WO2019057220A1 - 一种新型化合物及其制备方法 - Google Patents

一种新型化合物及其制备方法 Download PDF

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WO2019057220A1
WO2019057220A1 PCT/CN2018/115649 CN2018115649W WO2019057220A1 WO 2019057220 A1 WO2019057220 A1 WO 2019057220A1 CN 2018115649 W CN2018115649 W CN 2018115649W WO 2019057220 A1 WO2019057220 A1 WO 2019057220A1
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novel compound
methanol
water
organic solvent
extraction
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PCT/CN2018/115649
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French (fr)
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阮俊
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广西久福生物科技有限公司
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Priority to CA3076282A priority Critical patent/CA3076282C/en
Publication of WO2019057220A1 publication Critical patent/WO2019057220A1/zh
Priority to US16/808,371 priority patent/US10849934B2/en
Priority to US16/917,897 priority patent/US11000555B2/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/08—Bridged systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/618—Molluscs, e.g. fresh-water molluscs, oysters, clams, squids, octopus, cuttlefish, snails or slugs
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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    • 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
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/36—Opioid-abuse
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/334—Foods, ingredients or supplements having a functional effect on health treating the effects of consuming alcohol, narcotics or other addictive behavior, e.g. treating hangover or reducing blood alcohol levels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/37—Extraction at elevated pressure or temperature, e.g. pressurized solvent extraction [PSE], supercritical carbon dioxide extraction or subcritical water extraction
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids

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  • the invention belongs to the field of biomedical chemistry, and particularly relates to a novel compound and a preparation method thereof.
  • ⁇ also known as ⁇ , is the dry whole of the footer Vaginulus alte (Ferussac). Vaginulalte (Ferussac); "Guangxi Zhuang Medicine Quality Standards Volume II", [sexual taste and returning] Chinese medicine salty, cold. Return to the lungs, liver, and large intestine. Zhuang doctor salty, cold. [Functions and Indications] Chinese medicine hurricane fixed shock, clearing away heat and detoxification, reducing swelling and pain. For stroke Secluded, tendons, convulsions, wheezing, wheezing, throat, bloated, erysipelas, sputum nucleus, hemorrhoids swelling, pain, prolapse.
  • the object of the present invention is to provide a novel compound and provide a new idea for research and development of traditional Chinese medicine detoxification products.
  • the novel compound has the molecular formula: C 3 0H 52 O 7 ; molecular weight is 524; melting point: 248-249 ° C; solubility: white needle-like or columnar crystal, insoluble in water, insoluble in acid, alkali, easy Soluble in methanol, acetone, soluble in ethanol, ethyl acetate, hot chloroform, slightly soluble in cold chloroform; chiral C configuration includes: C3, R; C6, S; C7, S; C10, S; C11, R; C12, R; C13, R; C14, R; C15, S; C18, S; C19, S; C22, R.
  • novel compound is obtained by extracting and separating from sputum.
  • the crucible includes Vaginulus alte (Ferussac), Limax maximus L., L. flavus L., Agriolimaxagrestis L., and double One or more of Phiolomycus bilineatus.
  • a method of preparing a novel compound as described above comprising the steps of:
  • the lotus root powder is put into a supercritical CO2 extractor for extraction to obtain an extract;
  • reaction solution A is added to the organic solvent extraction, the organic solvent layer is separated, washed with water until the water washing solution is neutral, the organic solvent layer is separated, and the organic solvent is recovered under reduced pressure to obtain a thick paste A;
  • the conditions of supercritical CO2 extraction under the step S2 are: pressure 25KPa, temperature 65 ° C, flow rate 400-500 PV, extraction time 4 h; the organic solvent under the step S4 includes diethyl ether, One or two of ethyl acetate and n-butanol.
  • a method of preparing a novel compound as described above comprising the steps of:
  • reaction solution B is added to an organic solvent for extraction, the organic solvent layer is separated, washed with water until the water washing solution is neutral, the organic solvent layer is separated, and the organic solvent is recovered under reduced pressure to obtain a thick paste C;
  • T5 adding methanol to the thick paste C, heating and dissolving, filtering, the filtrate is allowed to cool, standing, crystallizing, and the mother liquid is reserved;
  • T6 taking the crystal, the novel compound is obtained by preparative medium pressure liquid phase separation, the liquid phase condition is: reversed phase C18 column, the solvent system is methanol: acetonitrile: isopropanol: water (70:20:6:4) The flow rate is 50 ml/mun.
  • the organic solvent in the preparation method of the above novel compound in the step T2 includes n-hexane, ethanol, methanol, acetone, chloroform, oil, gasoline, petroleum ether, n-butanol, diethyl ether and ethyl acetate.
  • esters and the like One or two of esters and the like.
  • a method for preparing a novel compound as described above further comprising the steps of: taking a mother liquor under S5 or T5, adding water in a ratio of methanol:water (8:2), heating to reflux, separating a black oil, and filtering the methanol solution.
  • the methanol is recovered, dried, and the residue is added to chloroform to be dissolved, cooled, and the crystals are allowed to stand for precipitation.
  • the crystals are washed with a small amount of methane chloride, dried, added with methanol, dissolved by heating, cooled, crystallized, filtered, dried.
  • the novel compound is obtained.
  • the novel compound of the present invention is obtained by extracting from a traditional Chinese medicine by a simple method.
  • the compound has the effects of sedative and hypnotic effects, has significant effects on physiological and mental dependence on detoxification or detoxification, and is useful for preparing detoxification or detoxification drugs, and has potential application value.
  • Figure 1 is an X-ray crystal structure of a novel compound of the present invention.
  • Figure 2 is a perspective view of the crystal space of the novel compound of the present invention.
  • Figures 3 and 4 are crystal forms of the novel compounds of the present invention.
  • Figures 5 to 11 are NMR nuclear magnetic resonance carbon (C) hydrogen (H) spectra of the novel compounds of the present invention.
  • Figures 12-14 are mass spectrometry (MS) data plots of the novel compounds of the present invention.
  • the invention provides a novel compound whose specific structure is:
  • a method for preparing a novel compound comprising the steps of:
  • reaction liquid A is added to diethyl ether extraction, the ether layer is separated, washed with water until the water washing liquid is neutral, the ether layer is separated, and the ether is recovered under reduced pressure to obtain a thick paste A;
  • a method for preparing a novel compound comprising the steps of:
  • T1 ⁇ 100kg, net selection, impurity removal, pulverization into 20 mesh coarse powder, spare;
  • T2 take the coarse powder, put it into the multi-function extraction tank, add the solvent to the reflux of n-hexane to extract 2 times, filter, combine the extract, recover the n-hexane under reduced pressure to obtain thick paste B;
  • the saponification reaction time is 3.5 h, and the reaction liquid B is obtained;
  • reaction solution B was added to ethyl acetate for extraction, and the ethyl acetate solution was separated, washed with deionized water until the water washing solution was neutral, and then the ethyl acetate solution was separated, and ethyl acetate was evaporated under reduced pressure to obtain a thick paste C. ;
  • T5 adding methanol to the thick paste C, heating and dissolving, filtering, the filtrate is allowed to cool, standing, crystallizing, and the mother liquid is reserved;
  • T6 taking crystals, and obtaining a novel compound by preparative medium-pressure liquid phase separation, the liquid phase condition is: reversed phase C18 column, solvent system is methanol: acetonitrile: isopropanol: water (70:20:6:4), flow rate Is 50ml/mun;
  • T7 Take methanol mother liquor under T5, add deionized water according to methanol: water (8:2), heat reflux, precipitate black oil, filter methanol solution, recover methanol, dry, and add residue to chloroform to dissolve. After cooling, the crystals are precipitated and filtered, and the crystals are washed with a small amount of methylene chloride, dried, methanol is added, dissolved by heating, cooled, allowed to stand, crystals are precipitated, filtered, and dried to give a novel compound.
  • a method for preparing a novel compound comprising the steps of:
  • T1 take 150kg, clean, remove impurities, pulverize into 20 mesh coarse powder, spare;
  • T4 The reaction solution B is added to n-butanol extraction, the n-butanol solution is separated, washed with deionized water until the water washing solution is neutral, the n-butanol solution is separated, and n-butanol is recovered under reduced pressure to obtain a thick paste C;
  • T5 adding methanol to the thick paste C, heating and dissolving, filtering, the filtrate is allowed to cool, standing, crystallizing, and the mother liquid is reserved;
  • T6 taking the crystal, the novel compound is obtained by preparative medium pressure liquid phase separation, the liquid phase condition is: reversed phase C18 column, the solvent system is methanol: acetonitrile: isopropanol: water (70:20:6:4) , the flow rate is 50ml / mun;
  • T7 Take the mother liquor under T5, add deionized water according to methanol: water (8:2), heat reflux, precipitate black oil, filter methanol solution, recover methanol, dry, add residue to chloroform to dissolve and cool The crystals are allowed to stand still and filtered, and the crystals are washed with a small amount of methylene chloride, dried, added with methanol, dissolved by heating, cooled, allowed to stand, crystallized, filtered, and dried to give a novel compound.
  • a method for preparing a novel compound comprising the steps of:
  • T1 Take 100kg, clean, remove impurities, pulverize into 20 mesh coarse powder, and set aside;
  • T2 take the coarse powder, put it into the multi-function extraction tank, add methanol reflux to extract 2 times, filter, combine the extract, recover the methanol under reduced pressure to obtain thick paste B;
  • T5 adding methanol to the thick paste C, heating and dissolving, filtering, the filtrate is allowed to cool, standing, crystallizing, and the mother liquid is reserved;
  • T6 taking the crystal, the novel compound is obtained by preparative medium pressure liquid phase separation, the liquid phase condition is: reversed phase C18 column, the solvent system is methanol: acetonitrile: isopropanol: water (70:20:6:4) , the flow rate is 50ml / mun;
  • T7 Take the mother liquor under T5, add deionized water according to methanol: water (8:2), heat reflux, precipitate black oil, filter methanol solution, recover methanol, dry, add residue to chloroform to dissolve, cool The crystals are allowed to stand still and filtered, and the crystals are washed with a small amount of methylene chloride, dried, added with methanol, dissolved by heating, cooled, allowed to stand, crystallized, filtered, and dried to give a novel compound.
  • a method for preparing a novel compound comprising the steps of:
  • reaction liquid A is extracted with ethyl acetate, and the ethyl acetate layer is separated, washed with water until the water washing liquid is neutral, the ethyl acetate layer is separated, and the ethyl acetate is recovered under reduced pressure to obtain a thick paste A;

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Abstract

公开了一种新型化合物，该新型化合物从蛞蝓中提取分离制得，还公开了该新型化合物的提取分离方法，该方法简便、易操作。该新型化合物具有镇静催眠的作用，对生理性、精神性依赖脱毒或戒毒的效果显著，用于制备脱毒或戒毒药物，具有潜在的应用价值，为进一步开发蛞蝓戒毒药品提供新思路。

Description

一种新型化合物及其制备方法 技术领域
本发明属于生物医药化学领域，具体涉及一种新型化合物及其制备方法。
背景技术
蛞蝓，又名碾沐，为足襞蛞蝓科动物覆套足襞蛞蝓Vaginulus alte(Ferussac)的干燥全体。覆套足襞蛞(Vaginulalte(Ferussac))；《广西壮药质量标准第二卷》，【性味与归经】中医咸，寒。归肺、肝、大肠经。壮医咸，寒。【功能与主治】中医祛风定惊，清热解毒，消肿止痛。用于中风
Figure PCTCN2018115649-appb-000001
僻，筋脉拘挛，惊痫，喘息，咽肿，喉痹，痈肿，丹毒，痰核，痔疮肿痛，脱肛。壮医清热毒，调气道，通龙路。用于货烟妈(咽炎)、墨病(哮喘)，尊寸(脱肛)，兵嘿细勒(疝气)，呗农(痈疮)，京瑟(闭经)，蜈蚣咬伤。
现有技术对蛞蝓在抗菌、抗癌方面有广泛的研究，而目前，经过研究发现中药蛞蝓提取物有明显的镇静催眠作用，对吗啡和苯丙胺引起的小鼠兴奋性具有一定抑制作用，对吗啡依赖大鼠戒断症状具有脱毒治疗效果，且急性毒性安全，无生理和精神依赖性，若能进一步研究蛞蝓提取物中戒毒成分物质，明确其性状，这对进一步开发中药戒毒产品，具有重要的意义。
发明内容
本发明的目的是提供一种新型化合物，为研究开发中药戒毒产品提供新思路。
本发明采用以下技术方案：
一种新型化合物，其结构为
Figure PCTCN2018115649-appb-000002
进一步的，所述新型化合物的分子式为：C 30H 52O 7；分子量为524；熔点：248～ 249℃；溶解性：白色针状或柱状结晶，不溶于水，不溶于酸、碱，易溶于甲醇、丙酮、溶于乙醇、乙酸乙酯、热三氯甲烷，微溶于冷三氯甲烷；手性C构型包括：C3，R；C6，S；C7，S；C10，S；C11，R；C12，R；C13，R；C14，R；C15，S；C18，S；C19，S；C22，R。
进一步的，所述新型化合物从蛞蝓中提取分离制得。
更进一步的，所述蛞蝓，包括覆套足襞蛞蝓(Vaginulus alte(Ferussac))、大蛞蝓(Limax maximus L.)、黄蛞蝓(L.flavus L.)、野蛞蝓(Agriolimaxagrestis L.)和双线粘液蛞蝓(Phiolomycus bilineatus)中的一种或多种。
一种如上所述新型化合物的制备方法，包括以下步骤：
S1.将蛞蝓粉碎得蛞蝓粉；
S2.将蛞蝓粉投入至超临界CO2萃取器中萃取，制得萃取物；
S3.将萃取物、氢氧化钾和水按照重量比“萃取物:氢氧化钾:水＝1:1:1.5”加入反应釜中，混匀，加热搅拌发生皂化反应，制得反应液A；
S4.将反应液A加入有机溶剂萃取，分取有机溶剂层，用水洗涤至水洗液呈中性后，分取有机溶剂层，减压回收有机溶剂，得稠膏A；
S5：在稠膏A中加入甲醇，加热溶解，过滤，滤液放冷，静置，析出结晶，母液备用；
S6：取结晶，通过制备型中压液相分离得到所述新型化合物，液相条件为：反相C18柱，溶剂系统为甲醇:乙腈:异丙醇:水(70:20:6:4)，流速为50ml/mun。
进一步的，以上所述新型化合物，步骤S2项下所述超临界CO2萃取的条件为：压力25KPa，温度65℃，流量400～500PV，萃取时间4h；步骤S4项下所述有机溶剂包括乙醚、乙酸乙酯和正丁醇等中的一种或两种。
一种如上所述新型化合物的制备方法，包括以下步骤：
T1.将蛞蝓粉碎得蛞蝓粉；
T2.将蛞蝓粉投入至多功能提取罐中，加入有机溶媒回流提取，过滤，提取液减压回收有机溶媒，制得稠膏B；
T3.将稠膏B、氢氧化钾和水按照重量比“萃取物:氢氧化钾:水＝1:1:1.5”加入反应釜中，混匀，加热搅拌发生皂化反应，制得反应液B；
T4.将反应液B加入有机溶剂萃取，分取有机溶剂层，用水洗涤至水洗液呈中性后，分取有机溶剂层，减压回收有机溶剂，得稠膏C；
T5：在稠膏C中加入甲醇，加热溶解，过滤，滤液放冷，静置，析出结晶，母液备用；
T6：取结晶，通过制备型中压液相分离得到所述新型化合物，液相条件为：反相C18柱，溶剂系统为甲醇:乙腈:异丙醇:水(70:20:6:4)，流速为50ml/mun。
进一步的，以上所述新型化合物的制备方法中步骤T2项下所述有机溶媒包括正已烷、乙醇、甲醇、丙酮、三氯甲烷、油、汽油、石油醚、正丁醇、乙醚和乙酸乙酯等中的一种或两种。
一种如上所述新型化合物的制备方法，还包括以下步骤：取S5或T5项下母液，按甲醇:水(8:2)比例加入水，加热回流，析出黑色油状物，滤取甲醇溶液，回收甲醇，干燥，残渣加入三氯甲烷加热使溶解、冷却，静置析出结晶，过滤，得结晶体用少量三氯化甲烷洗涤，干燥，加入甲醇，加热溶解，冷却，析出结晶，过滤，干燥，得到所述新型化合物。
本发明的新型化合物采用简便的方法从中药蛞蝓中提取而得。所述化合物具有镇静催眠的作用，对生理性、精神性依赖脱毒或戒毒的效果显著，用于制备脱毒或戒毒药物，具有潜在的应用价值。
附图说明
1、图1为本发明新型化合物的X射线晶体结构。
2、图2为本发明新型化合物的晶体空间立体结构图。
3、图3、图4为本发明新型化合物的晶形图。
4、图5-图11为本发明新型化合物的NMR核磁共振碳(C)氢(H)谱。
5、图12-图14为本发明的新型化合物的质谱(MS)数据图。
具体实施方式
一、一种新型化合物
实施例1
本发明提供了一种新型化合物，其具体结构为：
Figure PCTCN2018115649-appb-000003
所述化合物的具体信息如下：
(1)该化合物命名为“蛞蝓素”，其英文名为：limaxol A。
(2)化合物中的手性C构型：C3,R；C6,S；C7,S；C10,S；C11,R；C12,R；C13,R；C14,R；C15,S；C18,S；C19,S；C22,R.，其晶体结构图如图1、图2所示。
(3)其物理化学性质及光谱数据：
①分子式：C30H52O7；分子量524。
②状态：白色针(柱)状结晶(结晶溶剂：甲醇)，其结晶图见图3、图4。
③熔点：248～249℃。
④溶解性：白色针(柱)状结晶，不溶于水，不溶于酸、碱，易溶于甲醇、丙酮、溶于乙醇、乙酸乙酯、三氯甲烷(热)，微溶于三氯甲烷(冷)。
⑤NMR核磁共振碳(C)氢(H)谱数据如表1，NMRNMR核磁共振碳(C)氢(H)谱如图5-图11
表1
Figure PCTCN2018115649-appb-000004
⑥质谱(MS)数据图，如图12～图14，
二、一种新型化合物的制备方法
实施例2
一种新型化合物的制备方法，包括以下步骤：
S1：取蛞蝓60kg，净选，除杂，粉碎成20目粗粉，备用；
S2：取蛞蝓粗粉，投入至超临界CO2萃取器中萃取，萃取条件为压力25PKa，温度65℃，流量400PV，萃取时间4h，得萃取物；
S3：将萃取物、氢氧化钾和水按照重量比“萃取物:氢氧化钾:水＝1:1:1.5”加入反应釜中，混匀，加热温度至85℃，边搅拌边反应，皂化反应时间2h，得皂化反应液A；
S4：将反应液A加入乙醚萃取，分取乙醚层，用水洗涤至水洗液呈中性后，分取乙醚层，减压回收乙醚，得稠膏A；
S5：在稠膏A中，加入甲醇，加热溶解，过滤，滤液静置，析出结晶，母液备用；
S6：取结晶，通过制备型中压液相分离得到新型化合物，液相条件为：反相C18柱，溶剂系统为甲醇:乙腈:异丙醇:水(70:20:6:4)，流速为50ml/mun；
S7：取S5项下母液，按甲醇：水(8:2)加入去离子水，加热回流，析出黑色油状物，滤取甲醇溶液，回收甲醇，干燥，残渣加入三氯甲烷，加热使溶解，冷却，静置析出结晶，过滤，得结晶体用少量三氯化甲烷洗涤，干燥，加入甲醇， 加热溶解，冷却，静置，析出结晶，过滤，干燥，得到新型化合物。
实施例3
一种新型化合物的制备方法，包括以下步骤：
T1：将蛞蝓100kg，净选，除杂，粉碎成20目粗粉，备用；
T2：取蛞蝓粗粉，投入至多功能提取罐中，加入溶剂正已烷回流提取2次，过滤，合并提取液，减压回收正已烷，得稠膏B；
T3：将稠膏B、氢氧化钾和水按照重量比“萃取物:氢氧化钾:水＝1:1:1.5”加入反应釜中，混匀，加热温度至95℃，边搅拌边反应，皂化反应时间3.5h，得反应液B；
T4：将反应液B加入乙酸乙酯萃取，分取乙酸乙酯液，用去离子水洗涤至水洗液呈中性后，分取乙酸乙酯液，减压回收乙酸乙酯，得稠膏C；
T5：在稠膏C中加入甲醇，加热溶解，过滤，滤液放冷，静置，析出结晶，母液备用；
T6：取结晶，通过制备型中压液相分离得到新型化合物，液相条件为：反相C18柱，溶剂系统为甲醇:乙腈:异丙醇:水(70:20:6:4)，流速为50ml/mun；
T7：取T5项下甲醇母液，按甲醇：水(8:2)加入去离子水，加热回流，析出黑色油状物，滤取甲醇溶液，回收甲醇，干燥，残渣加入三氯甲烷加热使溶解，冷却，静析出结晶，过滤，得结晶体用少量三氯化甲烷洗涤，干燥，加甲醇，加热溶解，冷却，静置，析出结晶，过滤，干燥，得到新型化合物。
实施例4
一种新型化合物的制备方法，包括以下步骤：
T1：取蛞蝓150kg，净选，除杂，粉碎成20目粗粉，备用；
T2：取蛞蝓粗粉，投入至多功能提取罐中，加入混合溶剂(三氯甲烷：丙酮＝1：1)回流提取2次，过滤，合并提取液，减压回收溶剂，得稠膏B；
T3：将稠膏B、氢氧化钾和水按照重量比“萃取物:氢氧化钾:水＝1:1:1.5”加入反应釜中，混匀，加热温度至100℃，边搅拌边反应，皂化反应时间4h，得反应液B；
T4：将反应液B加入正丁醇萃取，分取正丁醇液，用去离子水洗涤至水洗液呈中性，分取正丁醇液，减压回收正丁醇，得稠膏C；
T5：在稠膏C中加入甲醇，加热溶解，过滤，滤液放冷，静置，析出结晶，母液备用；
T6：取结晶，通过制备型中压液相分离得到所述新型化合物，液相条件为：反相C18柱，溶剂系统为甲醇:乙腈:异丙醇:水(70:20:6:4)，流速为50ml/mun；
T7：取T5项下母液，按甲醇：水(8:2)加入去离子水，加热回流，析出黑色油状物，滤取甲醇溶液，回收甲醇，干燥，残渣加入三氯甲烷加热使溶解、冷却，静置析出结晶，过滤，得结晶体用少量三氯化甲烷洗涤，干燥，加甲醇，加热溶解，冷却，静置，析出结晶，过滤，干燥，得到新型化合物。
实施例5
一种新型化合物的制备方法，包括以下步骤：
T1：取蛞蝓100kg，净选，除杂，粉碎成20目粗粉，备用；
T2：取蛞蝓粗粉，投入至多功能提取罐中，加入甲醇回流提取2次，过滤，合并提取液，减压回收甲醇，得稠膏B；
T3：将稠膏B、氢氧化钾和水按照重量比“萃取物:氢氧化钾:水＝1:1:1.5”加入反应釜中，混匀，加热温度至90℃，边搅拌边反应，皂化反应时间3h，得反应液B；
T4：将反应液B加入混合溶剂(乙酸乙酯:乙醚＝1:1)萃取，分取混合溶剂层，合并，用去离子水洗涤至水洗液呈中性，分取混合溶剂层，减压回收溶剂，得稠膏C；
T5：在稠膏C中加入甲醇，加热溶解，过滤，滤液放冷，静置，析出结晶，母液备用；
T6：取结晶，通过制备型中压液相分离得到所述新型化合物，液相条件为：反相C18柱，溶剂系统为甲醇:乙腈:异丙醇:水(70:20:6:4)，流速为50ml/mun；
T7：取T5项下母液，按甲醇：水(8:2)加入去离子水，加热回流，析出黑色油状物，滤取甲醇溶液，回收甲醇，干燥，残渣加入三氯甲烷加热使溶解，冷 却，静置析出结晶，过滤，得结晶体用少量三氯化甲烷洗涤，干燥，加甲醇，加热溶解，冷却，静置，析出结晶，过滤，干燥，得到新型化合物。
实施例6
一种新型化合物的制备方法，包括以下步骤：
S1：取蛞蝓100kg，净选，除杂，粉碎成20目粗粉，备用；
S2：取蛞蝓粗粉，投入至超临界CO2萃取器中萃取，萃取条件为压力25PKa，温度65℃，流量500PV，萃取时间4h，得萃取物；
S3：将萃取物、氢氧化钾和水按照重量比“萃取物:氢氧化钾:水＝1:1:1.5”加入反应釜中，混匀，加热温度至100℃，边搅拌边反应，皂化反应时间4h，得皂化反应液A；
S4：将反应液A加入乙酸乙酯萃取，分取乙酸乙酯层，用水洗涤至水洗液呈中性后，分取乙酸乙酯层，减压回收乙酸乙酯，得稠膏A；
S5：在稠膏A中，加入甲醇，加热溶解，过滤，滤液静置，析出结晶，母液备用；
S6：取结晶，通过制备型中压液相分离得到新型化合物，液相条件为：反相C18柱，溶剂系统为甲醇:乙腈:异丙醇:水(70:20:6:4)，流速为50ml/mun；
S7：取S5项下母液，按甲醇：水(8:2)加入去离子水，加热回流，析出黑色油状物，滤取甲醇溶液，回收甲醇，干燥，残渣加入三氯甲烷，加热使溶解，冷却，静置析出结晶，过滤，得结晶体用少量三氯化甲烷洗涤，干燥，加入甲醇，加热溶解，冷却，静置，析出结晶，过滤，干燥，得到新型化合物。

Claims (11)

  1. 一种新型化合物，其特征在于，其结构为：
    Figure PCTCN2018115649-appb-100001
  2. 根据权利要求1所述新型化合物，其特征在于，所述新型化合物的分子式为：C 3OH 52O 7；分子量为524；熔点：248～249℃；溶解性：白色针状或柱状结晶，不溶于水，不溶于酸、碱，易溶于甲醇、丙酮、溶于乙醇、乙酸乙酯、热三氯甲烷，微溶于冷三氯甲烷。
  3. 根据权利要求1所述新型化合物，其特征在于，所述新型化合物手性C构型包括：C3，R；C6，S；C7，S；C10，S；C11，R；C12，R；C13，R；C14，R；C15，S；C18，S；C19，S；C22，R。
  4. 根据权利要求1所述新型化合物，其特征在于，所述新型化合物从蛞蝓中提取分离制得。
  5. 根据权利要求4所述新型化合物，其特征在于，所述蛞蝓，包括覆套足襞蛞蝓(Vaginulus alte(Ferussac))、大蛞蝓(Limax maximus L.)、黄蛞蝓(L.flavus L.)、野蛞蝓(Agriolimax agrestis L.)和双线粘液蛞蝓(Phiolomycus bilineatus)中的一种或多种。
  6. 一种如权利要求1所述新型化合物的制备方法，其特征在于，包括以下步骤：S1.将蛞蝓粉碎得蛞蝓粉；
    S2.将蛞蝓粉投入至超临界CO2萃取器中萃取，制得萃取物；
    S3.将萃取物、氢氧化钾和水按照重量比“萃取物:氢氧化钾:水＝1:1:1.5”加入反应釜中，混匀，加热搅拌发生皂化反应，制得反应液A；
    S4.将反应液A加入有机溶剂萃取，分取有机溶剂层，用水洗涤至水洗液呈中性后，分取有机溶剂层，减压回收有机溶剂，得稠膏A；
    S5：在稠膏A中加入甲醇，加热溶解，过滤，滤液放冷，静置，析出结晶， 母液备用；
    S6：取结晶，通过制备型中压液相分离得到所述新型化合物，液相条件为：反相C18柱，溶剂系统为甲醇:乙腈:异丙醇:水(70:20:6:4)，流速为50ml/mun。
  7. 根据权利要求6所述新型化合物的制备方法，其特征在于，所述有机溶剂包括乙醚、乙酸乙酯和正丁醇中的一种或两种。
  8. 一种如权利要求1所述新型化合物的制备方法，其特征在于，包括以下步骤：
    T1.将蛞蝓粉碎得蛞蝓粉；
    T2.将蛞蝓粉投入至多功能提取罐中，加入有机溶媒回流提取，过滤，提取液减压回收有机溶媒，制得稠膏B；
    T3.将稠膏B、氢氧化钾和水按照重量比“萃取物:氢氧化钾:水＝1:1:1.5”加入反应釜中，混匀，加热搅拌发生皂化反应，制得反应液B；
    T4.将反应液B加入有机溶剂萃取，分取有机溶剂层，用水洗涤至水洗液呈中性后，分取有机溶剂层，减压回收有机溶剂，得稠膏C；
    T5：在稠膏C中加入甲醇，加热溶解，过滤，滤液放冷，静置，析出结晶，母液备用；
    T6：取结晶，通过制备型中压液相分离得到所述新型化合物，液相条件为：反相C18柱，溶剂系统为甲醇:乙腈:异丙醇:水(70:20:6:4)，流速为50ml/mun。
  9. 根据权利要求7所述新型化合物的制备方法，其特征在于，所述有机溶媒包括正已烷、乙醇、甲醇、丙酮、三氯甲烷、油、汽油、石油醚、正丁醇、乙醚和乙酸乙酯中的一种或两种。
  10. 一种如权利要求1所述新型化合物的制备方法，其特征在于，还包括以下步骤：取S5或T5项下母液，按甲醇:水(8:2)比例加入水，加热回流，析出黑色油状物，滤取甲醇溶液，回收甲醇，干燥，残渣加入三氯甲烷加热使溶解，冷却，静置析出结晶，过滤，得结晶体用少量三氯化甲烷洗涤，干燥，加入甲醇，加热溶解，冷却，析出结晶，过滤，干燥，得到所述新型化合物。
  11. 根据权利要求6所述新型化合物，其特征在于，所述新型化合物通过超 临界CO2萃取法萃取时超临界CO2萃取的条件为：压力25KPa，温度65℃，流量400～500PV，萃取时间4h。
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