CN116082351B - Synthesis method and application of photoaffinity probe reagent 3- (3-ethanol-3H-biaziridine) propiolactone - Google Patents
Synthesis method and application of photoaffinity probe reagent 3- (3-ethanol-3H-biaziridine) propiolactone Download PDFInfo
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- CN116082351B CN116082351B CN202310058437.XA CN202310058437A CN116082351B CN 116082351 B CN116082351 B CN 116082351B CN 202310058437 A CN202310058437 A CN 202310058437A CN 116082351 B CN116082351 B CN 116082351B
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- ethanol
- diazo
- propiolactone
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- biaziridine
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- VEZXCJBBBCKRPI-UHFFFAOYSA-N beta-propiolactone Chemical compound O=C1CCO1 VEZXCJBBBCKRPI-UHFFFAOYSA-N 0.000 title claims description 25
- 229960000380 propiolactone Drugs 0.000 title claims description 25
- 239000003153 chemical reaction reagent Substances 0.000 title abstract description 11
- 239000000523 sample Substances 0.000 title abstract description 11
- 238000001308 synthesis method Methods 0.000 title description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 72
- 238000006243 chemical reaction Methods 0.000 claims abstract description 34
- -1 (aziridine) propionic acid lactone Chemical class 0.000 claims abstract description 21
- 238000000034 method Methods 0.000 claims abstract description 18
- 239000007810 chemical reaction solvent Substances 0.000 claims abstract description 13
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 12
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims abstract description 9
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims abstract description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 47
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 4
- 235000019260 propionic acid Nutrition 0.000 claims description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 3
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- SQHSJJGGWYIFCD-UHFFFAOYSA-N (e)-1-diazonio-1-dimethoxyphosphorylprop-1-en-2-olate Chemical compound COP(=O)(OC)C(\[N+]#N)=C(\C)[O-] SQHSJJGGWYIFCD-UHFFFAOYSA-N 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 238000005265 energy consumption Methods 0.000 abstract description 3
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 19
- 150000001875 compounds Chemical class 0.000 description 16
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000004949 mass spectrometry Methods 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- 239000003208 petroleum Substances 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 229910004298 SiO 2 Inorganic materials 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 229940125904 compound 1 Drugs 0.000 description 7
- 238000010828 elution Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical class C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- 229940126214 compound 3 Drugs 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical class [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical group NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000004576 sand Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical group OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
- 125000000478 (4R)-4-hydroxy-L-argininium group Chemical group 0.000 description 2
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical group [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- 241000208125 Nicotiana Species 0.000 description 2
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- OJFKUJDRGJSAQB-UHFFFAOYSA-N TAK-632 Chemical compound C1=C(NC(=O)CC=2C=C(C=CC=2)C(F)(F)F)C(F)=CC=C1OC(C(=C1S2)C#N)=CC=C1N=C2NC(=O)C1CC1 OJFKUJDRGJSAQB-UHFFFAOYSA-N 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 229940125773 compound 10 Drugs 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 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 2
- FRYHCSODNHYDPU-UHFFFAOYSA-N ethanesulfonyl chloride Chemical compound CCS(Cl)(=O)=O FRYHCSODNHYDPU-UHFFFAOYSA-N 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 229940017219 methyl propionate Drugs 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 229940080818 propionamide Drugs 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- ISNKSXRJJVWFIL-UHFFFAOYSA-N (sulfonylamino)amine Chemical compound NN=S(=O)=O ISNKSXRJJVWFIL-UHFFFAOYSA-N 0.000 description 1
- 125000005999 2-bromoethyl group Chemical group 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- MUEOQEUSJMFYHV-UHFFFAOYSA-N 4-amino-1-methylpyrrole-2-carboxylic acid Chemical compound CN1C=C(N)C=C1C(O)=O MUEOQEUSJMFYHV-UHFFFAOYSA-N 0.000 description 1
- PADDNCJJHROILV-UHFFFAOYSA-N 6-methoxy-4-methylpyridin-3-amine Chemical compound COC1=CC(C)=C(N)C=N1 PADDNCJJHROILV-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- DUEPRVBVGDRKAG-UHFFFAOYSA-N carbofuran Chemical compound CNC(=O)OC1=CC=CC2=C1OC(C)(C)C2 DUEPRVBVGDRKAG-UHFFFAOYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- XDGCVWFBTHGKIV-UHFFFAOYSA-N n-(hydroxymethyl)-5-oxopyrrolidine-2-carboxamide Chemical compound OCNC(=O)C1CCC(=O)N1 XDGCVWFBTHGKIV-UHFFFAOYSA-N 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D229/00—Heterocyclic compounds containing rings of less than five members having two nitrogen atoms as the only ring hetero atoms
- C07D229/02—Heterocyclic compounds containing rings of less than five members having two nitrogen atoms as the only ring hetero atoms containing three-membered rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for synthesizing a photoaffinity probe reagent 3- (3-ethanol-3H-bis (aziridine) propionic acid lactone and its application, characterized by the following steps: adding 3,3-cyclopentadienyl - (3Hbis (aziridine)) -6-one and m-chloroperoxybenzoic acid in a molar ratio of 1:1 to 1.5 to a reaction solvent, dichloromethane is added to a reaction vessel, and (3-ethanol-3H-bis (aziridine) propionic acid lactone is obtained after complete reaction at a reaction temperature of room temperature to 50 ℃. It also discloses the synthesis of 3- (3-butyne-1-yl) -3H diazol-3-ethanol, 3- (2-butyne-1-yl) -3H diazol-3-ethanol, The methods of acetic acid-3H-diazoly-3-propionic acid, 3- (2-haloethyl) -3H-diazo-3-propionic acid, 3-ethanol-3H-diazoly-3-propionyl hydrazine, and 3-ethanol-3H-diazoly-3-propionyl hydrazine are described, The advantages are short synthesis time, low energy consumption, and high safety.
Description
Technical Field
The invention relates to a novel key intermediate of a photoaffinity probe reagent, in particular to a synthesis method and application of a photoaffinity probe reagent 3- (3-ethanol-3H-biaziridine) propiolactone.
Background
3- (3-Ethanol-3H-biaziridine) propiolactone, the specific structure is as follows:
(3-ethanol-3H-bisaziridine) propiolactone is an important intermediate for preparing 3- (3-butyn-1-yl) -3H-diazo-3-ethanol, and 3- (3-butyn-1-yl) -3H-diazo-3-ethanol is an important intermediate for preparing corresponding iodo-compound, carboxylic acid and amine photoaffinity covalent labeling probes, and no published patent or literature report related to the technical route is seen at present.
The literature on the preparation of 3- (3-butyn-1-yl) -3H-diazo-3-ethanol is mainly published ：(1)CN109810099A;(2)Angewandte Chemie-International Edition-2013-8551;(3)Bioorganic Chemistry-2021-104551;(4)WO2019/135816A2;(5)WO2019/23147A;(6)CN113061111A1.
The synthesis route reported in the above text is basically consistent, the ethyl acetoacetate is used as a starting material, 3- (3-butyn-1-yl) -3H-diazo-3-ethanol is prepared through 5 steps, the total yield is about 48%, and the route uses dangerous reagents such as benzene, lithium aluminum hydride and the like, so that the method has great influence on personal safety and environmental pollution during operation, and has long synthesis process time and high energy consumption.
Disclosure of Invention
The invention aims to solve the technical problem of providing a synthesis method of a photoaffinity probe reagent 3- (3-ethanol-3H-biaziridine) propiolactone, which has short synthesis process time, low energy consumption and high safety, and an application thereof.
The technical scheme adopted for solving the technical problems is as follows:
1. a method for synthesizing (3-ethanol-3H-biaziridine) propiolactone, which comprises the following steps: 3, 3-cyclopentylidene- (3H-bisaziridine) -6-one and m-chloroperoxybenzoic acid are mixed according to a molar ratio of 1: 1-1.5, adding methylene dichloride into a reaction solvent, adding the methylene dichloride into a reaction kettle, and obtaining (3-ethanol-3H-biaziridine) propiolactone after the reaction is completed at the reaction temperature of room temperature to 50 ℃.
Further, the molar ratio of the 3, 3-cyclopentylidene- (3H-bisaziridine) -6-one to the m-chloroperoxybenzoic acid is 1:1.2. on the premise of ensuring the completion of the reaction, the proportion of the m-chloroperoxybenzoic acid is reduced, so that the safety of the reaction can be improved, and the burden is relieved for subsequent post-treatment and purification.
Further, the reaction solvent is at least one of dichloromethane, N-dimethylformamide and 1, 4-dioxane.
2. A method for synthesizing 3- (3-butyn-1-yl) -3H-diazo-3-ethanol by using the (3-ethanol-3H-biaziridine) propiolactone, comprising the following steps:
(1) The (3-ethanol-3H-bisaziridine) propiolactone and diisobutyl aluminum hydride are mixed according to a molar ratio of 1:1 to 1.5 percent of the catalyst is added into a dichloromethane solvent to be fully reacted, and 3-acetaldehyde-3H-diazo-3-n-propionic acid is obtained after post treatment;
(2) 3-acetaldehyde-3H-diazo-3-n-propionic acid, and dimethyl (1-diazo-2-oxopropyl) phosphonate and potassium carbonate in a molar ratio of 1:1-1.5:2-2.5 percent of the total weight of the mixture is added into methanol to complete the reaction, and 3- (3-butyn-1-yl) -3H-diazo-3-ethanol is obtained after the post treatment.
3. A method for synthesizing 3-acetic acid-3H-diazo-3-n-propionic acid by using the (3-ethanol-3H-biaziridine) propionic acid lactone, comprising the following steps:
(1) Reacting (3-ethanol-3H-biaziridine) propiolactone, tetrahydrofuran and lithium hydroxide at constant temperature for 3 hours until the reaction is completed, and performing aftertreatment to obtain 3-ethanol-3H-diazo-3-n-propionic acid;
(2) Adding 3-acetic acid-3H-diazo-3-n-propionic acid and a dess martin oxidant into a reaction solvent, reacting at constant temperature overnight until the reaction is completed, and performing post-treatment to obtain the 3-acetic acid-3H-diazo-3-n-propionic acid.
4. A method for synthesizing 3- (2-haloethyl) -3H-diazo-3-n-propionic acid by using the (3-ethanol-3H-biaziridine) propionic acid lactone, comprising the following steps:
(1) Adding (3-ethanol-3H-bisaziridine) propiolactone and methanol hydrochloride solution into a closed reaction kettle, reacting at room temperature to 90 ℃ until the reaction is complete, and performing post-treatment to obtain 3-ethanol-3H-diazo-3-methyl n-propionate; on the premise of ensuring the reaction completion, the hydrochloric acid methanol solution does not emit hydrogen chloride gas to pollute the environment, and the consumption of the hydrochloric acid methanol solution is reduced as much as possible;
(2) Mixing 3-ethanol-3H-diazo-3-n-methyl propionate obtained in the step (1), halogenated compound and triphenylphosphine according to a molar ratio of 1:1 to 3: 1-3, and adding the mixture into a reaction solvent until the reaction is completed, and performing post-treatment to obtain 3- (2-halogenated ethyl) -3H-diazo-3-n-methyl propionate;
(3) Adding the 3- (2-haloethyl) -3H-diazo-3-n-propionic acid methyl ester obtained in the step (2) and alkali into a reaction solvent, and carrying out post-treatment until the reaction is complete to obtain 3- (2-haloethyl) -3H-diazo-3-n-propionic acid;
(4) 3-ethanol-3H-diazo-3-n-propionic acid and ethyl sulfonyl chloride are mixed according to a mole ratio of 1:1 to 1.5 percent of the catalyst is added into alkali and reaction solvent until the reaction is complete, and 3- (2-ethylsulfonyloxyethyl) -3H-diazo-3-normal propionic acid is obtained after post treatment.
Further, the halide in the step (2) is one of N-chlorosuccinimide, N-bromosuccinimide, carbon tetrachloride and carbon tetrabromide; the reaction solvent is one of tetrahydrofuran, dichloromethane, N-dimethylformamide, ethanol and methanol. Preferably, the reaction solvent is dichloromethane.
Further, the alkali in the step (3) is sodium hydroxide, lithium hydroxide, potassium hydroxide, sodium methoxide or potassium carbonate; the reaction solvent is at least one of methanol, ethanol, tetrahydrofuran and dioxane; the base in the step (4) is triethylamine, pyridine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, potassium carbonate, sodium carbonate or sodium hydroxide; the reaction solvent in the step (4) is dichloromethane, tetrahydrofuran, 1, 4-dioxane, toluene, ethyl acetate and pyridine.
5. A method for synthesizing 3-ethanol-3H-diazo-3-n-propionyl hydrazine by using the (3-ethanol-3H-bisaziridine) propiolactone, comprising the following steps: the (3-ethanol-3H-biaziridine) propiolactone and hydrazine are mixed according to a molar ratio of 1: 1-2, and the reaction temperature is between room temperature and 80 ℃ until the reaction is completed, and the 3-ethanol-3H-diazo-3-n-propionyl hydrazine is obtained after the reaction is completed, wherein the hydrazine is hydrazine hydrate or sulfonyl hydrazine, and the solvent is methanol, ethanol, tetrahydrofuran or dioxane.
6. A method for synthesizing 3-ethanol-3H-diazo-3-n-propionyl hydrazine by using the (3-ethanol-3H-bisaziridine) propiolactone, comprising the following steps: the (3-ethanol-3H-biaziridine) propiolactone and amine are mixed according to a molar ratio of 1: 1-2, and the reaction temperature is room temperature to 80 ℃, and the N-benzyl-3-ethanol-3H-diazo-3-N-propionamide is obtained after the reaction is completed, wherein the amine is benzylamine or alkylamine, and the reaction solvent is methanol, ethanol, tetrahydrofuran or dioxane.
Compared with the prior art, the invention has the advantages that: the invention discloses a method for synthesizing a photoaffinity probe reagent 3- (3-ethanol-3H-bisaziridine) propiolactone and application thereof, wherein 3, 3-cyclopentylidene- (3H-bisaziridine) -6-ketone is taken as a starting raw material, a key intermediate (3-ethanol-3H-bisaziridine) propiolactone is prepared in advance, the 3, 3-cyclopentylidene- (3H-bisaziridine) -6-ketone is cheap and easy to obtain, the use of dangerous reagents such as benzene, lithium aluminum hydride and the like is avoided, the process is safer and more reliable, and industrialization can be realized.
Meanwhile, important probe reagents such as 3-ethanol-3H-diazo-3-N-propionic acid, 3-ethanol-3H-diazo-3-N-propionic acid methyl ester, 3- (2-iodoethyl) -3H-diazo-3-N-propionic acid, 3- (2-bromoethyl) -3H-diazo-3-N-propionic acid, 3- (2-chloroethyl) -3H-diazo-3-N-propionic acid, 3-acetic acid-3H-diazo-3-N-propionic acid, 3-acetaldehyde-3H-diazo-3-N-propionic acid, 3-ethanol-3H-diazo-3-N-propionylhydrazine, N-benzyl-3-ethanol-3H-diazo-3-N-propionamide and the like are prepared by taking (3-ethanol-3H-diazepine propiolactone as a starting material. The probe reagent has a functional group at two ends of the bisaziridine, can be applied to coupling modification of DNA, RNA, protein and polypeptide, and can also be applied to preparation of photoaffinity covalent labeling probes of small molecule drugs and rigid covalent labeling application of forming a ring.
Drawings
FIG. 1 is a nuclear magnetic resonance spectrum of compound 1 in example 1;
FIG. 2 is a nuclear magnetic resonance spectrum of Compound 3 in example 2;
FIG. 3 is a nuclear magnetic resonance spectrum of Compound 4 in example 3;
FIG. 4 is a nuclear magnetic resonance spectrum of Compound 5 in example 3;
FIG. 5 is a nuclear magnetic resonance spectrum of compound 6 in example 4;
FIG. 6 is a nuclear magnetic resonance spectrum of compound 8A of example 4;
FIG. 7 is a nuclear magnetic resonance spectrum of compound 8B in example 4;
FIG. 8 is a nuclear magnetic resonance spectrum of compound 9 in example 5;
FIG. 9 is a nuclear magnetic resonance spectrum of compound 10 of example 6;
FIG. 10 is a nuclear magnetic resonance spectrum of compound 11 in example 7.
Detailed Description
The invention is described in further detail below with reference to the embodiments of the drawings.
The following detailed description of the embodiments and the advantages achieved by the embodiments is provided to assist the reader in better understanding the nature and characteristics of the invention and is not intended to limit the scope of what may be practiced. The structure of the compounds is determined by Nuclear Magnetic Resonance (NMR) and/or Mass Spectrometry (MS).
The NMR measurements were performed using a (Bruker ADVANCE III MHz) nuclear magnetic resonance apparatus with deuterated chloroform (CDCl 3), deuterated dimethyl sulfoxide (DMSO-d 6), internal standard Tetramethylsilane (TMS), and 1 H NMR information in the following format: chemical shifts (multiplets (s, singlet: d, doublet: t, triplet: q, quartet; m, multiplet), proton number). As a silica gel plate for MS measurement (Thermo Q Exactive Plus) thin layer chromatography, a tobacco stand yellow sea HSGF254 or Qingdao GF254 silica gel plate was used, and the silica gel plate used for Thin Layer Chromatography (TLC) was 0.20mm to 0.25mm in size. Column chromatography generally uses tobacco stage yellow sea silica gel 200-300 mesh silica gel as carrier. The known starting materials of the present invention may be synthesized or purchased from An Naiji chemical, michael chemical, bi De pharmaceutical, pharmaceutical Co., ltd, carbofuran technologies Co., sigma-Aldrich, etc., using methods known in the art.
Example 1
3, 3-Cyclopentamethylene- (3H-bisaziridine) -6-one (4.1 g,33.02mmol,1.0 eq.) was dissolved in 50mL of dried dichloromethane, m-CPBA (m-chloroperoxybenzoic acid) (8.05 g,39.63mmol,1.2 eq.) was added and the reaction was stirred at 50℃for 2H. The solid was filtered off, part of the dichloromethane was evaporated off in vacuo, 100mL of sodium thiosulfate solution was added and stirred at room temperature for 30min, extracted with dichloromethane, and purified by column chromatography (SiO 2, pure petroleum ether to 20% ethyl acetate/petroleum ether gradient elution) to give compound 1 (3.3 g, 71.3% yield) as a pale yellow solid. Nuclear magnetic resonance is shown in FIG. 1 at ,1H NMR(400MHz,Chloroform-d)δ4.52–4.39(m,2H),2.91–2.84(m,2H),1.70–1.55(m,2H),1.54–1.47(m,2H).MS(ESI):C6H8N2O2,Calcd.for[M+H]+:141.0659,found 141.1, to illustrate the successful synthesis of the target 3, 3-cyclopentylidene- (3H-bisaziridine) -6-one.
Example 2
1. Compound 1 (3.1 g,22.12mmol,1.0 eq.) prepared in example 1 was dissolved in 40mL of dry dichloromethane, the temperature was reduced to about 78℃and DIBAL-H (diisobutylaluminum hydride 1.5M in tolene) (about 18mL,1.2 eq.) was slowly added, and the reaction was continued at that temperature for 1H. After the reaction, the reaction mixture was quenched by dropwise addition to 100mL of a saturated sodium bicarbonate solution, and the system was in the form of a white colloid, and extracted 4 times with 200mL of ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and dried by spin to give crude compound 2 (about 3.01 g) as a pale yellow oil which was directly fed to the next step. MS (ESI): C 6H10N2O2,Calcd.for[M+Na]+: 165.1472,found 165.1.
2. The crude compound 2 (3.01 g, crude) was dissolved in 40mL of dry methanol, potassium carbonate (7.0 g,50.72mmol,2.3eq., calculated as compound 3) was added at room temperature with sufficient stirring, and (1-diazo-2-oxopropyl) phosphonate diester (5.1 g,26.54mmol,1.2eq., calculated as compound 3) was added and reacted at room temperature for 1h. 100mL of water was added to the reaction system for quenching, 150mL of ethyl acetate was used for extraction for 3 times, the organic phase was washed with saturated brine and dried over anhydrous sodium sulfate, and after sand making and column chromatography (SiO 2, pure petroleum ether to 15% ethyl acetate/petroleum ether gradient elution) the pale yellow oily compound 3 (1.9 g, yield 62.2%, calculated as compound 3) was obtained, and the nuclear magnetic resonance spectrum showed ,1H NMR(400MHz,DMSO-d6)δ4.52-4.49(m,1H),3.22–3.15(m,2H),2.74(q,J＝2.7Hz,1H),1.93-1.91(m,2H),1.54-1.50(m,2H),1.47-1.43(m,2H).MS(ESI):C7H10N2O,Calcd.for[M+H]+:139.1780,found 139.1. as shown in FIG. 2, to successfully synthesize the target substance 3- (3-butyn-1-yl) -3H-diazo-3-ethanol.
Example 3
1. Compound 1 (201.5 mg,1.42mmol,1.00 eq.) was added to a 8mL vial, tetrahydrofuran (2.00 mL) was added at room temperature to dissolve, lithium hydroxide (172.50 mg,7.13mmol,5.00 eq.) was added at room temperature (dissolved in 2mL water), the reaction was allowed to proceed at constant temperature for 3h, pH was adjusted to weak acidity, extracted 3 times with ethyl acetate, washed 2 times with saturated brine, and the ethyl acetate phase was dried over anhydrous sodium sulfate, filtered, and dried to give compound 4 as a colorless oil (189.0 mg,84% yield). The nuclear magnetic resonance spectrum is shown in figure 3 ,1H NMR(400MHz,DMSO-d6)δ3.28(d,J＝3.3Hz,2H),2.11-1.99(m,2H),1.74-1.60(m,2H),1.55–1.46(m,2H).MS(ESI):C6H10N2O3,Calcd.for[M-H]-:157.0619,found 157.1.
2. Compound 4 (50.2 mg,0.31mmol,1.00 eq.) is added to an 8mL vial, dess-Martin oxidant (535.7 mg,1.26mmol,4.00 eq.) is added at room temperature, dichloromethane (2.00 mL) is added, the reaction mixture is spun dry after overnight at constant temperature, directly purified by Flash reverse phase, and concentrated to dryness to afford compound 5 as a white solid, 3-ethanol-3H-diazo-3-n-propionic acid methyl ester/3- (2-haloethyl) -3H-diazo-3-n-propionic acid (15.0 mg,28% yield). The nuclear magnetic resonance spectrum is shown in FIG. 4 ,1H NMR(400MHz,DMSO-d6)δ2.32(s,2H),2.06(t,J＝7.5Hz,2H),1.70(t,J＝7.5Hz,2H).MS(ESI):C6H12N4O2,Calcd.for[M-H]-:171.0411,found 171.1.
Example 4
1. Compound 1 (240.0 mg,1.71mmol,1.0 eq.) was weighed into a 20mL pressure-resistant tube, and then reacted overnight at 90 degrees with the addition of 4M hydrogen chloride in methanol (5 mL), followed by LCMS monitoring the reaction (positive signal with signal peaks 173.1 and 195.1), and after concentrating the system, silica gel column purification (SiO 2, pure petroleum ether to 30% ethyl acetate/petroleum ether gradient elution) afforded compound 6 (240 mg, yield 81.4%) as a pale yellow oil. The nuclear magnetic resonance spectrum is shown in FIG. 5, MS (ESI) C 7H12N2O3,Calcd.for[M+H]+: 173.0921,found 173.1.
2. Compound 6 (500.0 mg,2.90mmol,1.00 eq.) triphenylphosphine (1523.0 mg,5.81mmol,2.00 eq.) and carbon tetrabromide (1926.0 mg,5.81mmol,2.00 eq.) were weighed into a 40mL reaction flask, 20mL dry DCM (added under ice bath) was added, reacted overnight at room temperature, monitored by TLC (PE/ea=10:1, rf=0.6). Quenched with water, extracted twice with EA, the organic phase dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography (SiO 2, gradient elution of pure petroleum ether to 5% ethyl acetate/petroleum ether) to afford compound 7A as a pale yellow oil (580 mg, yield) 85％).MS(ESI):C7H11BrN2O2,Calcd.for[M+Na]+:256.9896,258.9876,found 257.0,259.0.
3. Compound 7A (580.0 mg,2.47mmol,1.00 eq.) was dissolved in 2mL of methanol and 2mL of tetrahydrofuran, and then about 3mL of 1M sodium hydroxide solution was added dropwise, reacted at room temperature for 1h, and the reaction monitored by tlc (DCM/meoh=25:1, rf=0.4). Methanol and tetrahydrofuran were dried, the system was acidified with 20% HCl, extracted with EA, and the organic phase was dried over anhydrous sodium sulfate and concentrated. Sand was purified by column chromatography (SiO 2, gradient elution of pure dichloromethane to 5% methanol/dichloromethane) to give compound 8A as a pale yellow oil (500 mg, 92% yield). The nuclear magnetic resonance spectrum is shown in FIG. 6 ,1H NMR(400MHz,Chloroform-d)δ3.15(t,J＝7.0Hz,2H),2.18(t,J＝7.6Hz,2H),2.02(t,J＝7.0Hz,2H),1.84(t,J＝7.6Hz,2H).MS(ESI):C6H9BrN2O2,Calcd.for[M+Na]+:242.9740,244.9719,found 243.0,245.0.
4. Triphenylphosphine (1220.0 mg,4.65mmol,1.60 eq.) and iodine (1105.0 mg,4.36mmol,1.50 eq.) were added to a 100mL three-necked flask, argon was replaced, 20mL of dry DCM was added, a solution of imidazole (396.0 mg,5.81mmol,2.00 eq.) in dichloromethane was added under ice-salt bath, stirring was continued for 15min at this temperature, and a solution of compound 6 (500.0 mg,2.90mmol,1.00 eq.) in dichloromethane was added and reacted to room temperature overnight. TLC monitoring (PE/ea=10:1, rf=0.6). Quenched with sodium thiosulfate solution, extracted twice with EA, and the organic phase was dried over anhydrous sodium sulfate and concentrated. Sand-making and purifying by column (SiO 2, gradient elution of pure petroleum ether to 5% ethyl acetate/petroleum ether) to obtain pale yellow oily compound 7B (650 mg, yield) 79％).MS(ESI):C7H11IN2O2,Calcd.for[M+Na]+:304.9757,found 305.0.
5. Starting compound 7B (650.0 mg,2.30mmol,1.00 eq.) was dissolved in 2mL of methanol and 2mL of tetrahydrofuran, and about 3mL of 1M sodium hydroxide solution was added dropwise, reacted at room temperature for 1h, tlc monitored the reaction (DCM/meoh=25:1, rf=0.4). Methanol and tetrahydrofuran were dried, the system was acidified with 20% HCl, extracted with EA, and the organic phase was dried over anhydrous sodium sulfate and concentrated. Sand was purified by column chromatography (SiO 2, pure dichloromethane to 5% methanol/dichloromethane gradient elution) to afford compound 8B (560 mg, 91% yield) as a pale yellow solid. The nuclear magnetic resonance spectrum is shown in FIG. 7 ,1H NMR(400MHz,Chloroform-d)δ2.88(t,J＝7.5Hz,2H),2.17(t,J＝7.5Hz,2H),2.10(t,J＝7.5Hz,2H),1.83(t,J＝7.5Hz,2H).MS(ESI):C6H9IN2O2,Calcd.for[M+Na]+:290.9601,found 291.0.
Example 5
Compound 4 (49.70 mg,0.31mmol,1.00 eq.) was added to a 8mL vial, dissolved in dichloromethane (1.00 mL) at room temperature, and triethylamine (48.50 mg,0.47mmol,1.50eq., 99.5%) and ethylsulfonyl chloride (48.30 mg,0.37mmol,1.20eq., 98%) were added at room temperature and reacted overnight at constant temperature, purified directly by reverse phase, concentrated and lyophilized to give a nuclear magnetic resonance confirmation product to give colorless oil 9 (4.80 mg,6% yield). The nuclear magnetic resonance spectrum is shown in FIG. 8 ,LCMS-EI(m/z):[M+Na]+calculated for C8H14N2O5S 250.06,found 273.1.1HNMR(400MHz,DMSO-d6)δ4.05(t,J＝5.9Hz,2H),3.34(d,J＝7.3Hz,2H),2.06(s,2H),1.80(t,J＝6.0Hz,2H),1.68(d,J＝7.1Hz,2H),1.26(t,J＝7.3Hz,3H).
Example 6
Compound 1 (100 mg,0.7 mmol) was dissolved in 1mL of dry methanol, 50% hydrazine hydrate (68 mg,1.06mmol,1.4 eq.) was added at room temperature and stirred well at room temperature overnight. Direct concentration gave compound 10 (82.3 mg, 57.7% yield) as a colourless oil. The nuclear magnetic resonance spectrum is shown in FIG. 9 ,LCMS-EI(m/z):[M+H]+calculated for C6H12N4O2 173.1039,found 173.1.1H NMR(500MHz,DMSO-d6)δ8.96(s,1H),4.56(s,1H),3.24(t,J＝7.1Hz,2H),3.17(s,2H),1.83(t,J＝7.7Hz,2H),1.62(t,J＝7.9Hz,2H),1.47(t,J＝7.0Hz,2H).
Example 7
Compound 1 (100 mg,0.7 mmol) was dissolved in 1mL of dry THF, benzylamine (75 mg,0.77mmol,1.1 eq.) was added at room temperature and stirred well at room temperature overnight. Concentration gave compound 11 (127.3 mg, yield) as a pale yellow oil 75.5％).LCMS-EI(m/z):[M+H]+calculated for C13H17N3O2 248.1399,found
248.2. The nuclear magnetic resonance spectrum is shown in FIG. 10 ,1H NMR(400MHz,DMSO-d6)δ7.49(t,J＝6.0Hz,1H),6.49–6.31(m,5H),3.70(t,J＝4.7Hz,1H),3.37(d,J＝5.9Hz,2H),2.37(td,J＝6.4,3.6Hz,2H),1.08(dd,J＝8.8,6.7Hz,2H),0.79(dd,J＝8.8,6.8Hz,2H),0.60(t,J＝6.5Hz,2H).
The above description is not intended to limit the invention, nor is the invention limited to the examples described above. Variations, modifications, additions, or substitutions will occur to those skilled in the art and are therefore within the spirit and scope of the invention.
Claims (4)
1. A method for synthesizing 3- (3-ethanol-3H-biaziridine) propiolactone, which is characterized by comprising the following steps: 3, 3-cyclopentylidene- (3H-bisaziridine) -6-one and m-chloroperoxybenzoic acid are mixed according to a molar ratio of 1: 1-1.5, and at the reaction temperature of room temperature to 50 ℃, obtaining 3- (3-ethanol-3H-biaziridine) propiolactone after the reaction is completed, wherein the specific structure of the 3- (3-ethanol-3H-biaziridine) propiolactone is as follows:
Wherein the specific structure of the starting 3, 3-cyclopentylidene- (3H-bisaziridine) -6-one is shown as follows:
2. The method for synthesizing 3- (3-ethanol-3H-biaziridine) propiolactone as claimed in claim 1, wherein: the molar ratio of the 3, 3-cyclopentylene- (3H-bisaziridine) -6-ketone to the m-chloroperoxybenzoic acid is 1:1.2.
3. The method for synthesizing 3- (3-ethanol-3H-biaziridine) propiolactone as claimed in claim 1, wherein: the reaction solvent is at least one of dichloromethane, N-dimethylformamide and 1, 4-dioxane.
4. A method for synthesizing 3- (3-butyn-1-yl) -3H-diazo-3-ethanol using the 3- (3-ethanol-3H-bisaziridine) propanoic acid lactone of claim 1, comprising the steps of:
(1) 3- (3-ethanol-3H-bisaziridine) propiolactone and diisobutyl aluminum hydride are mixed according to a molar ratio of 1:1 to 1.5 percent of the catalyst is added into a dichloromethane solvent to be fully reacted, and 3-acetaldehyde-3H-diazo-3-n-propanol is obtained after post treatment;
(2) 3-acetaldehyde-3H-diazo-3-n-propanol, and dimethyl (1-diazo-2-oxopropyl) phosphonate and potassium carbonate in a molar ratio of 1:1-1.5:2-2.5 percent of the total weight of the catalyst is added into methanol until the reaction is complete, and 3- (3-butyn-1-yl) -3H-diazo-3-ethanol is obtained after the post treatment.
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