CN113004111A - 一种合成(r)-梨木虱性信息素的方法 - Google Patents
一种合成(r)-梨木虱性信息素的方法 Download PDFInfo
- Publication number
- CN113004111A CN113004111A CN202110180056.XA CN202110180056A CN113004111A CN 113004111 A CN113004111 A CN 113004111A CN 202110180056 A CN202110180056 A CN 202110180056A CN 113004111 A CN113004111 A CN 113004111A
- Authority
- CN
- China
- Prior art keywords
- reaction
- methyl
- sex pheromone
- psyllid
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000877 Sex Attractant Substances 0.000 title claims abstract description 22
- 238000000034 method Methods 0.000 title claims abstract description 14
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 68
- -1 Oxazolidinone amide Chemical class 0.000 claims abstract description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims abstract description 10
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 claims abstract description 10
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Substances C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims abstract description 7
- CLFMEEYUFHPNBC-MUUNZHRXSA-N (13r)-13-methylheptacosane Chemical compound CCCCCCCCCCCCCC[C@H](C)CCCCCCCCCCCC CLFMEEYUFHPNBC-MUUNZHRXSA-N 0.000 claims abstract description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 5
- 150000004714 phosphonium salts Chemical group 0.000 claims abstract description 5
- 239000012279 sodium borohydride Substances 0.000 claims abstract description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 claims abstract description 5
- RNHWYOLIEJIAMV-UHFFFAOYSA-N 1-chlorotetradecane Chemical compound CCCCCCCCCCCCCCCl RNHWYOLIEJIAMV-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 238000007239 Wittig reaction Methods 0.000 claims abstract description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims abstract description 3
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims abstract description 3
- 230000006698 induction Effects 0.000 claims abstract description 3
- 241001466030 Psylloidea Species 0.000 abstract description 6
- 230000003321 amplification Effects 0.000 abstract description 3
- 238000003199 nucleic acid amplification method Methods 0.000 abstract description 3
- 239000000575 pesticide Substances 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 28
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 19
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
- 239000012043 crude product Substances 0.000 description 16
- 239000012074 organic phase Substances 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 14
- 238000010898 silica gel chromatography Methods 0.000 description 13
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical class O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- CGTBUYCHHZHYBU-OAHLLOKOSA-N (2R)-2-methyltetradecan-1-ol Chemical compound CCCCCCCCCCCC[C@@H](C)CO CGTBUYCHHZHYBU-OAHLLOKOSA-N 0.000 description 8
- YAXLAWVBFXKNFQ-OAHLLOKOSA-N BrC[C@@H](CCCCCCCCCCCC)C Chemical compound BrC[C@@H](CCCCCCCCCCCC)C YAXLAWVBFXKNFQ-OAHLLOKOSA-N 0.000 description 8
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- XBKRGWZGHMTCJW-VNUFCWELSA-M [Br-].C[C@@H](C[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1)CCCCCCCCCCCC Chemical compound [Br-].C[C@@H](C[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1)CCCCCCCCCCCC XBKRGWZGHMTCJW-VNUFCWELSA-M 0.000 description 7
- 229910052786 argon Inorganic materials 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- NEHNMFOYXAPHSD-SNVBAGLBSA-N (+)-Citronellal Chemical compound O=CC[C@H](C)CCC=C(C)C NEHNMFOYXAPHSD-SNVBAGLBSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- UGEPWPBOWVDPCK-MUUNZHRXSA-N C[C@@H](C=CCCCCCCCCCCCC)CCCCCCCCCCCC Chemical compound C[C@@H](C=CCCCCCCCCCCCC)CCCCCCCCCCCC UGEPWPBOWVDPCK-MUUNZHRXSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000007832 Na2SO4 Substances 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- NEHNMFOYXAPHSD-UHFFFAOYSA-N citronellal group Chemical group CC(CC=O)CCC=C(C)C NEHNMFOYXAPHSD-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- BGEHHAVMRVXCGR-UHFFFAOYSA-N tridecanal Chemical compound CCCCCCCCCCCCC=O BGEHHAVMRVXCGR-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 235000014443 Pyrus communis Nutrition 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000007810 chemical reaction solvent Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
- 150000003333 secondary alcohols Chemical class 0.000 description 3
- LPWCRLGKYWVLHQ-UHFFFAOYSA-N tetradecanoyl chloride Chemical compound CCCCCCCCCCCCCC(Cl)=O LPWCRLGKYWVLHQ-UHFFFAOYSA-N 0.000 description 3
- CLFMEEYUFHPNBC-UHFFFAOYSA-N 13-methylheptacosane Chemical compound CCCCCCCCCCCCCCC(C)CCCCCCCCCCCC CLFMEEYUFHPNBC-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 240000001987 Pyrus communis Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 238000003328 mesylation reaction Methods 0.000 description 2
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- OJOFMLDBXPDXLQ-SECBINFHSA-N (4r)-4-benzyl-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N[C@@H]1CC1=CC=CC=C1 OJOFMLDBXPDXLQ-SECBINFHSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 235000015001 Cucumis melo var inodorus Nutrition 0.000 description 1
- 240000002495 Cucumis melo var. inodorus Species 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 241000526145 Psylla Species 0.000 description 1
- 241000220324 Pyrus Species 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- IFQPKTPQJLAZHQ-UHFFFAOYSA-M [Br-].CCCCCCCCC[Mg+] Chemical compound [Br-].CCCCCCCCC[Mg+] IFQPKTPQJLAZHQ-UHFFFAOYSA-M 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229930003633 citronellal Natural products 0.000 description 1
- 235000000983 citronellal Nutrition 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 1
- 238000006735 epoxidation reaction Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 210000002149 gonad Anatomy 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- CWTPEXDGZPTZSH-UHFFFAOYSA-M magnesium;decane;bromide Chemical compound [Mg+2].[Br-].CCCCCCCCC[CH2-] CWTPEXDGZPTZSH-UHFFFAOYSA-M 0.000 description 1
- MBHQEXPGNCWWBP-UHFFFAOYSA-M magnesium;dodecane;bromide Chemical compound [Mg+2].[Br-].CCCCCCCCCCC[CH2-] MBHQEXPGNCWWBP-UHFFFAOYSA-M 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000003016 pheromone Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C5/00—Preparation of hydrocarbons from hydrocarbons containing the same number of carbon atoms
- C07C5/02—Preparation of hydrocarbons from hydrocarbons containing the same number of carbon atoms by hydrogenation
- C07C5/03—Preparation of hydrocarbons from hydrocarbons containing the same number of carbon atoms by hydrogenation of non-aromatic carbon-to-carbon double bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
- C07C1/32—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen
- C07C1/34—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen reacting phosphines with aldehydes or ketones, e.g. Wittig reaction
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/16—Preparation of halogenated hydrocarbons by replacement by halogens of hydroxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/147—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
- C07D263/26—Oxygen atoms attached in position 2 with hetero atoms or acyl radicals directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/54—Quaternary phosphonium compounds
- C07F9/5442—Aromatic phosphonium compounds (P-C aromatic linkage)
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2523/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group C07C2521/00
- C07C2523/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group C07C2521/00 of noble metals
- C07C2523/40—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group C07C2521/00 of noble metals of the platinum group metals
- C07C2523/44—Palladium
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明属于绿色农药技术领域，公开了一种新的合成(R)‑梨木虱性信息素的方法。该方法以正十四酸1为起始原料，先与草酰氯反应生成正十四酰氯，再与(R)‑4‑苄基‑2‑噁唑烷酮反应生成
唑烷酮酰胺2。接着在NaHMDS存在下与CH3I反应生成多一个甲基的
唑烷酮酰胺3，再经硼氢化钠还原为手性醇4。然后经溴代、与PPh3反应生成季鏻盐6，最后经Wittig反应与催化氢化，制得(R)‑梨木虱性信息素，即(R)‑13‑甲基二十七烷。本发明利用Evans手性诱导法构建手性甲基，具有合成路线简捷、反应条件温和、易于放大等优势。
Description
技术领域
本发明涉及绿色农药技术领域，具体涉及一种新的合成(R)-梨木虱性信息素的方法。
背景技术
梨木虱(Cacopsylla pyricola)是危害梨树的重要害虫，主要吸取梨树嫩绿组织的汁液，分泌蜜露诱发煤污病，影响梨的品质与产量(闫文涛；张怀江；岳强；仇贵生；孙丽娜；王雅偲.果树实用技术与信息2020,31.Horton,D.R.；Cooper,W.R.J.Insect.Sci.2017,17,1.)。梨木虱性信息素由成虫雌蛾的性腺体分泌、释放，具有引诱雄虫的生理活性(Victoria Soroker,S.T.,Ally R.et al J.Insect.Behav.2004,17,613)。2009年，Guédot等首次鉴定出梨木虱性信息素的主要活性成分为13-甲基二十七烷，而且人工合成的外消旋体对梨木虱雄虫具有引诱作用(Guedot,C；Millar,J.G.；Horton,D.R.；Landolt,P.J.J.Chem.Ecol.2009,35,1437.)。昆虫性信息素是一类极具发展前景的绿色农药，而且其绝对构型是影响其生物活性的关键因素(Melnik,K.；Grimm,C.；Wittbrodt,J.；Ruther,J.；Schulz,S.Org.Biomol.Chem.2020,18,3463.)。因此，研究(R)-梨木虱性信息素(式1)的合成具有重要的意义。目前，文献报道的制备(R)-梨木虱性信息素的方法只有香茅醛手性原料法。
(1)2001年，Mori等以(R)-香茅醛为起始原料，先还原为醇，再与对甲苯磺酰氯反应生成对甲苯磺酸酯，然后与正十二烷基溴化镁发生偶联反应延长碳链，接着经四氧化锇氧化、高碘酸氧化得到醛，再与正壬基溴化镁反应制得仲醇，最后经甲磺酰化与还原得到目标产物(R)-梨木虱性信息素(Marukawa,K.；Takikawa,H.；Mori,K.Biosci.,Biotechnol.,Biochem.2001,65,305.)。
(2)2011年，Mori以(R)-香茅醛为起始原料，先与正癸基溴化镁生成仲醇，然后经甲磺酰化与四氢铝锂还原除去仲羟基，再经环氧化与高碘酸氧化得到醛，接着与十一烷基格氏试剂反应得到碳链延长的仲醇，最后经甲磺酰化与四氢铝锂还原除去仲羟基，制得目标产物(R)-梨木虱性信息素(Mori,K.Tetrahedron:Asymmetry 2011,22,1006.)。
虽然已有文献报道(R)-梨木虱性信息素的合成研究，但存在路线冗长、反应条件苛刻、反应步骤繁琐、难于放大等诸多问题，因此，化学工作者需要发展新的、对环境友好的、简捷高效的、易于放大的合成(R)-梨木虱性信息素的方法。
发明内容
本发明旨在提供一种新的合成(R)-梨木虱性信息素的方法。本发明以正十四酸1为起始原料，先与草酰氯反应生成正十四酰氯，再与(R)-4-苄基-2-噁唑烷酮反应生成
唑烷酮酰胺2。接着在NaHMDS存在下与CH3I反应生成多一个甲基的
唑烷酮酰胺3，再经硼氢化钠还原为手性醇4。然后经溴代、与PPh3反应生成季鏻盐6，最后经Wittig反应与催化氢化，制得(R)-梨木虱性信息素，即(R)-13-甲基二十七烷。本发明利用Evans手性诱导法构建手性甲基，具有合成路线简捷、反应条件温和、易于放大等优势。本发明合成(R)-梨木虱性信息素的合成路线参见式2。
本发明合成(R)-13-甲基二十七烷的方法包括如下步骤。
(1)(R)-4-苄基-3-正十四酰基
唑烷酮(2)的合成
0℃下，在DCM、正十四酸2与催化量的DMF的混合液中，逐滴加入草酰氯，反应1h，TLC监测反应完全后，停止反应。减压除去反应溶剂得到正十四酰氯粗品。
0℃下，在THF与(R)-4-苄基-2-噁唑烷酮混合溶液中，分批加入氢化钠，搅拌2h。室温下加入正十四酰氯粗品，搅拌反应3h。TLC监测反应完全后，停止反应。用饱和NH4Cl溶液淬灭反应，分液。水相用乙醚萃取，合并有机相。有机相经洗涤、干燥与减压浓缩，最后经硅胶柱色谱纯化制得(R)-4-苄基-3-正十四酰基
唑烷酮(2)。
(2)(R)-4-苄基-3-((R)-2-甲基正十四酰基)
唑烷酮(3)的合成
氩气保护下，将
唑烷酮酰胺2溶于无水THF，降温至-78℃，缓慢滴加NaHMDS，搅拌1h。缓慢滴加碘甲烷，搅拌反应3h。TLC监测反应完全后，停止反应。用饱和NH4Cl溶液淬灭反应，分液。水相用乙酸乙酯萃取，合并有机相。有机相经洗涤、干燥与减压浓缩，最后经硅胶柱色谱纯化制得(R)-4-苄基-3-((R)-2-甲基正十四酰基)
唑烷酮(3)。
(3)(R)-2-甲基-1-十四醇(4)的合成
0℃下，将硼氢化钠水溶液滴入
唑烷酮酰胺3的THF溶液，升温至室温，反应3h。TLC监测反应完全后，停止反应。用2.5M盐酸调节pH＝6，分液。水层用乙酸乙酯萃取，合并有机相。有机相经洗涤、干燥与减压浓缩，最后经硅胶柱色谱纯化制得(R)-2-甲基-1-十四醇(4)。
(4)(R)-2-甲基-1-溴十四烷(5)的合成
氩气保护下，0℃下在手性醇4的DCM溶液中，加入PPh3的DCM溶液，再滴入CBr4的DCM溶液。升温至室温，反应12h。TLC监测反应完全后，停止反应。减压浓缩，加入正己烷，过滤。将滤液浓缩，最后经硅胶柱色谱纯化制得(R)-2-甲基-1-溴十四烷(5)。
(5)(R)-溴化三苯基2-甲基-1-十四烷基鏻(6)的合成
氩气保护下，室温下向溴代物5的乙腈溶液，加入PPh3的乙腈溶液，加热回流反应24h。TLC监测反应完全后，停止反应。减压浓缩除去溶剂，最后经硅胶柱色谱纯化制得(R)-溴化三苯基2-甲基-1-十四烷基鏻(6)。
(6)(R)-梨木虱性信息素的合成
氩气保护下，室温下向季鏻盐6的1,2-二甲氧基乙烷溶液，滴入n-BuLi溶液。搅拌反应2h，得到鏻叶立德混合液。降温至-40℃，加入正十三醛的1,2-二甲氧基乙烷溶液。升温至室温，反应5h。TLC监测反应完全后，停止反应。用饱和NH4Cl溶液淬灭反应，分液，乙醚萃取，合并有机相。有机相经洗涤、干燥与减压浓缩，最后经硅胶柱色谱纯化制得(R)-15-甲基-13-二十七碳烯。
在氢气体系中，室温下加入钯碳，再加入(R)-15-甲基-13-二十七碳烯的乙醇溶液与催化剂量的冰醋酸，搅拌反应12h。TLC监测反应完全后，停止反应。过滤，滤液减压浓缩。最后经硅胶柱色谱纯化制得(R)-梨木虱性信息素，即(R)-13-甲基二十七烷。
具体实施方式
实施例1
(R)-4-苄基-3-正十四酰基
唑烷酮(2)的合成
0℃下，在100mL三口瓶中依次加入DCM(20mL)、正十四酸1(2.28g，10mmol)与3-5滴DMF，混合均匀。然后缓慢滴入草酰氯(1.90g，15mmol)。在0℃下继续搅拌反应1h。TLC监测反应完全后，停止反应。减压浓缩除去反应溶剂，得到浅黄色固体正十四酰氯粗品。
室温下，在100mL三口瓶中依次加入THF(20mL)与(R)-4-苄基
唑烷酮(1.45g，8.25mmol)，搅拌均匀。在0℃下缓慢加入氢化钠(0.50g，质量分数为60％，12.3mmol)，将混合液升温至室温，搅拌反应2h。室温下加入正十四酰氯粗品，继续搅拌反应3h。TLC监测反应完全后，停止反应。用饱和NH4Cl溶液(10mL)淬灭反应，分液。水相用乙醚萃取(3×30mL)，合并有机相。有机相用饱和NaCl溶液(50mL)洗涤，无水Na2SO4干燥，减压浓缩得到粗产物。粗产物经硅胶柱色谱(石油醚/乙酸乙酯10:1)纯化，得到白色固体(R)-4-苄基-3-正十四酰基
唑烷酮(2)(2.99g,产率94％)。mp 58-59℃；[α]D 20＝–28.2(c＝2.14in CHCl3)；1H NMR(300MHz,CDCl3,δ):7.38–7.18(m,5H),4.68(ddt,J＝13.1,7.0,3.4Hz,1H),4.32–4.04(m,2H),3.31(dd,J＝13.3,3.3Hz,1H),3.03–2.71(m,3H),1.80–1.53(m,2H),1.35–1.27(m,20H),0.89(t,J＝6.7Hz,3H)；13C NMR(75MHz,CDCl3,δ):173.59,153.60,135.48,129.56,129.08,127.47,66.28,55.29,38.08,35.68,32.06,29.82,29.80,29.78,29.76,29.63,29.54,29.49,29.28,24.42,22.83,14.25；HRMS(ESI,m/z):[M+H]+calcd for C24H38O3N,388.2846；found,388.2829.
实施例2
(R)-4-苄基-3-((R)-2-甲基正十四酰基)
唑烷酮(3)的合成
氩气保护下，室温下在250mL三口瓶中加入
唑烷酮酰胺3(3.87g，10mmol)的THF溶液(80mL)。将溶液降温至-78℃，在15min内滴入NaHMDS(7.12mL,2.0M THF溶液,14.25mmol)，混合液搅拌1h。在78℃下，缓慢滴入碘甲烷(7.34g,3.22mL,52mmol)，继续搅拌反应3h。TLC监测反应完全后，停止反应。用饱和的NH4Cl溶液(75mL)淬灭反应，分液。水相用乙酸乙酯(3×75mL)萃取，合并有机相。有机相用饱和NaCl溶液(300mL)洗涤，无水Na2SO4干燥，减压浓缩得到粗产物。粗产物经过硅胶柱色谱(石油醚/乙酸乙酯10:1)纯化，得到白色固体(R)-4-苄基-3-((R)-2-甲基正十四酰基)
唑烷酮(3)(3.41g,产率85％)。mp 64-65℃；[α]D 20＝–40.4(c＝0.91in CHCl3)；1H NMR(300MHz,CDCl3,δ):7.42–7.13(m,5H),4.68(ddt,J＝10.0,6.7,3.3Hz,1H),4.29–4.07(m,2H),3.72–3.68(m,1H),3.28(dd,J＝13.3,3.3Hz,1H),2.77(dd,J＝13.3,9.6Hz,1H),1.84–1.65(m,1H),1.53–1.24(m,21H),1.23(d,J＝6.8Hz,3H),0.89(t,J＝6.7Hz,3H)；13C NMR(75MHz,CDCl3,δ):177.51,153.19,135.52,129.58,129.06,127.46,66.14,55.50,38.09,37.86,33.60,32.05,29.80,29.78,29.73,29.65,29.48,27.40,22.81,17.49,14.23；HRMS(ESI,m/z):[M+Na]+calcd for C25H39O3NNa,424.2822；found,424.2811.
实施例3
(R)-2-甲基-1-十四醇(4)的合成
室温下，在250mL三口瓶中加入
唑烷酮酰胺3(8.90g,22.16mmol)与THF(80mL)，搅拌溶解。冰浴冷却下，在30min内滴入硼氢化钠(3.35g,88.65mmol)水溶液(10mL)。将反应液温度升至室温，继续搅拌反应3h。TLC监测反应完全后，停止反应。用2.5M盐酸调节pH＝6，分液。水层用乙酸乙酯萃取(3×30mL)，合并有机相。有机相依次用饱和NaHCO3水溶液(20mL)与饱和NaCl溶液(20mL)洗涤，无水Na2SO4干燥，减压浓缩得到粗产物。粗产物经硅胶柱色谱(石油醚/乙酸乙酯5:1)纯化得到无色油状液体(R)-2-甲基-1-十四醇(4)(4.30g,产率85％,>99％ee)。[α]D 20＝+4.5(c＝1.68in CHCl3)；1H NMR(300MHz,CDCl3,δ):3.51(dd,J＝10.5,5.8Hz,1H),3.41(dd,J＝10.5,6.5Hz,1H),1.69–1.47(m,2H),1.42–1.17(m,22H),0.91(d,J＝6.0Hz,3H),0.87(t,J＝6.8Hz,3H)；13C NMR(75MHz,CDCl3,δ):68.56,35.92,33.31,32.07,30.10,29.82,29.80,29.50,27.14,22.83,16.72,14.24；HRMS(ESI,m/z)：[M+Na]+calcd for C15H32ONa,251.2345；found,251.2345.
实施例4
(R)-2-甲基-1-溴十四烷(5)的合成
氩气保护下，0℃下在250mL三口瓶中加入手性醇4(3.12g,13.64mmol)与DCM(20mL)，搅拌溶解。加入PPh3(5.37g,20.46mmol)的DCM溶液(20mL)，逐滴加入CBr4(6.78g,20.46mmol)的DCM溶液(20mL)。将反应液升温至室温，继续搅拌反应12h。TLC监测反应完全后，停止反应。减压浓缩除去溶剂，加入正己烷(100mL)。过滤，滤饼用正己烷(100mL)洗涤。将滤液减压浓缩得到粗产物。粗产物经硅胶柱色谱(石油醚)纯化，得到无色油状液体(R)-2-甲基-1-溴十四烷(5)(3.89g,产率98％)。[α]D 20＝+0.35(c＝2.3in CHCl3)；1H NMR(300MHz,CDCl3,δ):2.65(dd,J＝9.8,4.9Hz,1H),2.57(dd,J＝9.8,6.2Hz,1H),1.14–0.98(m,1H),0.72–0.51(m,22H),0.28(d,J＝6.6Hz,3H),0.16(t,J＝6.7Hz,3H)；13C NMR(75MHz,CDCl3,δ):41.67,35.39,35.06,32.09,29.87,29.81,29.79,29.74,29.51,27.04,22.85,18.95,14.25；HRMS(ESI,m/z):[M+H]+calcd for C15H32Br,291.1682；found,291.1726.
实施例5
(R)-溴化三苯基2-甲基-1-十四烷基鏻(6)的合成
氩气保护下，室温下在100mL三口瓶中加入溴代烷5(2.00g,6.87mmol)的乙腈溶液(20mL)，然后加入PPh3(2.70g,10.30mmol)的乙腈溶液(20mL)。将反应液加热至85℃，继续搅拌反应24h。TLC监测反应完全后，停止反应。减压浓缩除去反应溶剂，得到粗产物。粗产物经硅胶柱色谱(二氯甲烷/甲醇10:1)纯化，得到无色粘稠液体(R)-溴化三苯基2-甲基-1-十四烷基鏻(6)(1.90g,产率50％)。[α]D 20＝–0.68(c＝1.17in CHCl3)；1H NMR(400MHz,CDCl3,δ):8.20–6.87(m,15H),3.84–3.75(m,1H),3.50–3.26(m,1H),2.06–2.04(m,1H),1.79–1.01(m,22H),0.96(d,J＝6.5Hz,3H),0.80(t,J＝6.4Hz,3H)；13C NMR(126MHz,CDCl3,δ):135.07,135.05,133.72,133.64,130.60,130.50,119.24,118.56,38.20,38.13,31.92,29.66,29.64,29.62,29.57,29.50,29.35,29.30,26.78,22.69,21.13,21.07,14.14；HRMS(ESI,m/z):[M+H]+calcd for C33H47BrP,553.2593；found,553.2607.
实施例6
(R)-梨木虱性信息素的合成
氩气保护下，室温下在100mL三口瓶中加入季鏻盐6(2.72g,4.91mmol)与1,2-二甲氧基乙烷(30mL)，搅拌溶解，然后在30min内缓慢滴入正丁基锂(3.93mL,2.5M正己烷溶液,9.83mmol)。继续搅拌反应2h，得到鏻叶立德混合液。将混合液降温至-40℃，在30min内缓慢滴入正十三醛(1.46g,7.37mmol)的1,2-二甲氧基乙烷溶液(15mL)。将反应液缓慢升温至室温，继续搅拌反应5h。TLC监测反应完全后，停止反应。冰浴冷却下用饱和NH4Cl溶液(10mL)淬灭反应，分液。水层用乙醚萃取(3×20mL)，合并有机相。有机相用饱和NaCl水溶液(20mL)洗涤，无水Na2SO4干燥，减压浓缩得到粗产物。粗产物用硅胶柱色谱(石油醚)纯化，得到无色粘稠液体(R)-15-甲基-13-二十七碳烯(1.31g)。
室温下在100mL三口瓶中加入钯碳(0.50g，10％)，装上氢气球使反应体系充满H2。然后加入(R)-15-甲基-13-二十七碳烯(1.31g，3.33mmoL)的乙醇(20mL)溶液与3滴冰醋酸，继续搅拌反应12h。TLC监测反应完全后，停止反应。利用硅胶短柱除去固体，滤饼用石油醚(50mL)洗涤，将滤液减压浓缩得到粗产物。粗产物经硅胶柱色谱(正己烷)纯化，得到白色固体(R)-13-甲基二十七烷(1.29g,两步产率67％)。mp 29-30℃；[α]D 20＝–0.35(c＝2.27 inCHCl3)；1H NMR(300MHz,CDCl3,δ):1.45–1.02(m,49H),0.96–0.87(m,9H)；13C NMR(75MHz,CDCl3,δ):37.34,32.99,32.16,30.28,29.94,29.90,29.60,27.32,22.91,19.91,14.28；EIMS(m/z(％)):71(60),85(58),207(100),225(33),281(38).
Claims (1)
1.利用Evans手性诱导法合成(R)-梨木虱性信息素的一种新方法，其特征在于包括如下步骤：以正十四酸1为起始原料，先与草酰氯反应生成正十四酰氯，再与(R)-4-苄基-2-噁唑烷酮反应生成
唑烷酮酰胺2；接着在NaHMDS存在下与CH3I反应生成多一个甲基的
唑烷酮酰胺3，再经硼氢化钠还原为手性醇4；然后经溴代、与PPh3反应生成季鏻盐6，最后经Wittig反应与催化氢化，制得(R)-梨木虱性信息素，即(R)-13-甲基二十七烷；(R)-梨木虱性信息素的合成路线如下：
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110180056.XA CN113004111A (zh) | 2021-02-08 | 2021-02-08 | 一种合成(r)-梨木虱性信息素的方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110180056.XA CN113004111A (zh) | 2021-02-08 | 2021-02-08 | 一种合成(r)-梨木虱性信息素的方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113004111A true CN113004111A (zh) | 2021-06-22 |
Family
ID=76384060
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110180056.XA Pending CN113004111A (zh) | 2021-02-08 | 2021-02-08 | 一种合成(r)-梨木虱性信息素的方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113004111A (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114276205A (zh) * | 2021-11-25 | 2022-04-05 | 中国农业大学 | 一种合成(r)-11-甲基二十三烷的方法 |
| CN115417740A (zh) * | 2022-09-01 | 2022-12-02 | 石家庄学院 | 一种（r）-13-甲基二十七烷的制备方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6051590A (en) * | 1999-05-13 | 2000-04-18 | Merck & Co., Inc. | Immunosuppressant tricyclic compounds |
| CN102795997A (zh) * | 2012-08-21 | 2012-11-28 | 昆明博鸿生物科技有限公司 | 小菜蛾性信息素化合物的合成方法 |
-
2021
- 2021-02-08 CN CN202110180056.XA patent/CN113004111A/zh active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6051590A (en) * | 1999-05-13 | 2000-04-18 | Merck & Co., Inc. | Immunosuppressant tricyclic compounds |
| CN102795997A (zh) * | 2012-08-21 | 2012-11-28 | 昆明博鸿生物科技有限公司 | 小菜蛾性信息素化合物的合成方法 |
Non-Patent Citations (2)
| Title |
|---|
| MARUKAWA, KAORU等: "Synthesis of the enantiomers of some methyl-branched cuticular hydrocarbons of the ant, Diacamma sp", 《BIOSCIENCE, BIOTECHNOLOGY, AND BIOCHEMISTRY》 * |
| YANG, ZHICAI等: "Asymmetric Synthesis and Absolute Configuration of Streptophenazine G", 《JOURNAL OF ORGANIC CHEMISTRY》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114276205A (zh) * | 2021-11-25 | 2022-04-05 | 中国农业大学 | 一种合成(r)-11-甲基二十三烷的方法 |
| CN115417740A (zh) * | 2022-09-01 | 2022-12-02 | 石家庄学院 | 一种（r）-13-甲基二十七烷的制备方法 |
| CN115417740B (zh) * | 2022-09-01 | 2023-08-29 | 石家庄学院 | 一种（r）-13-甲基二十七烷的制备方法 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN113004111A (zh) | 一种合成(r)-梨木虱性信息素的方法 | |
| US5149838A (en) | Intermediates for substituted azetidinones useful as anti-inflammatory and antidegenerative agents | |
| Shi et al. | Ethyl 3-Fluoro-3-(tributylstannyl)-2-methoxyacrylate: Preparation and Palladium/Copper-Cocatalyzed Cross-Coupling Reactions as a Novel Route to. beta.-Fluoro-. alpha.-keto Acid Derivatives | |
| CN109456182B (zh) | (5z,7e)-十二碳-5,7-二烯-1-醇及其乙酸酯与丙酸酯的合成 | |
| CN110937985B (zh) | 一种姜酮酚的合成方法 | |
| CN113004223A (zh) | 一种合成(3z,6z,9s,10r)-9,10-环氧-3,6-二十一碳二烯的方法 | |
| Hansen et al. | A facile formal synthesis of volicitin | |
| US4233231A (en) | Novel vinyl-stannyl derivatives | |
| Yasumoto et al. | Isolation and absolute configuration determination of aliphatic sulfates as the Daphnia kairomones inducing morphological defense of a phytoplankton—Part 2 | |
| CN112079679B (zh) | 黄星天牛性信息素(r,z)-21-甲基-8-三十五碳烯不对称全合成方法 | |
| CN113336726A (zh) | 一种布瓦西坦中间体的制备方法 | |
| CN108440460B (zh) | 紫苏烯及其类似物的制备方法 | |
| CN111205184A (zh) | 一种合成(9z,12e)-十四碳-9,12-二烯-1-醇乙酸酯的方法 | |
| CN110105311B (zh) | 一种美国白蛾性信息素中间体的合成方法 | |
| JPH06256334A (ja) | シスウイスキーラクトンの製造方法 | |
| CN109699646B (zh) | 一种水稻螟虫信息素成分的制备方法 | |
| RU2794756C1 (ru) | Способ получения транс-миртановой кислоты | |
| CN113773172A (zh) | 一种合成地衣蛾性信息素及其非对映体的方法 | |
| CN108299491B (zh) | 3-双烷基化-2-吲哚酮衍生物及其制备方法 | |
| CN102320966B (zh) | 一种(s)-烯虫乙酯化合物的立体专一性合成方法 | |
| CN115710180A (zh) | 一种不对称合成木槿曼粉蚧性信息素的方法 | |
| CN1328271C (zh) | 一种合成β－碘代丁烯酸内酯的方法 | |
| KR100985251B1 (ko) | 디엘-무스콘의 신규 합성중간체 및 디-무스콘과 엘-무스콘의 분리 정제방법 | |
| JP3254746B2 (ja) | 末端アセチレン化合物およびその製造法 | |
| US4477388A (en) | Vinylstannyl derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20210622 |