hz,1H,-CH-CH-),1.80-2.50(m,7H),1.24-1.70(m,14H),0.95-1.18(m,12H,-CH3),0.89-0.94(m,6H,-CH3).Hydrogen nuclear magnetic resonance spectrum: 1 H NMR (DMSO-d 6 δ/ppm, 400MHz): 10.46 (s, 1H, -OH), 5.88-5.98 (m, 2H, -CH 2 -CH＝CH 2 ), 5.78 ( dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.66(dd,J＝16.0,12.0Hz,1H,-CH-CH＝CC＝C-),5.54(dd,J ＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.30-5.36(m,4H,-CH＝CH 2 ),5.27(d,J＝2.8Hz,1H,-C＝C-CH -OH), 5.24 (dd, J＝12.0, 9.2Hz, 1H, -C＝CH-CH 2 -),4.80(d,J＝4.4Hz,1H,-CH-CH-O-),4.71(d,J＝4.0Hz,1H,-CH＝C-),4.62-4.63(m,3H), 4.57(s,2H,-CH 2 -),4.47(t,J＝3.2Hz,2H,-O-CH-CH 2 -),4.29(d,J＝16.0Hz,1H,-CH-),3.89 (d,J＝12.0Hz,1H,-CH-),3.78(s,1H,-OH),3.56-3.76(m,2H),3.33-3.56(m,5H),3.31(s,3H,- O-CH 3 ),3.26(s,3H,-O-CH 3 ),3.16-3.19(m,3H),3.14(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.46(d,J＝3.6Hz,1H,-CH-CH-) ,1.80-2.50(m,7H),1.24-1.70(m,14H),0.95-1.18(m,12H,-CH 3 ),0.89-0.94(m,6H,-CH 3 ).
取0.97g中间体4a于100mL单口瓶中，用30mL的醋酸异丙酯和乙醇的混合溶液(体积比为7:3)溶解，降温至0℃，加入0.01g四(三苯基膦)钯，之后缓慢加入0.07g硼氢化钠，室温下敞口反应，反应完全后，加入10mL饱和碳酸氢钠溶液，用3×10mL二氯甲烷萃取产物，合并二氯甲烷层后用无水硫酸镁干燥，减压浓缩，硅胶柱色谱纯化得到0.51g淡黄色中间体5a，高分辨质谱分析结果HRMS:926.4878[M+Na]+，熔点136-144℃，产率62％。0.97 g of intermediate 4a was taken into a 100 mL single-mouth bottle, dissolved with 30 mL of a mixed solution of isopropyl acetate and ethanol (volume ratio of 7:3), cooled to 0°C, 0.01 g of tetrakis(triphenylphosphine)palladium was added, and then 0.07 g of sodium borohydride was slowly added. The reaction was carried out in an open state at room temperature. After the reaction was complete, 10 mL of saturated sodium bicarbonate solution was added, and the product was extracted with 3×10 mL of dichloromethane. The dichloromethane layers were combined and dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain 0.51 g of light yellow intermediate 5a. High-resolution mass spectrometry analysis results HRMS: 926.4878 [M+Na] + , melting point 136-144°C, and yield 62%.
核磁共振氢谱：1H NMR(DMSO-d6,δ/ppm,400MHz):10.46(s,1H,-OH),5.87(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.75(dd,J＝16.0,12.0Hz,1.H,-CH-CH＝C-C＝C-),5.61(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.34(s,1H,-OH),5.24(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH2-),5.10(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),4.73-4.84(m,1H,-CH-O-C＝O-),4.70(t,J＝3.2Hz,2H,-O-CH-CH2-),4.58(d,J＝16.0Hz,1H,-CH-),4.45(d,J＝12.0Hz,1H,-CH-),4.07(s,1H,-OH),4.00-4.06(m,1H,CH3-CH-),3.90(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.75(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.61(d,J＝4.4Hz,1H,-CH-CH-O-),3.54-3.57(m,1H,CH3-CH-),3.54-3.55(m,1H,CH3-CH-O-),3.47-3.54(m,1H,-CH-CH-CH2-),3.37(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.32(s,3H,-O-CH3),3.31(s,3H,-O-CH3),3.23-3.27(m,1H,-CH-CH-CH2-),3.17(d,J＝8.0Hz,1H,-C-CH-CH-),3.08(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.89(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.71(m,1H,-CH-CH3),2.50(d,J＝3.6Hz,1H,-CH-CH-),2.34-2.61(m,2H,-CH2-C＝N-),2.21-2.32(m,2H,-C＝CH-CH2-CH-),1.86-2.21(m,2H,-CH-CH2-),1.72-2.18(m,4H,-CH-CH2-CH-),1.72-1.99(m,2H,-CH-CH2-CH-),1.60-1.63(m,1H,CH3-CH-CH-),1.51-1.54(m,2H,-CH-CH2-CH3),1.30-1.47(m,6H,-CH3),1.02-1.30(m,12H,-CH3),0.89-0.95(m,6H,-CH3).H NMR: 1 H NMR (DMSO-d 6 ,δ/ppm,400MHz):10.46(s,1H,-OH),5.87(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.75(dd,J＝16.0,12.0Hz,1.H,-CH-CH＝CC＝C-),5.61(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.34(s,1H,-OH),5.24(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH 2 -),5.10(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),4.73-4.84(m,1H,-CH-OC＝O-),4.70(t,J＝3.2Hz,2H,-O-CH-CH 2 -),4.58(d,J＝16.0Hz,1H,-CH-),4.45(d, J＝12.0Hz,1H,-CH-),4.07(s,1H,-OH),4.00-4.06(m,1H,CH 3 -CH-),3.90(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.75(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.61(d,J＝4.4Hz,1H,-CH-CH-O-),3.54-3.57(m,1H,CH 3 -CH-),3.54-3.55(m,1H ,CH 3 -CH-O-),3.47-3.54(m,1H,-CH-CH-CH 2 -),3.37(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.32(s,3H,-O-CH 3 ),3.31(s,3H,-O-CH 3 ),3.23-3.27(m,1H,-CH-CH- CH 2 -),3.17(d,J＝8.0Hz,1H,-C-CH-CH-),3.08(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.89(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.71(m,1H,-CH-CH 3 ),2.50(d,J＝ 3.6Hz,1H,-CH-CH-),2.34-2.61(m,2H,-CH 2 -C＝N-),2.21-2.32(m,2H,-C＝CH-CH 2 -CH-),1.86-2.21(m,2H,-CH-CH 2 -),1.72-2.18(m,4H,-CH-CH 2 -CH-),1.72-1.99(m,2H,-CH-CH 2 -CH-),1.60-1.63(m,1H,CH 3 -CH-CH-),1.51-1.54(m,2H,-CH-CH 2 -CH 3 ),1.30-1.47(m,6H,-CH 3 ),1.02-1.30(m,12H,-CH 3 ),0.89-0.95(m,6H,-CH 3 ).
化合物5b～5p按照与5a相似的方法合成，相关理化数据列于表1中。Compounds 5b-5p were synthesized in a similar manner to 5a, and their relevant physicochemical data are listed in Table 1.
表1目标化合物5b～5p的理化参数及质谱数据Table 1 Physicochemical parameters and mass spectrometry data of target compounds 5b～5p
核磁共振氢谱：H NMR spectrum:
化合物5b：1H NMR(DMSO-d6,δ/ppm,400MHz):5.87(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.74(dd,J＝16.0,12.0Hz,1H,-CH-CH＝C-C＝C-),5.62(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.33(s,1H,-OH),5.23(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH2-),5.10(br,1H,-OH),5.03(d,J＝4.0Hz,1H,-CH＝C-),4.73-4.85(m,1H,-CH-O-C＝O-),4.70(t,J＝3.2Hz,2H,-O-CH-CH2-),4.58(d,J＝16.0Hz,1H,-CH-),4.46(d,J＝12.0Hz,1H,-CH-),4.05(s,1H,-OH),4.01-4.04(m,1H,CH3-CH-),3.90(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.78(s,3H,-CH3),3.74(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.61(d,J＝4.4Hz,1H,-CH-CH-O-),3.54-3.58(m,1H,CH3-CH-),3.54-3.55(m,1H,CH3-CH-O-),3.47-3.54(m,1H,-CH-CH-CH2-),3.38(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.33(s,3H,-O-CH3),3.31(s,3H,-O-CH3),3.23-3.27(m,1H,-CH-CH-CH2-),3.12(d,J＝8.0Hz,1H,-C-CH-CH-),3.06(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.89(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.70(m,1H,-CH-CH3),2.51(d,J＝3.6Hz,1H,-CH-CH-),2.32-2.61(m,2H,-CH2-C＝N-),2.18-2.32(m,2H,-C＝CH-CH2-CH-),1.86-2.15(m,2H,-CH-CH2-),1.72-2.18(m,4H,-CH-CH2-CH-),1.72-1.99(m,2H,-CH-CH2-CH-),1.61-1.63(m,1H,CH3-CH-CH-),1.51-1.54(m,2H,-CH-CH2-CH3),1.29-1.48(m,6H,-CH3),1.02-1.28(m,12H,-CH3),0.89-0.93(m,6H,-CH3).Compound 5b: 1 H NMR (DMSO-d 6 , δ/ppm, 400MHz): 5.87 (dd, J=14.8, 12.4Hz, 1H, -C=CH-C=C), 5.74 (dd, J=16.0, 12.0Hz,1H,-CH-CH＝CC＝C-),5.62(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.33(s,1H,-OH),5.23 (dd,J＝12.0,9.2Hz,1H,-C＝CH-CH 2 -),5.10(br,1H,-OH),5.03(d,J＝4.0Hz,1H,-CH＝C-),4.73-4.85(m,1H,-CH-OC＝O-),4.70( t,J＝3.2Hz,2H,-O-CH-CH 2 -),4.58(d,J＝16.0Hz,1H,-CH-),4.46(d,J＝12.0Hz,1H,-CH-) ,4.05(s,1H,-OH),4.01-4.04(m,1H,CH 3 -CH-),3.90(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.78(s ,3H,-CH 3 ),3.74(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.61(d,J＝4.4Hz,1H,-CH-CH-O-),3.54-3.58(m,1H, CH 3 -CH-),3.54-3.55(m,1H,CH 3 -CH-O-),3.47-3.54(m,1H,-CH-CH-CH 2 -),3.38(dd,J＝14.4, 9.6Hz,1H,-CH-CH-CH-),3.33(s,3H,-O-CH 3 ),3.31(s,3H,-O-CH 3 ),3.23-3.27(m,1H,-CH -CH-CH 2 -),3.12(d,J＝8.0Hz,1H,-C-CH-CH-),3.06(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.89(dd ,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.70(m,1H,-CH-CH 3 ),2.51(d,J＝3.6Hz,1H,-CH-CH- ),2.32-2.61(m,2H,-CH 2 -C＝N-),2.18-2.32(m,2H,-C＝CH-CH 2 -CH-),1.86-2.15(m,2H,-CH -CH 2 -),1.72-2.18(m,4H,-CH-CH 2 -CH-),1.72-1.99(m,2H,-CH-CH 2 -CH-),1.61-1.63(m,1H,CH 3 -CH-CH-),1.51-1.54(m,2H,-CH -CH 2 -CH 3 ),1.29-1.48(m,6H,-CH 3 ),1.02-1.28(m,12H,-CH 3 ),0.89-0.93(m,6H,-CH 3 ).
化合物5c：1H NMR(DMSO-d6,δ/ppm,400MHz):5.88(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.74(dd,J＝16.0,12.0Hz,1H,-CH-CH＝C-C＝C-),5.60(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.34(s,1H,-OH),5.23(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH2-),5.10(br,1H,-OH),5.08(d,J＝4.0Hz,1H,-CH＝C-),4.77-4.80(m,1H,-CH-O-C＝O-),4.71(t,J＝3.2Hz,2H,-O-CH-CH2-),4.58(d,J＝16.0Hz,1H,-CH-),4.45(d,J＝12.0Hz,1H,-CH-),4.08(s,1H,-OH),3.95-4.03(m,1H,CH3-CH-),3.90(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.75(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.61(d,J＝4.4Hz,1H,-CH-CH-O-),3.51-3.60(m,2H,-O-CH2-CH3),3.54-3.57(m,1H,CH3-CH-),3.54-3.55(m,1H,CH3-CH-O-),3.47-3.54(m,1H,-CH-CH-CH2-),3.38(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.33(s,3H,-O-CH3),3.31(s,3H,-O-CH3),3.23-3.27(m,1H,-CH-CH-CH2-),3.13(d,J＝8.0Hz,1H,-C-CH-CH-),3.05(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.89(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.71(m,1H,-CH-CH3),2.51(d,J＝3.6Hz,1H,-CH-CH-),2.35-2.61(m,2H,-CH2-C＝N-),2.21-2.32(m,2H,-C＝CH-CH2-CH-),1.84-2.14(m,2H,-CH-CH2-),1.72-2.18(m,4H,-CH-CH2-CH-),1.72-1.99(m,2H,-CH-CH2-CH-),1.60-1.63(m,1H,CH3-CH-CH-),1.50-1.54(m,2H,-CH-CH2-CH3),1.30-1.48(m,6H,-CH3),1.10-1.30(m,12H,-CH3),0.81-0.96(m,6H,-CH3).Compound 5c: 1 H NMR (DMSO-d 6 , δ/ppm, 400MHz): 5.88 (dd, J = 14.8, 12.4Hz, 1H, -C = CH-C = C), 5.74 (dd, J = 16.0, 12.0Hz,1H,-CH-CH＝CC＝C-),5.60(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.34(s,1H,-OH),5.23 (dd,J＝12.0,9.2Hz,1H,-C＝CH-CH 2 -),5.10(br,1H,-OH),5.08(d,J＝4.0Hz,1H,-CH＝C-),4.77-4.80(m,1H,-CH-OC＝O-),4.71( t,J＝3.2Hz,2H,-O-CH-CH 2 -),4.58(d,J＝16.0Hz,1H,-CH-),4.45(d,J＝12.0Hz,1H,-CH-) ,4.08(s,1H,-OH),3.95-4.03(m,1H,CH 3 -CH-),3.90(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.75(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.61(d, J＝4.4Hz,1H,-CH-CH-O-),3.51-3.60(m,2H,-O-CH 2 -CH 3 ),3.54-3.57(m,1H,CH 3 -CH-),3.54 -3.55(m,1H,CH 3 -CH-O-),3.47-3.54(m,1H,-CH-CH-CH 2 -),3.38(dd,J＝14.4,9.6Hz,1H,-CH- CH-CH-),3.33(s,3H,-O-CH 3 ),3.31(s,3H,-O-CH 3 ),3.23-3.27(m,1H,-CH-CH-CH 2 -),3.13(d,J＝8.0Hz,1H,-C-CH-CH-),3.05(d,J＝14.4Hz,1H ,-C＝O-CH-CH＝C-),2.89(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.71(m,1H,-CH-CH 3 ) ,2.51(d,J＝3.6Hz,1H,-CH-CH-),2.35-2.61(m,2H,-CH 2 -C＝N-),2.21-2.32(m,2H,-C＝CH- CH 2 -CH-),1.84-2.14(m,2H,-CH-CH 2 -),1.72-2.18(m,4H,-CH-CH 2 -CH-),1.72-1.99(m,2H,-CH-CH 2 -CH-),1.60-1.63(m,1H,CH 3 - CH-CH-),1.50-1.54(m,2H,-CH-CH 2 -CH 3 ),1.30-1.48(m,6H,-CH 3 ),1.10-1.30(m,12H,-CH 3 ), 0.81-0.96(m,6H,-CH 3 ).
化合物5d：1H NMR(DMSO-d6,δ/ppm,400MHz):7.27-1.38(m,5H,Ph-H),5.88(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.76(dd,J＝16.0,12.0Hz,1H,-CH-CH＝C-C＝C-),5.63(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.34(s,1H,-OH),5.24(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH2-),5.13(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),5.01-5.09(m,2H,-O-CH2-CH3),4.80-4.87(m,1H,-CH-O-C＝O-),4.73(t,J＝3.2Hz,2H,-O-CH-CH2-),4.59(d,J＝16.0Hz,1H,-CH-),4.45(d,J＝12.0Hz,1H,-CH-),4.09(s,1H,-OH),4.01-4.04(m,1H,CH3-CH-),3.91(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.77(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.62(d,J＝4.4Hz,1H,-CH-CH-O-),3.55-3.57(m,1H,CH3-CH-),3.54-3.55(m,1H,CH3-CH-O-),3.47-3.54(m,1H,-CH-CH-CH2-),3.39(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.33(s,3H,-O-CH3),3.31(s,3H,-O-CH3),3.22-3.24(m,1H,-CH-CH-CH2-),3.17(d,J＝8.0Hz,1H,-C-CH-CH-),3.06(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.90(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.71(m,1H,-CH-CH3),2.51(d,J＝3.6Hz,1H,-CH-CH-),2.35-2.62(m,2H,-CH2-C＝N-),2.23-2.33(m,2H,-C＝CH-CH2-CH-),1.86-2.18(m,2H,-CH-CH2-),1.72-2.15(m,4H,-CH-CH2-CH-),1.72-1.99(m,2H,-CH-CH2-CH-),1.61-1.62(m,1H,CH3-CH-CH-),1.50-1.54(m,2H,-CH-CH2-CH3),1.29-1.48(m,6H,-CH3),0.98-1.26(m,12H,-CH3),0.89-0.96(m,6H,-CH3).Compound 5d: 1 H NMR (DMSO-d 6 , δ/ppm, 400MHz): 7.27-1.38 (m, 5H, Ph-H), 5.88 (dd, J＝14.8, 12.4Hz, 1H, -C＝CH- C＝C),5.76(dd,J＝16.0,12.0Hz,1H,-CH-CH＝CC＝C-),5.63(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C ),5.34(s,1H,-OH),5.24(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH 2 -),5.13(br,1H,-OH),5.04(d,J ＝4.0Hz,1H,-CH＝C-),5.01-5.09(m,2H,-O-CH 2 -CH 3 ),4.80-4.87(m,1H,-CH-OC＝O-),4.73(t,J＝3.2Hz,2H,-O-CH-CH 2 -),4.59(d,J＝16.0 Hz,1H,-CH-),4.45(d,J＝12.0Hz,1H,-CH-),4.09(s,1H,-OH),4.01-4.04(m,1H,CH 3 -CH-), 3.91(d,J＝2.8Hz,1H,-C＝C-CH-OH), 3.77(dd,J＝9.2,6.4Hz,1H,-CH-CH-), 3.62(d,J＝4.4Hz, 1H,-CH-CH-O-),3.55-3.57(m,1H,CH 3 -CH-),3.54-3.55(m,1H,CH 3 -CH-O-),3.47-3.54(m,1H,-CH-CH-CH 2 -),3.39(dd,J＝14.4,9.6Hz ,1H,-CH-CH-CH-),3.33(s,3H,-O-CH 3 ),3.31(s,3H,-O-CH 3 ),3.22-3.24(m,1H,-CH-CH -CH 2 -),3.17(d,J＝8.0Hz,1H,-C-CH-CH-),3.06(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.90(dd ,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.71(m,1H,-CH-CH 3 ),2.51(d,J＝3.6Hz,1H,-CH-CH- ),2.35-2.62(m,2H,-CH 2 -C＝N-),2.23-2.33(m,2H,-C＝CH-CH 2 -CH-),1.86-2.18(m,2H,-CH -CH 2 -),1.72-2.15(m,4H,-CH-CH 2 -CH-),1.72-1.99(m,2H,-CH-CH 2 -CH-),1.61-1.62(m,1H,CH 3 -CH-CH-),1.50-1.54(m,2H,-CH -CH 2 -CH 3 ),1.29-1.48(m,6H,-CH 3 ),0.98-1.26(m,12H,-CH 3 ),0.89-0.96(m,6H,-CH 3 ).
化合物5e：1H NMR(DMSO-d6,δ/ppm,400MHz):5.88(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.76(dd,J＝16.0,12.0Hz,1H,-CH-CH＝C-C＝C-),5.61(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.37(s,1H,-OH),5.24(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH2-),5.22-5.24(t,J＝3.2Hz,1H,-CH-CH2-),5.16(d,J＝4.0Hz,1H,-CH＝C-),5.10(br,1H,-OH),4.73-4.86(m,1H,-CH-O-C＝O-),4.70(t,J＝3.2Hz,2H,-O-CH-CH2-),4.57(d,J＝16.0Hz,1H,-CH-),4.45(d,J＝12Hz,1H,-CH-),4.07(s,1H,-OH),4.00-4.06(m,1H,CH3-CH-),3.89(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.75(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.67-3.74(m,2H,-CH2-CH3-),3.62(d,J＝4.4Hz,1H,-CH-CH-O-),3.56-3.57(m,1H,CH3-CH-),3.53-3.56(m,1H,CH3-CH-O-),3.45-3.53(m,1H,-CH-CH-CH2-),3.40(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.32(s,3H,-O-CH3),3.30(s,3H,-O-CH3),3.22-3.27(m,1H,-CH-CH-CH2-),3.12(d,J＝8.0Hz,1H,-C-CH-CH-),3.07(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.89(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.68(m,1H,-CH-CH3),2.50(d,J＝3.6Hz,1H,-CH-CH-),2.36-2.63(m,2H,-CH2-C＝N-),2.26-2.34(m,2H,-C＝CH-CH2-CH-),1.84-2.09(m,2H,-CH-CH2-),1.72-2.17(m,4H,-CH-CH2-CH-),1.66-1.99(m,2H,-CH-CH2-CH-),1.63-1.82(m,2H,-CH-CH2-CH2-),1.29-1.63(m,13H),1.09-1.29(m,12H,-CH3),0.89-0.94(m,6H,-CH3).Compound 5e: 1 H NMR (DMSO-d 6 , δ/ppm, 400MHz): 5.88 (dd, J=14.8, 12.4Hz, 1H, -C=CH-C=C), 5.76 (dd, J=16.0, 12.0Hz,1H,-CH-CH＝CC＝C-),5.61(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.37(s,1H,-OH),5.24 (dd,J＝12.0,9.2Hz,1H,-C＝CH-CH 2 -),5.22-5.24(t,J＝3.2Hz,1H,-CH-CH 2 -),5.16(d,J＝4.0Hz,1H,-CH＝C-),5.10(br,1H,-OH),4.73-4.86(m,1H,-CH-OC＝O-),4.70( t,J＝3.2Hz,2H,-O-CH-CH 2 -),4.57(d,J＝16.0Hz,1H,-CH-),4.45(d,J＝12Hz,1H,-CH-), 4.07(s,1H,-OH),4.00-4.06(m,1H,CH 3 -CH-),3.89(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.75(dd, J＝9.2,6.4Hz,1H,-CH-CH-),3.67-3.74(m,2H,-CH 2 -CH 3 -),3.62(d,J＝4.4Hz,1H,-CH-CH-O-),3.56-3.57(m,1H,CH 3 -CH-),3.53-3.56(m,1H,CH 3 -CH -O-),3.45-3.53(m,1H,-CH-CH-CH 2 -),3.40(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.32(s,3H ,-O-CH 3 ),3.30(s,3H,-O-CH 3 ),3.22-3.27(m,1H,-CH-CH-CH 2 -),3.12(d,J＝8.0Hz,1H,-C-CH-CH-),3.07(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.89(dd ,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.68(m,1H,-CH-CH 3 ),2.50(d,J＝3.6Hz,1H,-CH-CH- ),2.36-2.63(m,2H,-CH 2 -C＝N-),2.26-2.34(m,2H,-C＝CH-CH 2 -CH-),1.84-2.09(m,2H,-CH -CH 2 -),1.72-2.17(m,4H,-CH-CH 2 -CH-),1.66-1.99(m,2H,-CH-CH 2 -CH-),1.63-1.82(m,2H,-CH-CH 2 -CH 2 -),1.29-1.63(m,13H) ,1.09-1.29(m,12H,-CH 3 ),0.89-0.94(m,6H,-CH 3 ).
化合物5f：1H NMR(DMSO-d6,δ/ppm,400MHz):7.07-7.49(m,15H,Ph-H),5.89(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.79(dd,J＝16.0,12.0Hz,1H,-CH-CH＝C-C＝C-),5.64(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.33(s,1H,-OH),5.27(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH2-),5.10(br,1H,-OH),5.05(d,J＝4.0Hz,1H,-CH＝C-),4.75-4.84(m,1H,-CH-O-C＝O-),4.68(t,J＝3.2Hz,2H,-O-CH-CH2-),4.59(d,J＝16.0Hz,1H,-CH-),4.49(d,J＝12Hz,1H,-CH-),4.12(s,1H,-OH),4.01-4.10(m,1H,CH3-CH-),3.93(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.79(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.67(d,J＝4.4Hz,1H,-CH-CH-O-),3.59-3.61(m,1H,CH3-CH-),3.57-3.59(m,1H,CH3-CH-O-),3.45-3.48(m,1H,-CH-CH-CH2-),3.36(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.33(s,3H,-O-CH3),3.31(s,3H,-O-CH3),3.19-3.22(m,1H,-CH-CH-CH2-),3.16(d,J＝8.0Hz,1H,-C-CH-CH-),3.10(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.93(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.64-2.71(m,1H,-CH-CH3),2.51(d,J＝3.6Hz,1H,-CH-CH-),2.43-2.57(m,2H,-CH2-C＝N-),2.33-2.42(m,2H,-C＝CH-CH2-CH-),1.85-2.12(m,2H,-CH-CH2-),1.74-2.15(m,4H,-CH-CH2-CH-),1.64-1.99(m,2H,-CH-CH2-CH-),1.61-1.67(m,1H,CH3-CH-CH-),1.50-1.59(m,2H,-CH-CH2-CH3),1.27-1.48(m,6H,-CH3),1.08-1.27(m,12H,-CH3),0.69-0.90(m,6H,-CH3).Compound 5f: 1 H NMR (DMSO-d 6 , δ/ppm, 400MHz): 7.07-7.49 (m, 15H, Ph-H), 5.89 (dd, J＝14.8, 12.4Hz, 1H, -C＝CH- C＝C),5.79(dd,J＝16.0,12.0Hz,1H,-CH-CH＝CC＝C-),5.64(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C ),5.33(s,1H,-OH),5.27(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH 2 -),5.10(br,1H,-OH),5.05(d,J＝4.0Hz,1H,-CH＝C-),4.75-4.84(m,1H,-CH-OC＝O-),4.68( t,J＝3.2Hz,2H,-O-CH-CH 2 -),4.59(d,J＝16.0Hz,1H,-CH-),4.49(d,J＝12Hz,1H,-CH-), 4.12(s,1H,-OH),4.01-4.10(m,1H,CH 3 -CH-),3.93(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.79(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.67(d, J＝4.4Hz,1H,-CH-CH-O-),3.59-3.61(m,1H,CH 3 -CH-),3.57-3.59(m,1H,CH 3 -CH-O-),3.45- 3.48(m,1H,-CH-CH-CH 2 -),3.36(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.33(s,3H,-O-CH 3 ) ,3.31(s,3H,-O-CH 3 ),3.19-3.22(m,1H,-CH-CH-CH 2 -),3.16(d,J＝8.0Hz,1H,-C-CH-CH-),3.10(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.93(dd ,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.64-2.71(m,1H,-CH-CH 3 ),2.51(d,J＝3.6Hz,1H,-CH-CH- ),2.43-2.57(m,2H,-CH 2 -C＝N-),2.33-2.42(m,2H,-C＝CH-CH 2 -CH-),1.85-2.12(m,2H,-CH -CH 2 -),1.74-2.15(m,4H,-CH-CH 2 -CH-),1.64-1.99(m,2H,-CH-CH 2 -CH-),1.61-1.67(m,1H,CH 3 -CH-CH-),1.50-1.59(m,2H,-CH -CH 2 -CH 3 ),1.27-1.48(m,6H,-CH 3 ),1.08-1.27(m,12H,-CH 3 ),0.69-0.90(m,6H,-CH 3 ).
化合物5g：1H NMR(DMSO-d6,δ/ppm,400MHz):7.20(d,J＝8.0Hz,2H,Ph-H),7.12(d,J＝8.0Hz,2H,Ph-H),5.88(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.76(dd,J＝16.0,12.0Hz,1H,-CH-CH＝C-C＝C-),5.62(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.32(s,1H,-OH),5.25(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH2-),5.13(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),4.96-5.02(m,2H,-O-CH2-CH3),4.81-4.87(m,1H,-CH-O-C＝O-),4.73(t,J＝3.2Hz,2H,-O-CH-CH2-),4.58(d,J＝16.0Hz,1H,-CH-),4.47(d,J＝12.0Hz,1H,-CH-),4.10(s,1H,-OH),4.01-4.06(m,1H,CH3-CH-),3.92(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.78(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.63(d,J＝4.4Hz,1H,-CH-CH-O-),3.56-3.58(m,1H,CH3-CH-),3.54-3.55(m,1H,CH3-CH-O-),3.47-3.54(m,1H,-CH-CH-CH2-),3.39(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.34(s,3H,-O-CH3),3.31(s,3H,-O-CH3),3.26-3.28(m,1H,-CH-CH-CH2-),3.16(d,J＝8.0Hz,1H,-C-CH-CH-),3.07(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.91(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.71(m,1H,-CH-CH3),2.51(d,J＝3.6Hz,1H,-CH-CH-),2.34-2.62(m,2H,-CH2-C＝N-),2.29(s,3H,-O-CH3),2.20-2.30(m,2H,-C＝CH-CH2-CH-),1.86-2.20(m,2H,-CH-CH2-),1.74-2.16(m,4H,-CH-CH2-CH-),1.73-1.99(m,2H,-CH-CH2-CH-),1.60-1.67(m,1H,CH3-CH-CH-),1.50-1.53(m,2H,-CH-CH2-CH3),1.33-1.49(m,6H,-CH3),1.03-1.30(m,12H,-CH3),0.85-0.94(m,6H,-CH3).Compound 5g: 1 H NMR (DMSO-d 6 , δ/ppm, 400MHz): 7.20 (d, J = 8.0 Hz, 2H, Ph-H), 7.12 (d, J = 8.0 Hz, 2H, Ph-H) ,5.88(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.76(dd,J＝16.0,12.0Hz,1H,-CH-CH＝CC＝C-),5.62( dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.32(s,1H,-OH),5.25(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH 2 -),5.13(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),4.96-5.02(m,2H,-O-CH 2 -CH 3 ),4.81 -4.87(m,1H,-CH-OC＝O-),4.73(t,J＝3.2Hz,2H,-O-CH-CH 2 -),4.58(d,J＝16.0Hz,1H,-CH -),4.47(d,J＝12.0Hz,1H,-CH-),4.10(s,1H,-OH),4.01-4.06(m,1H,CH 3 -CH-),3.92(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.78(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.63(d, J＝4.4Hz,1H,-CH-CH-O-),3.56-3.58(m,1H,CH 3 -CH-),3.54-3.55(m,1H,CH 3 -CH-O-),3.47- 3.54(m,1H,-CH-CH-CH 2 -),3.39(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.34(s,3H,-O-CH 3 ) ,3.31(s,3H,-O-CH 3 ),3.26-3.28(m,1H,-CH-CH-CH 2 -),3.16(d,J＝8.0Hz,1H,-C-CH-CH-),3.07(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.91(dd ,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.71(m,1H,-CH-CH 3 ),2.51(d,J＝3.6Hz,1H,-CH-CH- ),2.34-2.62(m,2H,-CH 2 -C＝N-),2.29(s,3H,-O-CH 3 ),2.20-2.30(m,2H,-C＝CH-CH 2 -CH -),1.86-2.20(m,2H,-CH-CH 2 -),1.74-2.16(m,4H,-CH-CH 2 -CH-),1.73-1.99(m,2H,-CH-CH 2 -CH-),1.60-1.67(m,1H,CH 3 -CH-CH-),1.50-1.53(m,2H,- CH-CH 2 -CH 3 ),1.33-1.49(m,6H,-CH 3 ),1.03-1.30(m,12H,-CH 3 ),0.85-0.94(m,6H,-CH 3 ).
化合物5h：1H NMR(DMSO-d6,δ/ppm,400MHz):7.37(d,J＝8.0Hz,2H,Ph-H),7.16(d,J＝8.0Hz,2H,Ph-H),5.88(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.76(dd,J＝16.0,12.0Hz,1H,-CH-CH＝C-C＝C-),5.62(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.35(s,1H,-OH),5.25(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH2-),5.12(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),4.99-5.10(m,2H,-O-CH2-CH3),4.79-4.85(m,1H,-CH-O-C＝O-),4.73(t,J＝3.2Hz,2H,-O-CH-CH2-),4.58(d,J＝16.0Hz,1H,-CH-),4.45(d,J＝12.0Hz,1H,-CH-),4.08(s,1H,-OH),4.01-4.06(m,1H,CH3-CH-),3.91(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.77(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.62(d,J＝4.4Hz,1H,-CH-CH-O-),3.55-3.59(m,1H,CH3-CH-),3.54-3.55(m,1H,CH3-CH-O-),3.47-3.54(m,1H,-CH-CH-CH2-),3.38(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.33(s,3H,-O-CH3),3.31(s,3H,-O-CH3),3.22-3.28(m,1H,-CH-CH-CH2-),3.13(d,J＝8.0Hz,1H,-C-CH-CH-),3.05(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.90(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.71(m,1H,-CH-CH3),2.51(d,J＝3.6Hz,1H,-CH-CH-),2.34-2.62(m,2H,-CH2-C＝N-),2.20-2.32(m,2H,-C＝CH-CH2-CH-),1.86-2.15(m,2H,-CH-CH2-),1.72-2.03(m,4H,-CH-CH2-CH-),1.72-1.99(m,2H,-CH-CH2-CH-),1.60-1.63(m,1H,CH3-CH-CH-),1.50-1.54(m,2H,-CH-CH2-CH3),1.28-1.47(m,6H,-CH3),1.10-1.23(m,12H,-CH3),0.87-0.96(m,6H,-CH3).Compound 5h: 1 H NMR (DMSO-d 6 , δ/ppm, 400MHz): 7.37 (d, J = 8.0 Hz, 2H, Ph-H), 7.16 (d, J = 8.0 Hz, 2H, Ph-H) ,5.88(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.76(dd,J＝16.0,12.0Hz,1H,-CH-CH＝CC＝C-),5.62( dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.35(s,1H,-OH),5.25(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH 2 -),5.12(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),4.99-5.10(m,2H,-O-CH 2 -CH 3 ),4.79 -4.85(m,1H,-CH-OC＝O-),4.73(t,J＝3.2Hz,2H,-O-CH-CH 2 -),4.58(d,J＝16.0Hz,1H,-CH -),4.45(d,J＝12.0Hz,1H,-CH-),4.08(s,1H,-OH),4.01-4.06(m,1H,CH 3 -CH-),3.91(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.77(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.62(d, J＝4.4Hz,1H,-CH-CH-O-),3.55-3.59(m,1H,CH 3 -CH-),3.54-3.55(m,1H,CH 3 -CH-O-),3.47- 3.54(m,1H,-CH-CH-CH 2 -),3.38(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.33(s,3H,-O-CH 3 ) ,3.31(s,3H,-O-CH 3 ),3.22-3.28(m,1H,-CH-CH-CH 2 -),3.13(d,J＝8.0Hz,1H,-C-CH-CH-),3.05(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.90(dd ,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.71(m,1H,-CH-CH 3 ),2.51(d,J＝3.6Hz,1H,-CH-CH- ),2.34-2.62(m,2H,-CH 2 -C＝N-),2.20-2.32(m,2H,-C＝CH-CH 2 -CH-),1.86-2.15(m,2H,-CH -CH 2 -),1.72-2.03(m,4H,-CH-CH 2 -CH-),1.72-1.99(m,2H,-CH-CH 2 -CH-),1.60-1.63(m,1H,CH 3 -CH-CH-),1.50-1.54(m,2H,-CH -CH 2 -CH 3 ),1.28-1.47(m,6H,-CH 3 ),1.10-1.23(m,12H,-CH 3 ),0.87-0.96(m,6H,-CH 3 ).
化合物5i：1H NMR(DMSO-d6,δ/ppm,400MHz):7.47(d,J＝8.0Hz,1H,Ph-H),7.39(d,J＝8.0Hz,2H,Ph-H),5.88(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.73(dd,J＝16.0,12.0Hz,1H,-CH-CH＝C-C＝C-),5.60(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.33(s,1H,-OH),5.23(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH2-),5.20(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),5.04-5.09(m,2H,-O-CH2-CH3),4.76-4.81(m,1H,-CH-O-C＝O-),4.71(t,J＝3.2Hz,2H,-O-CH-CH2-),4.58(d,J＝16.0Hz,1H,-CH-),4.45(d,J＝12.0Hz,1H,-CH-),4.07(s,1H,-OH),4.00-4.06(m,1H,CH3-CH-),3.90(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.75(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.60(d,J＝4.4Hz,1H,-CH-CH-O-),3.54-3.58(m,1H,CH3-CH-),3.54-3.55(m,1H,CH3-CH-O-),3.47-3.54(m,1H,-CH-CH-CH2-),3.34(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.32(s,3H,-O-CH3),3.30(s,3H,-O-CH3),3.24-3.28(m,1H,-CH-CH-CH2-),3.12(d,J＝8.0Hz,1H,-C-CH-CH-),3.05(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.89(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.62-2.71(m,1H,-CH-CH3),2.51(d,J＝3.6Hz,1H,-CH-CH-),2.33-2.58(m,2H,-CH2-C＝N-),2.21-2.30(m,2H,-C＝CH-CH2-CH-),1.92-2.16(m,2H,-CH-CH2-),1.71-1.99(m,4H,-CH-CH2-CH-),1.71-1.99(m,2H,-CH-CH2-CH-),1.61-1.66(m,1H,CH3-CH-CH-),1.50-1.53(m,2H,-CH-CH2-CH3),1.30-1.47(m,6H,-CH3),1.02-1.30(m,12H,-CH3),0.86-0.93(m,6H,-CH3).Compound 5i: 1 H NMR (DMSO-d 6 , δ/ppm, 400MHz): 7.47 (d, J = 8.0 Hz, 1H, Ph-H), 7.39 (d, J = 8.0 Hz, 2H, Ph-H) ,5.88(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.73(dd,J＝16.0,12.0Hz,1H,-CH-CH＝CC＝C-),5.60( dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.33(s,1H,-OH),5.23(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH 2 -),5.20(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),5.04-5.09(m,2H,-O-CH 2 -CH 3 ),4.76 -4.81(m,1H,-CH-OC＝O-),4.71(t,J＝3.2Hz,2H,-O-CH-CH 2 -),4.58(d,J＝16.0Hz,1H,-CH -),4.45(d,J＝12.0Hz,1H,-CH-),4.07(s,1H,-OH),4.00-4.06(m,1H,CH 3 -CH-),3.90(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.75(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.60(d, J＝4.4Hz,1H,-CH-CH-O-),3.54-3.58(m,1H,CH 3 -CH-),3.54-3.55(m,1H,CH 3 -CH-O-),3.47- 3.54(m,1H,-CH-CH-CH 2 -),3.34(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.32(s,3H,-O-CH 3 ) ,3.30(s,3H,-O-CH 3 ),3.24-3.28(m,1H,-CH-CH-CH 2 -),3.12(d,J＝8.0Hz,1H,-C-CH-CH-),3.05(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.89(dd ,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.62-2.71(m,1H,-CH-CH 3 ),2.51(d,J＝3.6Hz,1H,-CH-CH- ),2.33-2.58(m,2H,-CH 2 -C＝N-),2.21-2.30(m,2H,-C＝CH-CH 2 -CH-),1.92-2.16(m,2H,-CH -CH 2 -),1.71-1.99(m,4H,-CH-CH 2 -CH-),1.71-1.99(m,2H,-CH-CH 2 -CH-),1.61-1.66(m,1H,CH 3 -CH-CH-),1.50-1.53(m,2H,-CH -CH 2 -CH 3 ),1.30-1.47(m,6H,-CH 3 ),1.02-1.30(m,12H,-CH 3 ),0.86-0.93(m,6H,-CH 3 ).
化合物5j：1H NMR(DMSO-d6,δ/ppm,400M Hz):7.34(d,J＝12.0Hz,2H,Ph-H),7.26(d,J＝8.0Hz,2H,Ph-H),5.88(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.74(dd,J＝16.0,12.0Hz,1H,-CH-CH＝C-C＝C-),5.61(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.32(s,1H,-OH),5.25(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH2-),5.12(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),4.96-5.04(m,2H,-O-CH2-CH3),4.71-4.76(m,1H,-CH-O-C＝O-),4.72(t,J＝3.2Hz,2H,-O-CH-CH2-),4.59(d,J＝16.0Hz,1H,-CH-),4.46(d,J＝12.0Hz,1H,-CH-),4.10(s,1H,-OH),4.01-4.08(m,1H,CH3-CH-),3.91(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.77(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.63(d,J＝4.4Hz,1H,-CH-CH-O-),3.56-3.58(m,1H,CH3-CH-),3.54-3.55(m,1H,CH3-CH-O-),3.47-3.54(m,1H,-CH-CH-CH2-),3.39(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.33(s,3H,-O-CH3),3.31(s,3H,-O-CH3),3.20-3.25(m,1H,-CH-CH-CH2-),3.14(d,J＝8.0Hz,1H,-C-CH-CH-),3.07(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.91(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.71(m,1H,-CH-CH3),2.51(d,J＝3.6Hz,1H,-CH-CH-),2.35-2.62(m,2H,-CH2-C＝N-),2.20-2.33(m,2H,-C＝CH-CH2-CH-),1.96-2.15(m,2H,-CH-CH2-),1.73-2.01(m,4H,-CH-CH2-CH-),1.73-1.99(m,2H,-CH-CH2-CH-),1.61-1.67(m,1H,CH3-CH-CH-),1.50-1.54(m,2H,-CH-CH2-CH3),1.38-1.48(m,6H,-CH3),1.10-1.26(m,21H,-CH3),0.81-0.96(m,6H,-CH3).Compound 5j: 1 H NMR (DMSO-d 6 , δ/ppm, 400M Hz): 7.34 (d, J = 12.0 Hz, 2H, Ph-H), 7.26 (d, J = 8.0 Hz, 2H, Ph-H ),5.88(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.74(dd,J＝16.0,12.0Hz,1H,-CH-CH＝CC＝C-),5.61 (dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.32(s,1H,-OH),5.25(dd,J＝12.0,9.2Hz,1H,-C＝CH- CH 2 -),5.12(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),4.96-5.04(m,2H,-O-CH 2 -CH 3 ),4.71 -4.76(m,1H,-CH-OC＝O-),4.72(t,J＝3.2Hz,2H,-O-CH-CH 2 -),4.59(d,J＝16.0Hz,1H,-CH -),4.46(d,J＝12.0Hz,1H,-CH-),4.10(s,1H,-OH),4.01-4.08(m,1H,CH 3 -CH-),3.91(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.77(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.63(d, J＝4.4Hz,1H,-CH-CH-O-),3.56-3.58(m,1H,CH 3 -CH-),3.54-3.55(m,1H,CH 3 -CH-O-),3.47- 3.54(m,1H,-CH-CH-CH 2 -),3.39(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.33(s,3H,-O-CH 3 ) ,3.31(s,3H,-O-CH 3 ),3.20-3.25(m,1H,-CH-CH-CH 2 -),3.14(d,J＝8.0Hz,1H,-C-CH-CH-),3.07(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.91(dd ,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.71(m,1H,-CH-CH 3 ),2.51(d,J＝3.6Hz,1H,-CH-CH- ),2.35-2.62(m,2H,-CH 2 -C＝N-),2.20-2.33(m,2H,-C＝CH-CH 2 -CH-),1.96-2.15(m,2H,-CH -CH 2 -),1.73-2.01(m,4H,-CH-CH 2 -CH-),1.73-1.99(m,2H,-CH-CH 2 -CH-),1.61-1.67(m,1H,CH 3 -CH-CH-),1.50-1.54(m,2H,-CH -CH 2 -CH 3 ),1.38-1.48(m,6H,-CH 3 ),1.10-1.26(m,21H,-CH 3 ),0.81-0.96(m,6H,-CH 3 ).
化合物5k：1H NMR(DMSO-d6,δ/ppm,400MHz):7.27(d,J＝12.0Hz,2H,Ph-H),6.88(d,J＝12.0Hz,2H,Ph-H),5.89(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.78(dd,J＝16.0,12.0Hz,1H,-CH-CH＝C-C＝C-),5.63(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.36(s,1H,-OH),5.25(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH2-),5.13(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),4.93-5.06(m,2H,-O-CH2-CH3),4.80-4.84(m,1H,-CH-O-C＝O-),4.73(t,J＝3.2Hz,2H,-O-CH-CH2-),4.58(d,J＝16.0Hz,1H,-CH-),4.47(d,J＝12.0Hz,1H,-CH-),4.10(s,1H,-OH),4.02-4.07(m,1H,CH3-CH-),3.92(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.78(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.74(s,3H,-O-CH3),3.64(d,J＝4.4Hz,1H,-CH-CH-O-),3.56-3.58(m,1H,CH3-CH-),3.54-3.55(m,1H,CH3-CH-O-),3.47-3.54(m,1H,-CH-CH-CH2-),3.40(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.34(s,3H,-O-CH3),3.32(s,3H,-O-CH3),3.26-3.28(m,1H,-CH-CH-CH2-),3.14(d,J＝8.0Hz,1H,-C-CH-CH-),3.07(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.92(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.64-2.71(m,1H,-CH-CH3),2.52(d,J＝3.6Hz,1H,-CH-CH-),2.35-2.62(m,2H,-CH2-C＝N-),2.21-2.32(m,2H,-C＝CH-CH2-CH-),1.85-2.21(m,2H,-CH-CH2-),1.74-2.16(m,4H,-CH-CH2-CH-),1.74-2.00(m,2H,-CH-CH2-CH-),1.61-1.68(m,1H,CH3-CH-CH-),1.50-1.54(m,2H,-CH-CH2-CH3),1.29-1.49(m,6H,-CH3),1.04-1.27(m,12H,-CH3),0.90-0.96(m,6H,-CH3).Compound 5k: 1 H NMR (DMSO-d 6 , δ/ppm, 400MHz): 7.27 (d, J = 12.0 Hz, 2H, Ph-H), 6.88 (d, J = 12.0 Hz, 2H, Ph-H) ,5.89(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.78(dd,J＝16.0,12.0Hz,1H,-CH-CH＝CC＝C-),5.63( dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.36(s,1H,-OH),5.25(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH 2 -),5.13(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),4.93-5.06(m,2H,-O-CH 2 -CH 3 ),4.80 -4.84(m,1H,-CH-OC＝O-),4.73(t,J＝3.2Hz,2H,-O-CH-CH 2 -),4.58(d,J＝16.0Hz,1H,-CH -),4.47(d,J＝12.0Hz,1H,-CH-),4.10(s,1H,-OH),4.02-4.07(m,1H,CH 3 -CH-),3.92(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.78(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.74(s, 3H,-O-CH 3 ),3.64(d,J＝4.4Hz,1H,-CH-CH-O-),3.56-3.58(m,1H,CH 3 -CH-),3.54-3.55(m, 1H,CH 3 -CH-O-),3.47-3.54(m,1H,-CH-CH-CH 2 -),3.40(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-) ,3.34(s,3H,-O-CH 3 ),3.32(s,3H,-O-CH 3 ),3.26-3.28(m,1H,-CH-CH-CH 2 -),3.14(d,J＝8.0Hz,1H,-C-CH-CH-),3.07(d,J＝14.4Hz,1H ,-C＝O-CH-CH＝C-),2.92(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.64-2.71(m,1H,-CH-CH 3 ) ,2.52(d,J＝3.6Hz,1H,-CH-CH-),2.35-2.62(m,2H,-CH 2 -C＝N-),2.21-2.32(m,2H,-C＝CH- CH 2 -CH-),1.85-2.21(m,2H,-CH-CH 2 -),1.74-2.16(m,4H,-CH-CH 2 -CH-),1.74-2.00(m,2H,-CH-CH 2 -CH-),1.61-1.68(m,1H,CH 3 - CH-CH-),1.50-1.54(m,2H,-CH-CH 2 -CH 3 ),1.29-1.49(m,6H,-CH 3 ),1.04-1.27(m,12H,-CH 3 ), 0.90-0.96(m,6H,-CH 3 ).
化合物5l：1H NMR(DMSO-d6,δ/ppm,400MHz):7.78(d,J＝12.0Hz,2H,Ph-H),7.49(d,J＝8.0Hz,2H,Ph-H),5.88(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.76(dd,J＝16.0,12.0Hz,1H,-CH-CH＝C-C＝C-),5.61(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.35(s,1H,-OH),5.24(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH2-),5.19(br,1H,-OH),5.14(d,J＝4.0Hz,1H,-CH＝C-),5.11-5.15(m,2H,-O-CH2-CH3),4.80-4.85(m,1H,-CH-O-C＝O-),4.73(t,J＝3.2Hz,2H,-O-CH-CH2-),4.58(d,J＝16.0Hz,1H,-CH-),4.46(d,J＝12.0Hz,1H,-CH-),4.09(s,1H,-OH),4.00-4.05(m,1H,CH3-CH-),3.91(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.77(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.63(d,J＝4.4Hz,1H,-CH-CH-O-),3.55-3.57(m,1H,CH3-CH-),3.54-3.55(m,1H,CH3-CH-O-),3.47-3.54(m,1H,-CH-CH-CH2-),3.37(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.32(s,3H,-O-CH3),3.31(s,3H,-O-CH3),3.21-3.28(m,1H,-CH-CH-CH2-),3.12(d,J＝8.0Hz,1H,-C-CH-CH-),3.06(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.90(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.71(m,1H,-CH-CH3),2.51(d,J＝3.6Hz,1H,-CH-CH-),2.37-2.62(m,2H,-CH2-C＝N-),2.23-2.35(m,2H,-C＝CH-CH2-CH-),1.86-2.21(m,2H,-CH-CH2-),1.72-2.14(m,4H,-CH-CH2-CH-),1.72-1.98(m,2H,-CH-CH2-CH-),1.57-1.60(m,1H,CH3-CH-CH-),1.50-1.54(m,2H,-CH-CH2-CH3),1.30-1.43(m,6H,-CH3),1.13-1.19(m,12H,-CH3),0.87-0.93(m,6H,-CH3).Compound 5l: 1 H NMR (DMSO-d 6 , δ/ppm, 400MHz): 7.78 (d, J = 12.0 Hz, 2H, Ph-H), 7.49 (d, J = 8.0 Hz, 2H, Ph-H) ,5.88(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.76(dd,J＝16.0,12.0Hz,1H,-CH-CH＝CC＝C-),5.61( dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.35(s,1H,-OH),5.24(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH 2 -),5.19(br,1H,-OH),5.14(d,J＝4.0Hz,1H,-CH＝C-),5.11-5.15(m,2H,-O-CH 2 -CH 3 ),4.80 -4.85(m,1H,-CH-OC＝O-),4.73(t,J＝3.2Hz,2H,-O-CH-CH 2 -),4.58(d,J＝16.0Hz,1H,-CH -),4.46(d,J＝12.0Hz,1H,-CH-),4.09(s,1H,-OH),4.00-4.05(m,1H,CH 3 -CH-),3.91(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.77(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.63(d, J＝4.4Hz,1H,-CH-CH-O-),3.55-3.57(m,1H,CH 3 -CH-),3.54-3.55(m,1H,CH 3 -CH-O-),3.47- 3.54(m,1H,-CH-CH-CH 2 -),3.37(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.32(s,3H,-O-CH 3 ) ,3.31(s,3H,-O-CH 3 ),3.21-3.28(m,1H,-CH-CH-CH 2 -),3.12(d,J＝8.0Hz,1H,-C-CH-CH-),3.06(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.90(dd ,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.71(m,1H,-CH-CH 3 ),2.51(d,J＝3.6Hz,1H,-CH-CH- ),2.37-2.62(m,2H,-CH 2 -C＝N-),2.23-2.35(m,2H,-C＝CH-CH 2 -CH-),1.86-2.21(m,2H,-CH -CH 2 -),1.72-2.14(m,4H,-CH-CH 2 -CH-),1.72-1.98(m,2H,-CH-CH 2 -CH-),1.57-1.60(m,1H,CH 3 -CH-CH-),1.50-1.54(m,2H,-CH -CH 2 -CH 3 ),1.30-1.43(m,6H,-CH 3 ),1.13-1.19(m,12H,-CH 3 ),0.87-0.93(m,6H,-CH 3 ).
化合物5m：1H NMR(DMSO-d6,δ/ppm,400MHz):7.51(d,J＝20.0Hz,2H,Ph-H),7.27(d,J＝8.0Hz,2H,Ph-H),5.88(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.79(dd,J＝16.0,12.0Hz,1H,-CH-CH＝C-C＝C-),5.63(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.34(s,1H,-OH),5.25(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH2-),5.13(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),4.98-5.05(m,2H,-O-CH2-CH3),4.81-4.87(m,1H,-CH-O-C＝O-),4.73(t,J＝3.2Hz,2H,-O-CH-CH2-),4.58(d,J＝16.0Hz,1H,-CH-),4.56(d,J＝12.0Hz,1H,-CH-),4.11(s,1H,-OH),3.91-4.06(m,1H,CH3-CH-),3.91(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.77(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.65(d,J＝4.4Hz,1H,-CH-CH-O-),3.58-3.60(m,1H,CH3-CH-),3.54-3.55(m,1H,CH3-CH-O-),3.47-3.54(m,1H,-CH-CH-CH2-),3.37(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.33(s,3H,-O-CH3),3.31(s,3H,-O-CH3),3.19-3.22(m,1H,-CH-CH-CH2-),3.13(d,J＝8.0Hz,1H,-C-CH-CH-),3.07(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.91(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.71(m,1H,-CH-CH3),2.51(d,J＝3.6Hz,1H,-CH-CH-),2.33-2.62(m,2H,-CH2-C＝N-),2.21-2.33(m,2H,-C＝CH-CH2-CH-),1.85-2.21(m,2H,-CH-CH2-),1.74-2.21(m,4H,-CH-CH2-CH-),1.74-1.99(m,2H,-CH-CH2-CH-),1.59-1.65(m,1H,CH3-CH-CH-),1.50-1.54(m,2H,-CH-CH2-CH3),1.39-1.47(m,6H,-CH3),1.10-1.20(m,12H,-CH3),0.90-0.91(m,6H,-CH3).Compound 5m: 1 H NMR (DMSO-d 6 , δ/ppm, 400MHz): 7.51 (d, J = 20.0 Hz, 2H, Ph-H), 7.27 (d, J = 8.0 Hz, 2H, Ph-H) ,5.88(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.79(dd,J＝16.0,12.0Hz,1H,-CH-CH＝CC＝C-),5.63( dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.34(s,1H,-OH),5.25(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH 2 -),5.13(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),4.98-5.05(m,2H,-O-CH 2 -CH 3 ),4.81 -4.87(m,1H,-CH-OC＝O-),4.73(t,J＝3.2Hz,2H,-O-CH-CH 2 -),4.58(d,J＝16.0Hz,1H,-CH -),4.56(d,J＝12.0Hz,1H,-CH-),4.11(s,1H,-OH),3.91-4.06(m,1H,CH 3 -CH-),3.91(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.77(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.65(d, J＝4.4Hz,1H,-CH-CH-O-),3.58-3.60(m,1H,CH 3 -CH-),3.54-3.55(m,1H,CH 3 -CH-O-),3.47- 3.54(m,1H,-CH-CH-CH 2 -),3.37(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.33(s,3H,-O-CH 3 ) ,3.31(s,3H,-O-CH 3 ),3.19-3.22(m,1H,-CH-CH-CH 2 -),3.13(d,J＝8.0Hz,1H,-C-CH-CH-),3.07(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.91(dd ,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.71(m,1H,-CH-CH 3 ),2.51(d,J＝3.6Hz,1H,-CH-CH- ),2.33-2.62(m,2H,-CH 2 -C＝N-),2.21-2.33(m,2H,-C＝CH-CH 2 -CH-),1.85-2.21(m,2H,-CH -CH 2 -),1.74-2.21(m,4H,-CH-CH 2 -CH-),1.74-1.99(m,2H,-CH-CH 2 -CH-),1.59-1.65(m,1H,CH 3 -CH-CH-),1.50-1.54(m,2H,-CH -CH 2 -CH 3 ),1.39-1.47(m,6H,-CH 3 ),1.10-1.20(m,12H,-CH 3 ),0.90-0.91(m,6H,-CH 3 ).
化合物5n：1H NMR(DMSO-d6,δ/ppm,400MHz):7.42(m,H,Ph-H),7.32(m,1H,Ph-H),7.21(m,1H,Ph-H),5.87(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.75(dd,J＝16.0,12.0Hz,1H,-CH-CH＝C-C＝C-),5.61(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.35(s,1H,-OH),5.24(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH2-),5.11(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),5.04-5.06(m,2H,-O-CH2-CH3),4.77-4.89(m,1H,-CH-O-C＝O-),4.68(t,J＝3.2Hz,2H,-O-CH-CH2-),4.58(d,J＝16.0Hz,1H,-CH-),4.45(d,J＝12.0Hz,1H,-CH-),4.08(s,1H,-OH),4.00-4.06(m,1H,CH3-CH-),3.90(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.76(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.62(d,J＝4.4Hz,1H,-CH-CH-O-),3.55-3.58(m,1H,CH3-CH-),3.54-3.55(m,1H,CH3-CH-O-),3.47-3.54(m,1H,-CH-CH-CH2-),3.37(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.32(s,3H,-O-CH3),3.30(s,3H,-O-CH3),3.24-3.28(m,1H,-CH-CH-CH2-),3.12(d,J＝8.0Hz,1H,-C-CH-CH-),3.06(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.90(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.71(m,1H,-CH-CH3),2.51(d,J＝3.6Hz,1H,-CH-CH-),2.30-2.62(m,2H,-CH2-C＝N-),2.21-2.29(m,2H,-C＝CH-CH2-CH-),1.96-2.15(m,2H,-CH-CH2-),1.72-2.15(m,4H,-CH-CH2-CH-),1.72-1.99(m,2H,-CH-CH2-CH-),1.56-1.59(m,1H,CH3-CH-CH-),1.54-1.57(m,2H,-CH-CH2-CH3),1.30-1.40(m,6H,-CH3),1.02-1.19(m,12H,-CH3),0.81-0.92(m,6H,-CH3).Compound 5n: 1 H NMR (DMSO-d 6 , δ/ppm, 400MHz): 7.42 (m, H, Ph-H), 7.32 (m, 1H, Ph-H), 7.21 (m, 1H, Ph-H ),5.87(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.75(dd,J＝16.0,12.0Hz,1H,-CH-CH＝CC＝C-),5.61 (dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.35(s,1H,-OH),5.24(dd,J＝12.0,9.2Hz,1H,-C＝CH- CH 2 -),5.11(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),5.04-5.06(m,2H,-O-CH 2 -CH 3 ),4.77 -4.89(m,1H,-CH-OC＝O-),4.68(t,J＝3.2Hz,2H,-O-CH-CH 2 -),4.58(d,J＝16.0Hz,1H,-CH -),4.45(d,J＝12.0Hz,1H,-CH-),4.08(s,1H,-OH),4.00-4.06(m,1H,CH 3 -CH-),3.90(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.76(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.62(d, J＝4.4Hz,1H,-CH-CH-O-),3.55-3.58(m,1H,CH 3 -CH-),3.54-3.55(m,1H,CH 3 -CH-O-),3.47- 3.54(m,1H,-CH-CH-CH 2 -),3.37(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.32(s,3H,-O-CH 3 ) ,3.30(s,3H,-O-CH 3 ),3.24-3.28(m,1H,-CH-CH-CH 2 -),3.12(d,J＝8.0Hz,1H,-C-CH-CH-),3.06(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.90(dd ,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.71(m,1H,-CH-CH 3 ),2.51(d,J＝3.6Hz,1H,-CH-CH- ),2.30-2.62(m,2H,-CH 2 -C＝N-),2.21-2.29(m,2H,-C＝CH-CH 2 -CH-),1.96-2.15(m,2H,-CH -CH 2 -),1.72-2.15(m,4H,-CH-CH 2 -CH-),1.72-1.99(m,2H,-CH-CH 2 -CH-),1.56-1.59(m,1H,CH 3 -CH-CH-),1.54-1.57(m,2H,-CH -CH 2 -CH 3 ),1.30-1.40(m,6H,-CH 3 ),1.02-1.19(m,12H,-CH 3 ),0.81-0.92(m,6H,-CH 3 ).
化合物5o：1H NMR(DMSO-d6,δ/ppm,400MHz):7.43(dd,J＝20.0,12.0Hz,1H,Ph-H),7.08(d,J＝8.0Hz,2H,Ph-H),5.88(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.78(dd,J＝16.0,12.0Hz,1H,-CH-CH＝C-C＝C-),5.63(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.31(s,1H,-OH),5.25(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH2-),5.09(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),5.01-5.04(m,2H,-O-CH2-CH3),4.72-4.89(m,1H,-CH-O-C＝O-),4.72(t,J＝3.2Hz,2H,-O-CH-CH2-),4.58(d,J＝16.0Hz,1H,-CH-),4.46(d,J＝12.0Hz,1H,-CH-),4.10(s,1H,-OH),3.91-4.06(m,1H,CH3-CH-),3.91(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.77(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.64(d,J＝4.4Hz,1H,-CH-CH-O-),3.56-3.58(m,1H,CH3-CH-),3.54-3.55(m,1H,CH3-CH-O-),3.47-3.54(m,1H,-CH-CH-CH2-),3.37(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.33(s,3H,-O-CH3),3.31(s,3H,-O-CH3),3.21-3.24(m,1H,-CH-CH-CH2-),3.14(d,J＝8.0Hz,1H,-C-CH-CH-),3.08(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.91(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.71(m,1H,-CH-CH3),2.51(d,J＝3.6Hz,1H,-CH-CH-),2.31-2.62(m,2H,-CH2-C＝N-),2.17-2.30(m,2H,-C＝CH-CH2-CH-),1.96-2.17(m,2H,-CH-CH2-),1.73-2.15(m,4H,-CH-CH2-CH-),1.73-1.99(m,2H,-CH-CH2-CH-),1.60-1.67(m,1H,CH3-CH-CH-),1.50-1.54(m,2H,-CH-CH2-CH3),1.37-1.48(m,6H,-CH3),1.02-1.24(m,12H,-CH3),0.87-0.92(m,6H,-CH3).Compound 5o: 1 H NMR (DMSO-d 6 , δ/ppm, 400MHz): 7.43 (dd, J＝20.0, 12.0Hz, 1H, Ph-H), 7.08 (d, J＝8.0Hz, 2H, Ph- H),5.88(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.78(dd,J＝16.0,12.0Hz,1H,-CH-CH＝CC＝C-), 5.63(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.31(s,1H,-OH),5.25(dd,J＝12.0,9.2Hz,1H,-C＝CH -CH 2 -),5.09(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),5.01-5.04(m,2H,-O-CH 2 -CH 3 ),4.72 -4.89(m,1H,-CH-OC＝O-),4.72(t,J＝3.2Hz,2H,-O-CH-CH 2 -),4.58(d,J＝16.0Hz,1H,-CH -),4.46(d,J＝12.0Hz,1H,-CH-),4.10(s,1H,-OH),3.91-4.06(m,1H,CH 3 -CH-),3.91(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.77(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.64(d, J＝4.4Hz,1H,-CH-CH-O-),3.56-3.58(m,1H,CH 3 -CH-),3.54-3.55(m,1H,CH 3 -CH-O-),3.47- 3.54(m,1H,-CH-CH-CH 2 -),3.37(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.33(s,3H,-O-CH 3 ) ,3.31(s,3H,-O-CH 3 ),3.21-3.24(m,1H,-CH-CH-CH 2 -),3.14(d,J＝8.0Hz,1H,-C-CH-CH-),3.08(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.91(dd ,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.63-2.71(m,1H,-CH-CH 3 ),2.51(d,J＝3.6Hz,1H,-CH-CH- ),2.31-2.62(m,2H,-CH 2 -C＝N-),2.17-2.30(m,2H,-C＝CH-CH 2 -CH-),1.96-2.17(m,2H,-CH -CH 2 -),1.73-2.15(m,4H,-CH-CH 2 -CH-),1.73-1.99(m,2H,-CH-CH 2 -CH-),1.60-1.67(m,1H,CH 3 -CH-CH-),1.50-1.54(m,2H,-CH -CH 2 -CH 3 ),1.37-1.48(m,6H,-CH 3 ),1.02-1.24(m,12H,-CH 3 ),0.87-0.92(m,6H,-CH 3 ).
化合物5p：1H NMR(DMSO-d6,δ/ppm,400MHz):7.45(d,J＝8.0Hz,2H,Ph-H),7.28(d,J＝8.0Hz,2H,Ph-H),5.89(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.78(dd,J＝16.0,12.0Hz,1H,-CH-CH＝C-C＝C-),5.65(dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.37(s,1H,-OH),5.26(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH2-),5.13(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),5.05-5.09(m,2H,-O-CH2-CH3),4.81-4.87(m,1H,-CH-O-C＝O-),4.73(t,J＝3.2Hz,2H,-O-CH-CH2-),4.60(d,J＝16.0Hz,1H,-CH-),4.47(d,J＝12.0Hz,1H,-CH-),4.11(s,1H,-OH),4.01-4.06(m,1H,CH3-CH-),3.92(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.78(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.64(d,J＝4.4Hz,1H,-CH-CH-O-),3.57-3.59(m,1H,CH3-CH-),3.54-3.55(m,1H,CH3-CH-O-),3.47-3.54(m,1H,-CH-CH-CH2-),3.39(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.34(s,3H,-O-CH3),3.32(s,3H,-O-CH3),3.21-3.26(m,1H,-CH-CH-CH2-),3.14(d,J＝8.0Hz,1H,-C-CH-CH-),3.09(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.91(dd,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.64-2.71(m,1H,-CH-CH3),2.52(d,J＝3.6Hz,1H,-CH-CH-),2.36-2.63(m,2H,-CH2-C＝N-),2.21-2.34(m,2H,-C＝CH-CH2-CH-),1.87-2.21(m,2H,-CH-CH2-),1.74-2.16(m,4H,-CH-CH2-CH-),1.74-1.99(m,2H,-CH-CH2-CH-),1.60-1.67(m,1H,CH3-CH-CH-),1.50-1.54(m,2H,-CH-CH2-CH3),1.47-1.49(m,6H,-CH3),1.11-1.20(m,12H,-CH3),0.83-0.92(m,6H,-CH3).Compound 5p: 1 H NMR (DMSO-d 6 , δ/ppm, 400MHz): 7.45 (d, J = 8.0 Hz, 2H, Ph-H), 7.28 (d, J = 8.0 Hz, 2H, Ph-H) ,5.89(dd,J＝14.8,12.4Hz,1H,-C＝CH-C＝C),5.78(dd,J＝16.0,12.0Hz,1H,-CH-CH＝CC＝C-),5.65( dd,J＝14.4,9.6Hz,1H,-C＝CH-C＝C),5.37(s,1H,-OH),5.26(dd,J＝12.0,9.2Hz,1H,-C＝CH-CH 2 -),5.13(br,1H,-OH),5.04(d,J＝4.0Hz,1H,-CH＝C-),5.05-5.09(m,2H,-O-CH 2 -CH 3 ),4.81 -4.87(m,1H,-CH-OC＝O-),4.73(t,J＝3.2Hz,2H,-O-CH-CH 2 -),4.60(d,J＝16.0Hz,1H,-CH -),4.47(d,J＝12.0Hz,1H,-CH-),4.11(s,1H,-OH),4.01-4.06(m,1H,CH 3 -CH-),3.92(d,J＝2.8Hz,1H,-C＝C-CH-OH),3.78(dd,J＝9.2,6.4Hz,1H,-CH-CH-),3.64(d, J＝4.4Hz,1H,-CH-CH-O-),3.57-3.59(m,1H,CH 3 -CH-),3.54-3.55(m,1H,CH 3 -CH-O-),3.47- 3.54(m,1H,-CH-CH-CH 2 -),3.39(dd,J＝14.4,9.6Hz,1H,-CH-CH-CH-),3.34(s,3H,-O-CH 3 ) ,3.32(s,3H,-O-CH 3 ),3.21-3.26(m,1H,-CH-CH-CH 2 -),3.14(d,J＝8.0Hz,1H,-C-CH-CH-),3.09(d,J＝14.4Hz,1H,-C＝O-CH-CH＝C-),2.91(dd ,J＝14.8,8.8Hz,1H,-CH-CH-CH-),2.64-2.71(m,1H,-CH-CH 3 ),2.52(d,J＝3.6Hz,1H,-CH-CH- ),2.36-2.63(m,2H,-CH 2 -C＝N-),2.21-2.34(m,2H,-C＝CH-CH 2 -CH-),1.87-2.21(m,2H,-CH -CH 2 -),1.74-2.16(m,4H,-CH-CH 2 -CH-),1.74-1.99(m,2H,-CH-CH 2 -CH-),1.60-1.67(m,1H,CH 3 -CH-CH-),1.50-1.54(m,2H,-CH -CH 2 -CH 3 ),1.47-1.49(m,6H,-CH 3 ),1.11-1.20(m,12H,-CH 3 ),0.83-0.92(m,6H,-CH 3 ).
实施例2Example 2
用浸叶法测试目标化合物对小菜蛾的杀小菜蛾活性。The activity of the target compounds against Plutella xylostella was tested by leaf dip method.
浸叶法：挑选大小基本一致、健康的3龄小菜蛾供试，用镊子夹住3龄小菜蛾幼虫，在配好的各个浓度的药液中，将试虫浸泡5秒，之后再放置在铺有滤纸的直径9厘米的培养皿中，在每个直径为9cm的培养皿中加入新鲜的等量的甘蓝叶片。一次试验用10头供试粘虫。处理后将培养皿移入温度为27℃、湿度为75％的养虫室内培养。分别在24h、48h后记录供试小菜蛾的死亡数，通过计算校正死亡率来检测化合物的杀小菜蛾活性。Leaf dipping method: Select healthy 3rd-instar diamondback moths of basically the same size for testing, clamp the 3rd-instar diamondback moth larvae with tweezers, soak the test insects in the prepared drug solution of various concentrations for 5 seconds, and then place them in a 9-cm diameter culture dish covered with filter paper. Add an equal amount of fresh cabbage leaves to each 9-cm diameter culture dish. Use 10 test sticky insects for one test. After treatment, move the culture dish into an insect breeding room with a temperature of 27°C and a humidity of 75% for cultivation. Record the number of deaths of the test diamondback moths after 24h and 48h, respectively, and detect the activity of the compound in killing diamondback moths by calculating the corrected mortality rate.
化合物5a～5p的杀虫活性列于表2中。The insecticidal activities of compounds 5a to 5p are listed in Table 2.
表2化合物5a～5p的杀小菜蛾活性Table 2 Activity of compounds 5a-5p against Plutella xylostella
从表2可以看出化合物5b、5d、5e、5g、5k、5m、5p的杀小菜蛾活性均超过了AVM B2a，尤其是化合物5b和5p，在施药浓度1mg/kg浓度下，杀小菜蛾活性高达100％。It can be seen from Table 2 that the activity of compounds 5b, 5d, 5e, 5g, 5k, 5m and 5p in killing Plutella xylostella exceeds that of AVM B 2a , especially compounds 5b and 5p, which have an activity of killing Plutella xylostella as high as 100% at an application concentration of 1 mg/kg.
实施例3Example 3
用叶螨叶碟喷雾法测试目标化合物对朱砂叶螨成螨、幼螨及螨卵的活性。The activity of the target compounds against adults, larvae and eggs of Tetranychus cinnabarinus was tested by leaf-disc spray method.
叶螨叶碟喷雾法：选取生长一致的蚕豆叶片，用打孔器做成叶碟，每皿2个叶碟，在培养皿内放置湿海绵，其上放滤纸，滤纸放叶碟。将室内饲养的叶螨成螨(幼螨)接种到准备好的其中1个叶碟上，每叶碟5～10头，让其产卵24h后剔除成螨；次日在另一叶片上接种成螨15～20头，让其产卵24h，这样可以得到成螨、48h幼螨、螨卵三种供试螨态。药剂处理前记录基数，采用POTTER喷雾塔进行处理，每处理喷药液量为1mL。定时进行调查，分别记载各处理的死活螨数，通过计算校正死亡率来检测化合物的杀螨活性。Leaf disc spray method for spider mites: Select broad bean leaves with consistent growth, use a hole puncher to make leaf discs, 2 leaf discs per dish, place a wet sponge in the culture dish, put filter paper on it, and put leaf discs on the filter paper. Inoculate the adult spider mites (young mites) raised indoors on one of the prepared leaf discs, 5 to 10 per leaf disc, let them lay eggs for 24 hours and then remove the adult mites; the next day, inoculate 15 to 20 adult mites on another leaf and let them lay eggs for 24 hours, so that three types of mites can be obtained for testing: adult mites, 48-hour young mites, and mite eggs. Record the base number before the treatment with the agent, use a POTTER spray tower for treatment, and spray 1 mL of liquid for each treatment. Conduct investigations regularly, record the number of dead and alive mites in each treatment, and detect the acaricidal activity of the compound by calculating the corrected mortality rate.
化合物5a～5p的杀螨活性列于表3中。The acaricidal activities of compounds 5a to 5p are listed in Table 3.
表3化合物5a～5p的杀朱砂叶螨活性Table 3 Activity of compounds 5a-5p against Tetranychus cinnabarinus
从表3可以看出化合物5b、5e、5g、5k、5l和5m的杀成螨活性优于AVM B2a；化合物5b、5e、5g、5h、5j、5k、5l、5m、5n、5o和5p的杀幼螨活性优于AVM B2a；化合物5b、5e、5g、5h、5k、5l、5m、5n、5o和5p的杀螨卵活性优于AVM B2a，特别是超过了成药AVM。It can be seen from Table 3 that the adult mite killing activity of compounds 5b, 5e, 5g, 5k, 5l and 5m is better than AVM B 2a ; the larval mite killing activity of compounds 5b, 5e, 5g, 5h, 5j, 5k, 5l, 5m, 5n, 5o and 5p is better than AVM B 2a ; the mite egg killing activity of compounds 5b, 5e, 5g, 5h, 5k, 5l, 5m, 5n, 5o and 5p is better than AVM B 2a , especially exceeding the drug AVM.
实施例4Example 4
采用触杀法测试目标化合物对松材线虫的杀线虫活性。The contact killing method was used to test the nematicidal activity of the target compounds against pine wood nematodes.
触杀法：采用触杀法，把各种待测化合物配制成一定的质量浓度，同时将10μL不同质量浓度的待测化合物和90μL线虫悬浮液(1000条/mL)加入试管，震动混合均匀以后，放置到25℃条件下培养，24、48h后，在显微镜下检查线虫的存活情况，统计线虫死亡率。Contact killing method: Using the contact killing method, various test compounds were prepared into a certain mass concentration, and 10 μL of the test compounds with different mass concentrations and 90 μL of nematode suspension (1000/mL) were added to the test tube. After shaking and mixing evenly, they were placed at 25°C for cultivation. After 24 and 48 hours, the survival of the nematodes was checked under a microscope, and the nematode mortality rate was calculated.
化合物5a～5e的杀线虫活性列于表4中。The nematicidal activities of compounds 5a-5e are listed in Table 4.
表4化合物5a～5e在10mg/L浓度下的杀线虫活性Table 4 Nematicidal activity of compounds 5a-5e at a concentration of 10 mg/L
从表4可以看出在10mg/L浓度下，化合物5b、5c、5d、5e的杀线虫活性均超过60％，尤其是产物5b的杀线虫活性达到75％，超过了AVM B2a。It can be seen from Table 4 that at a concentration of 10 mg/L, the nematicidal activities of compounds 5b, 5c, 5d, and 5e all exceeded 60%, and in particular, the nematicidal activity of product 5b reached 75%, exceeding that of AVM B 2a .
以上所述活性化合物仅为本发明可行实施的穷举。对于本领域一般技术人员而言，对其所做出的任何显而易见的改动，都应当被认为包含在本发明的权利要求保护范围之内。The active compounds described above are only an exhaustive list of the feasible implementations of the present invention. Any obvious changes made to them by a person skilled in the art should be considered to be included in the scope of protection of the claims of the present invention.
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| US4849446A (en) * | 1986-09-12 | 1989-07-18 | American Cyanamid Company | 23-imino derivatives of 23-keto compounds |
| US5015630A (en) * | 1989-01-19 | 1991-05-14 | Merck & Co., Inc. | 5-oxime avermectin derivatives |
| CN107266511A (en) * | 2017-07-25 | 2017-10-20 | 中国农业大学 | Novel compound of 5 oxime ester B2a structures of one class and preparation method and application |
| CN109851648A (en) * | 2019-01-11 | 2019-06-07 | 南开大学 | A kind of synthesis and application of derivative of macrolides |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4849446A (en) * | 1986-09-12 | 1989-07-18 | American Cyanamid Company | 23-imino derivatives of 23-keto compounds |
| US5015630A (en) * | 1989-01-19 | 1991-05-14 | Merck & Co., Inc. | 5-oxime avermectin derivatives |
| CN107266511A (en) * | 2017-07-25 | 2017-10-20 | 中国农业大学 | Novel compound of 5 oxime ester B2a structures of one class and preparation method and application |
| CN109851648A (en) * | 2019-01-11 | 2019-06-07 | 南开大学 | A kind of synthesis and application of derivative of macrolides |
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| Title |
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| Synthesis, bioactivities and 3D-QSAR of novel avermectin B2a aglycon derivatives;Fangfang Huang et al.;《Chinese Chemical Letters》;20190329;第31卷;第141-144页 * |
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