CN114057690A - Clathrate compound of semi-cucurbit [6] uril and tobacco alkaloid, preparation method and application thereof - Google Patents
Clathrate compound of semi-cucurbit [6] uril and tobacco alkaloid, preparation method and application thereof Download PDFInfo
- Publication number
- CN114057690A CN114057690A CN202111446642.0A CN202111446642A CN114057690A CN 114057690 A CN114057690 A CN 114057690A CN 202111446642 A CN202111446642 A CN 202111446642A CN 114057690 A CN114057690 A CN 114057690A
- Authority
- CN
- China
- Prior art keywords
- semi
- cucurbit
- urea
- nicotine
- tobacco
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 53
- 241000208125 Nicotiana Species 0.000 title claims abstract description 51
- 235000002637 Nicotiana tabacum Nutrition 0.000 title claims abstract description 51
- 229930013930 alkaloid Natural products 0.000 title claims abstract description 44
- 150000003797 alkaloid derivatives Chemical class 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title abstract description 11
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 132
- 239000004202 carbamide Substances 0.000 claims abstract description 130
- 239000000126 substance Substances 0.000 claims abstract description 17
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 85
- 229960002715 nicotine Drugs 0.000 claims description 85
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 84
- 238000003756 stirring Methods 0.000 claims description 33
- MYKUKUCHPMASKF-VIFPVBQESA-N (S)-nornicotine Chemical compound C1CCN[C@@H]1C1=CC=CN=C1 MYKUKUCHPMASKF-VIFPVBQESA-N 0.000 claims description 23
- MYKUKUCHPMASKF-UHFFFAOYSA-N Nornicotine Natural products C1CCNC1C1=CC=CN=C1 MYKUKUCHPMASKF-UHFFFAOYSA-N 0.000 claims description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- VEKIYFGCEAJDDT-UHFFFAOYSA-N 2-pyridin-3-ylpyridine Chemical compound N1=CC=CC=C1C1=CC=CN=C1 VEKIYFGCEAJDDT-UHFFFAOYSA-N 0.000 claims description 13
- 238000001035 drying Methods 0.000 claims description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- 239000012141 concentrate Substances 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 10
- 238000004108 freeze drying Methods 0.000 claims description 7
- 238000001694 spray drying Methods 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 5
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 5
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 235000019253 formic acid Nutrition 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- SOPPBXUYQGUQHE-JTQLQIEISA-N Anatabine Chemical compound C1C=CCN[C@@H]1C1=CC=CN=C1 SOPPBXUYQGUQHE-JTQLQIEISA-N 0.000 claims description 3
- SOPPBXUYQGUQHE-UHFFFAOYSA-N Anatabine Natural products C1C=CCNC1C1=CC=CN=C1 SOPPBXUYQGUQHE-UHFFFAOYSA-N 0.000 claims description 3
- 235000013305 food Nutrition 0.000 claims description 3
- 238000010025 steaming Methods 0.000 claims description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 2
- 239000002537 cosmetic Substances 0.000 claims description 2
- 239000000796 flavoring agent Substances 0.000 claims description 2
- 235000019634 flavors Nutrition 0.000 claims description 2
- 239000003205 fragrance Substances 0.000 claims description 2
- ATWWUVUOWMJMTM-UHFFFAOYSA-N N-Methylanatabine Natural products CN1CC=CCC1C1=CC=CN=C1 ATWWUVUOWMJMTM-UHFFFAOYSA-N 0.000 claims 1
- 239000000654 additive Substances 0.000 claims 1
- 230000000996 additive effect Effects 0.000 claims 1
- DPNGWXJMIILTBS-UHFFFAOYSA-N dehydronornicotine Natural products C1CCN=C1C1=CC=CN=C1 DPNGWXJMIILTBS-UHFFFAOYSA-N 0.000 claims 1
- 239000002417 nutraceutical Substances 0.000 claims 1
- 235000021436 nutraceutical agent Nutrition 0.000 claims 1
- 238000007789 sealing Methods 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract description 5
- 230000002209 hydrophobic effect Effects 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 3
- 230000003993 interaction Effects 0.000 abstract description 2
- 230000001105 regulatory effect Effects 0.000 abstract description 2
- 235000013877 carbamide Nutrition 0.000 description 120
- 235000009852 Cucurbita pepo Nutrition 0.000 description 17
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- 241000219122 Cucurbita Species 0.000 description 11
- 238000010521 absorption reaction Methods 0.000 description 11
- 238000002156 mixing Methods 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 9
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 9
- 240000001980 Cucurbita pepo Species 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 239000006069 physical mixture Substances 0.000 description 8
- 238000001228 spectrum Methods 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
- 230000014759 maintenance of location Effects 0.000 description 7
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- 238000002441 X-ray diffraction Methods 0.000 description 6
- MSBXTPRURXJCPF-DQWIULQBSA-N cucurbit[6]uril Chemical compound N1([C@@H]2[C@@H]3N(C1=O)CN1[C@@H]4[C@@H]5N(C1=O)CN1[C@@H]6[C@@H]7N(C1=O)CN1[C@@H]8[C@@H]9N(C1=O)CN([C@H]1N(C%10=O)CN9C(=O)N8CN7C(=O)N6CN5C(=O)N4CN3C(=O)N2C2)C3=O)CN4C(=O)N5[C@@H]6[C@H]4N2C(=O)N6CN%10[C@H]1N3C5 MSBXTPRURXJCPF-DQWIULQBSA-N 0.000 description 6
- 238000001157 Fourier transform infrared spectrum Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 238000002390 rotary evaporation Methods 0.000 description 5
- 150000001993 dienes Chemical class 0.000 description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- SWWQQSDRUYSMAR-UHFFFAOYSA-N 1-[(4-hydroxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinoline-6,7-diol;hydrochloride Chemical group Cl.C1=CC(O)=CC=C1CC1C2=CC(O)=C(O)C=C2CCN1 SWWQQSDRUYSMAR-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000003337 fertilizer Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 150000003672 ureas Chemical class 0.000 description 3
- ONIKNECPXCLUHT-UHFFFAOYSA-N 2-chlorobenzoyl chloride Chemical group ClC(=O)C1=CC=CC=C1Cl ONIKNECPXCLUHT-UHFFFAOYSA-N 0.000 description 2
- FBCWFOLOHWOWFX-UHFFFAOYSA-N 2-methoxy-2-methylpropane;hydrate Chemical compound O.COC(C)(C)C FBCWFOLOHWOWFX-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 229920001807 Urea-formaldehyde Polymers 0.000 description 2
- 238000005452 bending Methods 0.000 description 2
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- 238000006243 chemical reaction Methods 0.000 description 2
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- 201000010099 disease Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 2
- HQVFCQRVQFYGRJ-UHFFFAOYSA-N formic acid;hydrate Chemical compound O.OC=O HQVFCQRVQFYGRJ-UHFFFAOYSA-N 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
- WHQSYGRFZMUQGQ-UHFFFAOYSA-N n,n-dimethylformamide;hydrate Chemical compound O.CN(C)C=O WHQSYGRFZMUQGQ-UHFFFAOYSA-N 0.000 description 2
- OWBDZKIEYJOQMV-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine;hydrate Chemical compound O.CCN(C(C)C)C(C)C OWBDZKIEYJOQMV-UHFFFAOYSA-N 0.000 description 2
- -1 nitrogen-containing heterocyclic compound Chemical class 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
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- YHBIGBYIUMCLJS-UHFFFAOYSA-N 5-fluoro-1,3-benzothiazol-2-amine Chemical compound FC1=CC=C2SC(N)=NC2=C1 YHBIGBYIUMCLJS-UHFFFAOYSA-N 0.000 description 1
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- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 240000009087 Crescentia cujete Species 0.000 description 1
- 235000005983 Crescentia cujete Nutrition 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
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- MGPYDQFQAJEDIG-UHFFFAOYSA-N ethene;urea Chemical group C=C.NC(N)=O MGPYDQFQAJEDIG-UHFFFAOYSA-N 0.000 description 1
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- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 1
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- 230000004060 metabolic process Effects 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
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- 208000009954 pyoderma gangrenosum Diseases 0.000 description 1
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Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
- A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
- A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
- A24B15/18—Treatment of tobacco products or tobacco substitutes
- A24B15/28—Treatment of tobacco products or tobacco substitutes by chemical substances
- A24B15/281—Treatment of tobacco products or tobacco substitutes by chemical substances the action of the chemical substances being delayed
- A24B15/283—Treatment of tobacco products or tobacco substitutes by chemical substances the action of the chemical substances being delayed by encapsulation of the chemical substances
-
- A—HUMAN NECESSITIES
- A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
- A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
- A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
- A24B15/18—Treatment of tobacco products or tobacco substitutes
- A24B15/28—Treatment of tobacco products or tobacco substitutes by chemical substances
- A24B15/30—Treatment of tobacco products or tobacco substitutes by chemical substances by organic substances
- A24B15/36—Treatment of tobacco products or tobacco substitutes by chemical substances by organic substances containing a heterocyclic ring
- A24B15/38—Treatment of tobacco products or tobacco substitutes by chemical substances by organic substances containing a heterocyclic ring having only nitrogen as hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D213/22—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing two or more pyridine rings directly linked together, e.g. bipyridyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
- C11B9/00—Essential oils; Perfumes
- C11B9/0069—Heterocyclic compounds
- C11B9/0092—Heterocyclic compounds containing only N as heteroatom
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Toxicology (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Wood Science & Technology (AREA)
- Botany (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicinal Preparation (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a clathrate compound of semi-cucurbit [6] urea and tobacco alkaloid, which contains tobacco alkaloid and semi-cucurbit [6] urea, wherein the molar ratio of the tobacco alkaloid to the semi-cucurbit [6] urea is 1-10: 1, and the semi-cucurbit [6] urea molecule is provided with a hydrophobic cavity, so that the semi-cucurbit [6] urea molecule and the tobacco alkaloid form good cavity matching; meanwhile, electronegativity of the carbonyl of the semi-cucurbit [6] urea molecule has interaction with the tobacco alkaloid, so that the stability and the release of the tobacco alkaloid can be regulated and controlled while the binding property of the host and the guest substances is enhanced; the preparation method of the inclusion compound is simple, convenient and feasible, has mild conditions and is suitable for industrial production.
Description
Technical Field
The invention relates to the technical field of flavors and fragrances, tobacco, cosmetics, food and medicines, in particular to a novel system of tobacco alkaloid and a preparation method and application thereof.
Background
The tobacco alkaloid, namely the basic nitrogen-containing heterocyclic compound in the tobacco, is a group of nicotine-like series, comprises more than 50 substances, is present in more than 60 different kinds of tobacco, and partial ingredients are also present in plants except the tobacco. Their individual components are also present in certain plants other than tobacco. The tobacco alkaloids mainly have two types according to the molecular structure, one type is a compound combining pyridine and hydrogenated pyrrole, such as nicotine (nicotine), demethyl nicotine (nornicotine), demethyl dehydronicotine (mesmin), diene nicotine (niceritrine), demethyl diene nicotine (norniceritrine) and the like; another class are compounds in which pyridine is combined with pyridine or hydrogenated pyridines, such as neonicotinoids (anapenem), N-methylneonicotinoids (N-methylantestin), dehydroneonicotinoids (anacetamide), N-methyldehydroneonicotinoids (N-methylantetamine), 2, 3-bipyridine, and the like.
Wherein Nicotine (Nicotine, chemical name is 1-methyl-2- (3' -pyridine) pyrrolidine) accounts for more than 95% of total alkaloids in tobacco. Nicotine has an excitatory or inhibitory effect on the central nervous system of the human body. Proper smoking can enhance the memory of people, and a small amount of nicotine can stimulate the central nervous system of the human body, so that the people can calm the spirit and relieve the tension of the people. Effective drugs for treating Alzheimer's disease, schizophrenia, Parkinson's disease, antioxidation, pyoderma gangrenosum and other diseases related to mental system disorders. Is a natural raw material for manufacturing medicaments which participate in human metabolism, improve peripheral nerve functions, dilate blood vessels and treat cardiovascular diseases. The high-purity nicotine can also be used as raw material for health cigarette, smoking stopping ointment, weight reducing medicine, and topical medicine for treating arthralgia and muscle spasm. The nicotine sulfate solution can prevent and control crop pests such as aphides, thrips, psyllids and the like in field crop production, is a high-efficiency, low-toxicity and broad-spectrum 'green' pesticide, has no residual toxicity, cannot cause secondary pollution, also meets the requirement of green food production, and is a bioactive pesticide for protecting the ecological environment. The compound of the compound fertilizer with the fertilizer can increase the fertilizer efficiency. In the prevention and treatment of diseases in animals, nicotine in the form of an aerosol can be used for disinfection of poultry houses. In the chemical industry, nicotine is also an important chemical raw material. Nicotinic acid and its derivatives can be prepared by oxidation and alcoholization.
Semi-cucurbit [6] ureas (semi-CB [6 ]) are a new member of the cucurbituril family. The structure can be regarded as half of the cutting along the chamber diameter of the cucurbit [6] uril (CB [6 ]). In the crystal structure of semi-cucurbit [6] urea, six ethylene urea units adopt an "alternating" conformation. They have a more flexible structure and are easier to synthesize than cucurbiturils. It possesses a hydrophobic cavity and two identical carbonyl inlets, and can be formed into stable inclusion compound with various molecules and ions. Compared with the flexible ring-opening cucurbituril, the closed-loop semi-cucurbituril [6] is also a flexible ring, and the preparation method is simple, convenient and feasible, has mild conditions and is suitable for industrial production. However, the solubility of semicarbazide in water is poor, which makes it difficult to study the host-guest reaction and inclusion of semicarbazide in solution. However, in the solvent of one or two of water, methanol, acetone, ether, tert-butyl methyl ether, triethanolamine, formic acid, DMF and DMSO, the solubility of the semi-CB 6 is greatly improved.
Regarding the patent of slow release of tobacco alkaloid, the publication number is CN107496364A a nicotine slow release microsphere and the preparation method publication number is CN104013603A a nicotine slow release patch. The publication number is CN106913559A a functional self-assembly polypeptide hydrogel nicotine sustained-release patch. No. CN104824850A discloses a smokeless cigarette without heat containing nicotine-containing sustained-release pellets. An inclusion compound of open-loop cucurbituril with an anion with a publication number of CN111303995A and nicotine substances, and a preparation method and application thereof. The tobacco alkaloid inclusion compounds reported in the patents are all prepared by increasing the slow release of tobacco alkaloid by using a method of using particles, micro-gel, gel and C-type semi-ring-opening cucurbituril, and forming the inclusion compound of the semi-cucurbituril [6] urea and the tobacco alkaloid by using a class of flexible cyclic molecule semi-cucurbituril [6] urea to carry out inclusion reaction with the tobacco alkaloid, which is not reported.
Disclosure of Invention
The invention provides a tobacco alkaloid inclusion compound with good stability and high binding constant, which contains tobacco alkaloid and half cucurbit [6] urea, wherein the molar ratio of the tobacco alkaloid to the half cucurbit [6] urea is 1-10: 1; the clathrate compound prepared by the invention has good water solubility, high stability, simple preparation method, mild condition and easy operation, can realize the release of the tobacco alkaloid in the clathrate compound by controlling the temperature, can be used for the development of the tobacco alkaloid, and has potential practical application value.
The structural formula of the semi-cucurbit [6] urea is as follows:
wherein R is selected from H, C2H5、OH、C6H12、OC3H5、OCOC2H5。
The half gourd [6]]The preparation of urea is carried out according to the known literature (Miyahara, Yuji, et al, "Remarkably facial ring-size control in macrocatalysis: Synthesis of semicucurbits [6]] uril and hemicucurbit [12]"Angewandte Chemie International Edition 43.38 (2004): 5019-]The synthesis reaction formula of urea is shown as follows, and the product is semi-cucurbita [6]]Nuclear magnetic resonance hydrogen spectrum of urea (R is H) (R) C1H NMR) is shown in FIG. 1.
For example, when R = H, the specific process is: dissolving ethylene urea and formaldehyde solution with equal molar ratio in 4mol/L hydrochloric acid solution, and reacting at room temperature for half an hour to obtain the product.
The structural formula of the tobacco alkaloid is as follows:
the preparation method of the clathrate compound of the semi-cucurbit [6] urea and the tobacco alkaloid comprises the steps of dissolving the semi-cucurbit [6] urea in a solvent (the solvent is one or two of water, methanol, acetone, ethyl ether, tert-butyl methyl ether, triethanolamine, N-diisopropylethylamine, formic acid, DMF and DMSO), adding the tobacco alkaloid into the semi-cucurbit [6] urea solution according to the molar ratio of the tobacco alkaloid to the semi-cucurbit [6] urea of 1: 1-10: 1, stirring for 6-168 hours at the temperature of 20-60 ℃, filtering to remove insoluble substances, carrying out reduced pressure concentration at the temperature of 40-60 ℃, and drying the clathrate compound of the concentrate (the drying method is one of rotary evaporation drying at the temperature of 40-60 ℃, freeze drying at the temperature of-10-50 ℃ and spray drying at the temperature of 50-80 ℃) to obtain the tobacco alkaloid.
Compared with the prior art, the method has the advantages and technical effects that:
the invention utilizes the semi-cucurbit [6] urea molecule with a hydrophobic cavity, thereby forming a good cavity matching with the tobacco alkaloid; meanwhile, electronegativity of the carbonyl of the semi-cucurbit [6] urea molecule has interaction with tobacco alkaloid, so that the stability and the release of the tobacco alkaloid can be regulated and controlled while the binding property of the two substances, namely a host and an object, is enhanced; the inclusion compound has good thermal stability, can be released at higher temperature, has simple and easy preparation method and mild conditions, and is suitable for industrial production; the inclusion compound prepared by the invention has good stability and high safety, and can effectively overcome the instability and easy volatility of the tobacco alkaloid and the analogues thereof in the production process.
Drawings
FIG. 1 shows a half gourd [6]]Nuclear magnetic resonance hydrogen spectrum of urea (R is H) (R) C1H NMR) pattern;
FIG. 2 shows nicotine and cucurbita pepo [6] in example 1]Nuclear magnetic resonance hydrogen spectrum of urea (R is H) clathrate (1H NMR) comparisonIn which A is a half gourd [6]]Urea (R is H); b is nicotine and semi-calabash [6]]Inclusion compounds of urea (R is H); c is nicotine;
FIG. 3 is a TG curve of the clathrate of nicotine and cucurbit [6] urea (R is H) in example 1; wherein 1 is semi cucurbit [6] uril (R is-H); 2 is a clathrate of nicotine and semi-cucurbit [6] urea (R is-H); 3 is a physical mixture of nicotine and semi-cucurbit [6] urea (R is-H); 4 is nicotine;
FIG. 4 is a comparison of the X-ray diffraction (XRD) pattern of the clathrate of nicotine and cucurbita [6] urea (R is H) in example 1, wherein a is cucurbita [6] urea (R is H); b is a physical mixture of nicotine and semi-cucurbit [6] urea (R is H); c is a clathrate compound of nicotine and semi-cucurbit [6] urea (R is H);
FIG. 5 is a graph of a Fourier transform infrared (FT-IR) spectrum of the clathrate of nicotine and semi-cucurbit [6] urea (R is H) in example 1, wherein a is semi-cucurbit [6] urea; b is nicotine; c is a physical mixture of nicotine and semi-cucurbit [6] urea (R is H); d is an inclusion compound of nicotine and semi-cucurbit [6] uril (R is H);
FIG. 6 is the heat release curves of the clathrate of nicotine and semi-cucurbit [6] urea (R is H) in example 1 at different temperatures;
FIG. 7 shows nornicotine and cucurbita pepo [6] in example 2]Nuclear magnetic resonance hydrogen spectrum of urea (R is H) clathrate (1H NMR) comparison chart, in which A is a half cucurbit [6]]Urea (R is H); b is nornicotine and semi-calabash [6]]Inclusion compounds of urea (R is H); c is nornicotine;
FIG. 8 is a graph of a Fourier transform infrared spectroscopy (FT-IR) comparison of the inclusion compound of nornicotine and semi-cucurbit [6] urea (R is H) in example 2, wherein a is semi-cucurbit [6] urea; b is nornicotine; c is a physical mixture of nornicotine and semi-cucurbit [6] urea (R is H); d is an inclusion compound of nornicotine and semi-cucurbit [6] urea (R is H);
FIG. 9 is the heat release curves of the clathrate of nornicotine and semi-cucurbit [6] urea (R is H) in example 2 at different temperatures.
Detailed Description
The method of the present invention is further described below by way of examples, but the scope of the present invention is not limited by the examples, and the reagents used in the examples are all conventional commercially available reagents or reagents prepared by conventional methods without specific descriptions, and the methods used are all conventional methods without specific descriptions.
Stirring for 6 h-7 days at 20-60 ℃, filtering, removing insoluble substances, concentrating under reduced pressure at 40-60 ℃ (the reduced pressure concentration method is one of rotary evaporation drying, freeze drying and spray drying), concentrating filtrate, and drying (the drying method is one of rotary evaporation drying at 40-60 ℃, freeze drying at-10-50 ℃ and spray drying at 50-80 ℃), thus obtaining the tobacco alkaloid clathrate compound.
Example 1: mixing 1mmol of semi-calabash [6]]Dissolving urea (R is H) in 25mL distilled water, stirring at 20 deg.C to dissolve, adding 2mmol nicotine to semi-cucurbit [6]]Stirring in urea solution at 30 deg.C for 12 hr, filtering, removing insoluble substances, concentrating at 50 deg.C under reduced pressure to remove water, and rotary evaporating the concentrate at 40 deg.C to dryness to obtain semi-cucurbit [6]]Inclusion compound of urea and nicotine with a yield of 96%; product nicotine and semi-calabash [6]]Nuclear magnetic resonance hydrogen spectrum of urea (R is H) clathrate (1H NMR) is shown in FIG. 2; by measuring in FIG. 21Changes in H NMR spectra to assess whether nicotine is contained in the cucurbita pepo [6]In the cavity of urea, nicotine and semi-cucurbit [6]]Before or after urea forms inclusion compound1H NMR chemical shifts are listed in Table 1, nicotine/semi-cucurbita [6]]Compared with free nicotine, the urea inclusion compound is prepared from cucurbita pepo [6]]The shielding effect of the urea cavity, the H-1,5 protons of nicotine in the clathrate all experienced a 0.07ppm field shift, the H-7 ', 8 protons all experienced a 0.28ppm field shift, the H-3 protons moved up 0.31ppm, the H-2 protons moved up 0.14ppm, the H-9' protons moved up 0.56 ppm, the H-6 protons moved up 0.41ppm, the H-9 protons moved up 0.36 ppm, the H-7 protons moved up 0.14ppm, and the H-10 protons moved up 0.23 ppm. In addition, when the inclusion compound is formed, the half cucurbits [6]]The chemical shifts of all proton peaks of urea (H-a, b) are hardly changed; these changes support nicotine and cucurbita pepo [6]]Formation of urea inclusion compound;
TABLE 1 Nicotine and hemi-CB [6]]Before and after the formation of inclusion compound1H NMR chemical shifts
The TG curve of the clathrate of nicotine and semi-cucurbit [6] urea (R is H) is shown in FIG. 3, the thermogravimetry of curve 4 shows that nicotine is completely degraded at 230 ℃, which shows that it is highly volatile, while the clathrate of nicotine and semi-cucurbit [6] urea (curve 2) is different from the thermogravimetry of semi-cucurbit [6] urea (curve 3) and the physical mixture of nicotine and semi-cucurbit [6] urea (R is-H), and the changes support the formation of the clathrate of nicotine and semi-cucurbit [6] urea;
XRD of clathrate of nicotine and semi-cucurbit [6] uril (R is H) is shown in figure 4, XRD pattern (a) of semi-cucurbit [6] uril is amorphous peak; and the XRD pattern (b) of the nicotine shows a series of sharp diffraction peaks at 4-30 degrees of 2 theta, which shows that the nicotine has better crystal form. In the XRD pattern (b) of the physical mixture of the semicarbazide and the nicotine, a characteristic peak of the semicarbazide [6] and a sharp diffraction peak of partial nicotine can be seen, which indicates that the semicarbazide and the nicotine are mixed together only in a physical mixing way. And the characteristic peak of CBD in the XRD pattern (c) of the clathrate compound of the semi-cucurbit [6] urea and the nicotine is completely disappeared, and the change supports the formation of the clathrate compound of the nicotine and the semi-cucurbit [6] urea.
Nicotine and semi-calabash [6]]FT-IR of urea (R is H) clathrate is shown in FIG. 5, and semi-cucurbita [6] in FIG. 5a]Urea at 2949.17cm-1And 2890.50cm-1Two C-H stretching vibration peaks of methylene are 1439.01cm-1And 1487.26cm-1Two C-H in-plane bending vibration peaks of methylene and 1696.35cm-1A more obvious carbonyl absorption peak is formed; the FT-IR spectral absorption bands of nicotine in FIG. 5b appear at 3410 cm each-1(C-H stretching vibration), 2981 cm-1、2950 cm-1、2779 cm-1(C-H stretching vibration), 1622 cm-1(C = C stretching vibration), 1256 cm-1(C-C stretching vibration); the FT-IR spectrum of the physical mixture in FIG. 5c shows the correlation with the half cucurbit [6]]Approximate superposition of the two spectra for urea and nicotine. However, nicotine/semi-cucurbita [6] in FIG. 5d]FT-IR spectrum of urea clathrate hardly showed the same as that of half gourd [6]]Urea has similar characteristics. Nicotine is located at 1021 cm−1 - 1215 cm−1At distance of 1334 cm−1 - 1473cm-1OfThe absorption band completely disappeared. This is due to the almost complete intense and broad spectrum of the two bands of nicotine [6]The urea band is masked. However, half gourd [6]]2890 cm of urea-1Has an absorption band of 2891cm-1And 2949 cm-1 and 1696 cm-12945cm of the absorption band direction-1And 1691 cm-1High frequency shift of (2). These changes may be due to nicotine and the semi-cucurbit [6]]The formation of intramolecular hydrogen bonds between ureas.
In order to examine the release performance of the nicotine inclusion compound at different temperatures, three equal parts of solid samples of the nicotine inclusion compound are respectively placed in constant temperature environments of 25 ℃, 60 ℃ and 120 ℃ for 3 days in an open heating mode, and 15 mg of samples are taken at specific time points (0, 2, 4, 8, 12, 24, 36, 48 and 72 h) to analyze the content of the guest in the inclusion compound. By using1H NMR to assess the nicotine content of the samples. The retention rate of nicotine in the clathrate was calculated by formula 1-1.
Retention (%) = Wt/W0X 100% (1-1)
In the formula, WtIs the nicotine content in the inclusion at time t, and W0 is the nicotine content in the inclusion at t = 0.
The heat release performance of the nicotine and semi-cucurbit [6] uril (R is H) inclusion compound is shown in figure 6, and the retention rate of nicotine is still kept above 70% after 72 hours at 120 ℃; this provides a feasible scheme for overcoming the defects of low-temperature volatilization and short retention time of nicotine.
Example 2: mixing 1mmol of semi-calabash [6]]Dissolving urea (R is H) in 25mL methanol, stirring at 20 deg.C to dissolve, adding 1.5mmol of nornicotine into semi-cucurbit [6]]Stirring in urea solution at 20 deg.C for 6 days, filtering to remove insoluble substances, concentrating at 60 deg.C under reduced pressure to remove methanol, and rotary steaming and drying the concentrate at 60 deg.C to obtain semi-cucurbit [6]]Inclusion compounds of urea with nornicotine in a yield of 90%. The product nornicotine and semi-calabash [6]]Nuclear magnetic resonance hydrogen spectrum of urea (R is H) clathrate (1H NMR) is shown in FIG. 7 by measuring the results shown in FIG. 71Changes in H NMR spectra to assess whether nicotine is contained in the cucurbita pepo [6]In the cavity of the urea. Nicotine and semi-calabash [6]]Before or after urea forms inclusion compound1H NMRThe chemical shifts are listed in table 2; nicotine/semi-cucurbit [6]]Compared with free nicotine, the urea inclusion compound is prepared from cucurbita pepo [6]]The shielding effect of the urea cavity, the H-1,5 protons of nicotine in the clathrate all experienced a 0.34 ppm field shift, the H-7 ', 8 protons all experienced a 0.28ppm field shift, the H-3 protons moved up 0.33 ppm, the H-2 protons moved up 0.16 ppm, the H-6 protons moved up 0.62 ppm, the H-9 protons moved up 0.60 ppm, the H-9 ' protons moved up 0.53 ppm, the H-10 protons moved up 0.35 ppm, the H-7 protons moved up 0.18 ppm, the H-8 ' protons moved up 0.38 ppm. In addition, when the inclusion compound is formed, the half cucurbits [6]]The chemical shifts of all proton peaks of urea (H-a, b) are hardly changed. These changes support nicotine and cucurbita pepo [6]]Formation of urea inclusion compound.
TABLE 2 nornicotine and hemi-CB [6]]Before and after the formation of inclusion compound1H NMR chemical shifts
Nicotine-reducing and half-gourd [6]]FT-IR of urea (R is H) clathrate is shown in FIG. 8, and semi-cucurbita [6] in FIG. 8a]Urea at 2949.17cm-1And 2890.50cm-1Two C-H stretching vibration peaks of methylene are 1439.01cm-1And 1487.26cm-1Two C-H in-plane bending vibration peaks of methylene and 1696.35cm-1Two carbonyl absorption peaks are obvious. The absorption bands of FT-IR spectrum of nornicotine in FIG. 8a appear at 2960 cm-1、2870 cm-1(C-H stretching vibration), 1675 cm-1、1580 cm-1(C = C telescopic vibration), and 1256 cm-1The absorption band at (C-C stretching vibration) can be attributed to aromatics. In the figure, the FT-IR spectrum of the physical mixture of c shows the half cucurbit [6]]Approximate superposition of the respective patterns of urea and nornicotine. However, FIG. 8d Nornicotin/semi-cucurbit [6]]FT-IR spectrum of urea clathrate hardly showed the same as that of half gourd [6]]Urea has similar characteristics. The nornicotine is located at 1030 cm−1 - 1421 cm−1The absorption band at (a) disappears completely. This is due to the almost completely intense and broad band of the two bands of nornicotine [6]The urea band is masked. However, 1649 cm of nornicotine-1At low frequency of absorption bandThe length is shifted to 1653 cm-1And half gourd [6]]2949 cm of urea-1The absorption band of the probe is shifted to 2945cm to a high frequency length-1. These changes may be due to nicotine and the semi-cucurbit [6]]The formation of intramolecular hydrogen bonds between ureas.
In order to examine the release performance of the nicotine reducing clathrate at different temperatures. Respectively taking three equal parts of solid samples of the nicotine-reducing inclusion compound, respectively placing the three equal parts of solid samples in constant temperature environments of 25 ℃, 60 ℃ and 120 ℃ for open heating for 3 days, taking out 15 mg of samples at specific time points (0, 2, 4, 8, 12, 24, 36, 48 and 72 h) to analyze the content of the object in the inclusion compound, and adopting the method1H NMR was used to estimate the nicotine content in the sample, and the retention of nicotine in the clathrate was calculated by the formula 1-1 in example 1.
The heat release performance of the clathrate of nornicotine and semi-cucurbit [6] uril (R is H) is shown in figure 9, and the retention rate of nornicotine is maintained above 70% after 72H at 120 ℃. The method provides a feasible scheme for overcoming the defects of low-temperature volatilization and short retention time of the nicotine.
Example 3: mixing 4mmol of semi-calabash [6]]Urea (R is C)6H12) Dissolving in 25mL DMF, stirring at 20 deg.C to dissolve, adding 7mmol of diene nicotine into semi-cucurbita [6]]Stirring in urea solution at 25 deg.C for 23 hr, concentrating under reduced pressure at 40 deg.C to remove DMF, and freeze drying at-20 deg.C to obtain semi-cucurbit [6]]Inclusion compound of urea with diennicotin, yield 97%.
Example 4: dissolving 2mmol of semi-cucurbit [6] urea (R is OH) in 25mL of DMSO, stirring at 20 ℃ until the semi-cucurbit [6] urea is dissolved, adding 10mmol of equisetine into the semi-cucurbit [6] urea solution, stirring for 2 days at 50 ℃, concentrating under reduced pressure at 40 ℃ to remove the DMSO, and freeze-drying the concentrate at-40 ℃ to obtain the clathrate of the semi-cucurbit [6] urea and the equisetine, wherein the yield is 97%.
Example 5: dissolving 3mmol of semi-cucurbit [6] urea (R is H) in 25mL of triethanolamine, stirring at 20 ℃ until the semi-cucurbit [6] urea is dissolved, adding 8.5mmol of N-methylmercapto-equisetum base into the semi-cucurbit [6] urea solution, stirring at 20 ℃ for 3 days, concentrating at 40 ℃ under reduced pressure to remove the triethanolamine, and spray-drying the concentrate at 60 ℃ to obtain the clathrate of the semi-cucurbit [6] urea and the N-methylmercapto-equisetum base, wherein the yield is 96%.
Example 6: mixing 1mmol of semi-calabash [6]]Urea (R is C)6H12) Dissolving in 25mL acetone, stirring at 20 deg.C to dissolve, adding 9mmol anatabine to semi-cucurbita [6]]Stirring in urea solution at 20 deg.C for 6.5 days, concentrating at 56 deg.C under reduced pressure to remove acetone, and rotary steaming at 43 deg.C to obtain semi-cucurbit [6]]Inclusion complex of urea with anatabine in 97% yield.
Example 7: mixing 1mmol of semi-calabash [6]]Urea (R is OCOC)2H5) Dissolving in 25mL diethyl ether, stirring at 20 deg.C to dissolve, adding 2mmol 2, 3' -dipyridine to semi-cucurbit [6]]Adding urea solution, stirring at 60 deg.C for 1 day, concentrating under reduced pressure at 40 deg.C to remove diethyl ether, spray drying at 80 deg.C to obtain semi-calabash [6]]The clathrate of urea with 2, 3' -bipyridine was obtained in 95% yield.
Example 8: mixing 2mmol of semi-calabash [6]]Urea (R is C)6H12) Dissolving in 25mL of tert-butyl methyl ether, stirring at 20 deg.C to dissolve, adding 9mmol of demethyldiennicotin to semi-cucurbita [6]]Stirring in urea solution at 30 deg.C for 7 days, concentrating under reduced pressure at 60 deg.C to remove tert-butyl methyl ether, evaporating concentrate to dryness at 40 deg.C to obtain semi-cucurbit [6]]Inclusion complex of urea with methyldiennicotin in 88% yield.
Example 9: mixing 5mmol of semi-bottle gourd [6]]Urea (R is OC)3H5) Dissolving in 25mL formic acid, stirring at 20 deg.C to dissolve, adding 15mmol 2, 3' -dipyridine to semi-cucurbit [6]]Stirring in urea solution at 30 deg.C for 6 days, concentrating under reduced pressure at 35 deg.C to remove formic acid, evaporating concentrate at 50 deg.C to dryness to obtain semi-cucurbit [6]]The clathrate of urea with 2, 3' -bipyridine was obtained in 81% yield.
Example 10: mixing 7mmol of semi-calabash [6]]Urea (R is OCOC)2H5) Dissolving in 25mL formic acid-water solution (1: 1), stirring at 20 deg.C to dissolve, adding 11mmol demethyl diene nicotine into semi-cucurbit [6]]Stirring in urea solution at 30 deg.C for 5 days, concentrating under reduced pressure at 43 deg.C to remove formic acid-water, evaporating concentrate at 40 deg.C to dryness to obtain semi-cucurbit [6]]Inclusion of urea with demethyldiennicotin, yieldThe content was 99%.
Example 11: dissolving 5mmol of semi-cucurbit [6] urea (R is H) in 25mL of methanol-water (1: 1) solution, stirring at 20 ℃ until the solution is dissolved, adding 15mmol of 2,3 '-bipyridine into the semi-cucurbit [6] urea solution, stirring at 30 ℃ for 1.5 days, concentrating at 35 ℃ under reduced pressure to remove methanol-water, drying the concentrate at 50 ℃ by rotary evaporation to obtain the clathrate of the semi-cucurbit [6] urea and the 2, 3' -bipyridine, wherein the yield is 88%.
Example 12: mixing 7mmol of semi-calabash [6]]Urea (R is OC)3H5) Dissolving in 25mL diethyl ether-water (1: 1) solution, stirring at 20 deg.C to dissolve, adding 11mmol demethyldiennicotin to semi-cucurbit [6]]Stirring in urea solution at 30 deg.C for 5 days, concentrating under reduced pressure at 43 deg.C to remove ether-water, evaporating concentrate at 40 deg.C to dryness to obtain semi-cucurbit [6]]The clathrate of urea with demethyldiennicotin, yield 99%.
Example 13: mixing 5mmol of semi-bottle gourd [6]]Urea (R is C)6H12) Dissolving in 25mL tert-butyl methyl ether-water (1: 2), stirring at 20 deg.C to dissolve, adding 15mmol of N-methylmethanoidine to semi-cucurbit [6]]Stirring in urea solution at 30 deg.C for 7 days, concentrating under reduced pressure at 50 deg.C to remove tert-butyl methyl ether-water, and spray drying at 80 deg.C to obtain semi-cucurbita [6]]The clathrate of urea with N-methylmethacet-equisetine was obtained in 97% yield.
Example 14: dissolving 2mmol of semi-cucurbit [6] urea (R is H) in 25mL of N, N-diisopropylethylamine-water (2: 1) solution, stirring at 20 ℃ until the semi-cucurbit [6] urea is dissolved, adding 12mmol of equisetine into the semi-cucurbit [6] urea solution, stirring at 30 ℃ for 2.5 days, concentrating at 55 ℃ under reduced pressure to remove the N, N-diisopropylethylamine-water, and carrying out rotary evaporation drying on the concentrate at 60 ℃ to obtain the clathrate compound of the semi-cucurbit [6] urea and the equisetine, wherein the yield is 85%.
Example 15: half of 3mmol of calabash [6]]Urea (R is OC)3H5) Dissolving in 25mL DMF-water (1: 1) solution, stirring at 20 deg.C to dissolve, adding 6mmol nornicotine into semi-cucurbit [6]]Stirring in urea solution at 30 deg.C for 3 days, concentrating under reduced pressure at 60 deg.C to remove DMF-water, and freeze drying at-55 deg.C to obtain semi-cucurbit [6]]Urea andthe yield of the inclusion compound of nornicotine is 95 percent.
Claims (7)
1. A clathrate compound of semi-cucurbit [6] uril and tobacco alkaloid is characterized in that: contains tobacco alkaloid and semi-cucurbit [6] urea, wherein the molar ratio of the tobacco alkaloid to the semi-cucurbit [6] urea is 1-10: 1.
2. The clathrate of semi-cucurbit [6] urea with tobacco alkaloids according to claim 1, wherein: the structural formula of the semi-cucurbit [6] urea is as follows:
wherein R is selected from H, C2H5、OH、C6H12、OC3H5、OCOC2H5。
3. The clathrate of semi-cucurbit [6] urea with tobacco alkaloids according to claim 2, wherein: the tobacco alkaloid is selected from nicotine, nornicotine, dehydronornicotine, diennicotine, demethyldiennicotinyl, equisetine, N-methylequisetine, anatabine, N-methylanatabine, and 2, 3' -bipyridine.
4. The method for preparing the clathrate of semicircles [6] urea and tobacco alkaloids according to claim 1, characterized in that: dissolving semi-cucurbit [6] uril in a solvent, adding tobacco alkaloid into the semi-cucurbit [6] uril solution according to the molar ratio of the tobacco alkaloid to the semi-cucurbit [6] uril of 1-10: 1, sealing and stirring for 6-168 hours at 20-60 ℃ in a dark place, filtering, removing insoluble substances, concentrating at 40-60 ℃ under reduced pressure, and drying the concentrate to obtain the tobacco alkaloid clathrate compound.
5. The method for preparing the clathrate compound of semi-cucurbita [6] uril and tobacco alkaloid according to claim 4, wherein: the solvent is one or two of water, methanol, acetone, diethyl ether, tert-butyl methyl ether, triethanolamine, N-diisopropylethylamine, formic acid, DMF and DMSO.
6. The method for preparing the clathrate compound of semi-cucurbita [6] uril and tobacco alkaloid according to claim 4, wherein: the drying is one of rotary steaming drying, freeze drying and spray drying.
7. The use of the clathrate of semi-cucurbit [6] urea and tobacco alkaloid of claim 1 as a slow release additive in flavors and fragrances, tobacco, cosmetics, food, nutraceuticals.
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| US20080264433A1 (en) * | 2006-03-09 | 2008-10-30 | Postech Academy-Industry Foundation | Cucurbituril Added Cigarettes and Manufacturing Method Thereof |
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| US20080264433A1 (en) * | 2006-03-09 | 2008-10-30 | Postech Academy-Industry Foundation | Cucurbituril Added Cigarettes and Manufacturing Method Thereof |
| US20090253754A1 (en) * | 2007-12-04 | 2009-10-08 | Francesca Selmin | Fast dissolving films and coatings for controlled release of flavors, active pharmaceutical ingredients, food substances, and nicotine |
| CN111303995A (en) * | 2020-03-02 | 2020-06-19 | 云南佩林科技有限公司 | Clathrate compound of anion ring-opening cucurbituril and nicotine substances as well as preparation method and application thereof |
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