WO2007083908A1 - Procédé de préparation à haut rendement de decursinol à partir d'angelica gigas - Google Patents

Procédé de préparation à haut rendement de decursinol à partir d'angelica gigas Download PDF

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Publication number
WO2007083908A1
WO2007083908A1 PCT/KR2007/000251 KR2007000251W WO2007083908A1 WO 2007083908 A1 WO2007083908 A1 WO 2007083908A1 KR 2007000251 W KR2007000251 W KR 2007000251W WO 2007083908 A1 WO2007083908 A1 WO 2007083908A1
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WO
WIPO (PCT)
Prior art keywords
decursinol
extract
ether
fraction
polar
Prior art date
Application number
PCT/KR2007/000251
Other languages
English (en)
Inventor
Yong Jin Park
Joo Hwan Kim
Jin Sook Kim
Gyu Yong Song
Jee Hyun Lee
Hye Gwang Jeong
Dong Hee Kim
Mi Young Yun
Wen Yi Jin
In Sop Shim
Yong Seok Choi
Original Assignee
Yong Jin Park
Joo Hwan Kim
Jin Sook Kim
Gyu Yong Song
Jee Hyun Lee
Hye Gwang Jeong
Dong Hee Kim
Mi Young Yun
Wen Yi Jin
In Sop Shim
Yong Seok Choi
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Yong Jin Park, Joo Hwan Kim, Jin Sook Kim, Gyu Yong Song, Jee Hyun Lee, Hye Gwang Jeong, Dong Hee Kim, Mi Young Yun, Wen Yi Jin, In Sop Shim, Yong Seok Choi filed Critical Yong Jin Park
Publication of WO2007083908A1 publication Critical patent/WO2007083908A1/fr

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Classifications

    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16N—LUBRICATING
    • F16N7/00—Arrangements for supplying oil or unspecified lubricant from a stationary reservoir or the equivalent in or on the machine or member to be lubricated
    • 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
    • C07D493/04—Ortho-condensed systems
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16N—LUBRICATING
    • F16N3/00—Devices for supplying lubricant by manual action
    • F16N3/02—Devices for supplying lubricant by manual action delivering oil
    • F16N3/04—Oil cans; Oil syringes
    • F16N3/06—Oil cans; Oil syringes delivering on squeezing
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16N—LUBRICATING
    • F16N2210/00—Applications
    • F16N2210/14—Bearings

Definitions

  • the present invention relates to novel method for preparing decursinol from angelica gigas with high yield.
  • Decursin has been reported to show potent anti-cancer effect on cancer cell while less cyto-toxic effect on normal cell than cancer cell, of which activity endows decursin with usefulness as a potent anti-cancer agent. Conventionally, it has been isolated from an ether soluble extract of Angelica decursiva Fr. St Sav. However, there have been to develop novel methods to obtain large amount of decursin in order to use as an anti-cancer agent and to synthesize decursinol in order to use as a precursor of decursin derivatives. Decursinol derivatives have been expected to be developed as a drug to treat leukemia or to alleviate nephro-toxicity.
  • the present invention provides a novel method for preparing decursinol from angelica gigas with high yield. [9]
  • the present invention provides novel method for preparing decursinol
  • St at 1 st step suspending and fractionating the extract with non-polar organic solvent selected from ether, chloroform, ethylacetate or acetone, preferably, ether solvent to obtain the non-polar soluble extract at 2 nd step; subjecting the non- polar soluble extract to basic hydrolysis with base selected from sodium hydroxide, potassium hydroxide, potassium carbonate or sodium carbonate, preferably, sodium hydroxide to obtain hydrolyzed product at 3 r step; neutralizing the solution with acid and recovering hydrolyzed decursinol fraction from the solution with non-polar organic solvent selected from ether, chloroform, methylene chloride, ethyl acetate or acetone at 4 th step; purifying the fraction to obtain purposed decursinol with high-yield.
  • non-polar organic solvent selected from ether, chloroform, ethylacetate or acetone, preferably, ether solvent to obtain the non-polar soluble extract at 2 nd step
  • base selected from sodium hydroxide,
  • the extraction solvent may be used 1 to 10 fold weight, preferably, 1 to 5 fold weight of C 1 -C 4 lower alcohol selected from water, methanol, ethanol and butanol, or the mixture thereof, preferably ethanol or the mixture of water and ethanol or water with the mixed ratio ranging from 1:01. to 1:10 (v/v) and the extraction may be performed with the extraction method selected from heat extraction, enfleurage extraction, hot-water extraction, reflux extraction, or sonication extraction, preferably, heat extraction for the period ranging from 0.5 to 20 hours, preferably, 7 to 13 hours, 1 to 10 times, preferably, 2 to 5 times.
  • the extraction method selected from heat extraction, enfleurage extraction, hot-water extraction, reflux extraction, or sonication extraction, preferably, heat extraction for the period ranging from 0.5 to 20 hours, preferably, 7 to 13 hours, 1 to 10 times, preferably, 2 to 5 times.
  • the base in the reaction may added to the non-polar soluble extract in an amount of ranging from 1 to 50g, preferably, 10 to 30g based on the weight of the extract (78g) and the reaction is preferably performed with stirring for the period ranging from 5 to 30 hours, preferably 10 to 15 hours to complete purposed hydrolysis.
  • distilled water is added to said hydrolysate and the solution is fractionated to recover water layer.
  • the water layer is adjusted to pH 2 with acid selected from hydrochloric acid.
  • the hydrolyzed decursinol fraction is extracted with non-polar organic solvent selected from ether, chloroform, ethylacetate or acetone, preferably, methylene chloride 1 to 7 times, preferably, 2 to 4 times and dehydrated to recover decursinol fraction.
  • the decursinol fraction is treated with active carbon in an amount of ranging from 1 to 50g, preferably, 10 to 2Og based on the volume of the fraction (300ml) and stirred for the period ranging from 10 to 60 hours, preferably 20 to 40 hours.
  • the solution is filtered and the filtrate is dried with vaccuo.
  • the dried filtrate is recrystallized with methanol to obtain purposed purified decursinol of the present invention.
  • the method for preparing decursinol disclosed herein shows superior advantage over conventional preparation of decursinol, for example, the method of the present invention overcome the disadvantages or problems of conventional method due to their favorable advantages comparing with conventional methods, i.e., lower production cost, simpler step, easier to mass production etc.
  • decursinol prepared by the procedure disclosed herein may be used as a precursor of decursin derivatives which can be useful in treating or preventing cancer disease, brain function disorder, nephro-toxic disease, diabetic hypertension and so on.
  • decursinol prepared by the procedure disclosed herein may be used as a precursor of decursin derivatives which can be useful in treating or preventing cancer disease, brain function disorder, nephro-toxic disease, diabetic hypertension and so on.
  • Example 1-3 The reactant prepared in Example 1-3 was transferred to 3 liter of separatory funnel and 1 liter of distilled water was added thereto to recover water layer.
  • the recovered water layer was transferred to 3 liter of separatory funnel and adjusted to pH 2 with 6M hydrochloric acid.
  • the water layer was subjected to repeating extraction with 800 ml, 500 ml and 500 ml of methylene chloride and the methylene chloride soluble layer was dehydrated with anhydrous glauber salt.
  • Example 5 Preparation of decursinol (5) [66] All the procedure was identical to that disclosed in Example 1 excepting that the concentrated ether soluble fraction was dissolved in 1 liter of methanol to perform hydrolysis disclosed in Example 1-3 as a base.
  • Example 6 Preparation of decursinol (6) [70] [71] All the procedure was identical to that disclosed in Example 1 excepting that the concentrated ether soluble fraction was added to separatory funnel and subjected to hydrolysis with 500 ml of 10% sodium hydroxide solution for 30 mins to extract twice disclosed in Example 1-3.
  • Example 7 Yield difference of decursinol according to various base [74] [75] The yield of decursinol prepared in Examples varying different base was determined to find appropriate base to perform hydrolysis.
  • the novel method for preparing decursinol from Angelica decursiva Fr. St disclosed herein could overcome the disadvantages or problems of conventional method due to their favorable advantages comparing with conventional methods, i.e., lower production cost, simpler step, easier to mass production etc and may be used as a precursor of decursin derivatives which can be useful in treating or preventing cancer disease, brain function disorder, nephro-toxic disease, diabetic hypertension and so on.

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  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Mechanical Engineering (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un nouveau procédé de préparation de decursinol (7-hydroxy-8,8-dimethyl-7,8-dihydro-6H-pyrano(3,2-)chromen-2-one) comportant : - une première étape qui consiste à effectuer l'extraction de racines sèches d'Angelica decursiva Fr. St, avec de l'eau, de l'alcool de faible poids moléculaire ou leur mélange et à filtrer et concentrer le filtrat pour obtenir l'extrait de racine d'Angelica decursiva Fr. St ; - une deuxième étape qui consiste à effectuer la suspension et le fractionnement de l'extrait avec un solvant organique non-polaire sélectionné parmi un éther, un chloroforme, un éthylacétate ou un solvant acétone pour obtenir l'extrait soluble non-polaire ; une troisième étape qui consiste à effectuer l'hydrolyse basique de l'extrait soluble non polaire avec une base sélectionnée parmi un hydroxyde de sodium, un hydroxyde de potassium, un carbonate de potassium ou un carbonate de sodium pour obtenir un produit hydrolysé ; une quatrième étape qui consiste à effectuer la neutralisation de la solution avec de l'acide et la récupération de la fraction de decursinol hydrolysée de la solution avec un solvant organique non-polaire sélectionné parmi un éther, un chloroforme, un chlorure de méthylène, un éthylacétate ou un acétone ; et enfin la purification de la fraction pour obtenir le decursinol souhaité avec un haut rendement.
PCT/KR2007/000251 2006-01-19 2007-01-16 Procédé de préparation à haut rendement de decursinol à partir d'angelica gigas WO2007083908A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020060005651A KR100715206B1 (ko) 2006-01-19 2006-01-19 참당귀로부터 데쿨시놀을 고수율로 제조하는 방법
KR10-2006-0005651 2006-01-19

Publications (1)

Publication Number Publication Date
WO2007083908A1 true WO2007083908A1 (fr) 2007-07-26

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PCT/KR2007/000251 WO2007083908A1 (fr) 2006-01-19 2007-01-16 Procédé de préparation à haut rendement de decursinol à partir d'angelica gigas

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KR (1) KR100715206B1 (fr)
WO (1) WO2007083908A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109846913A (zh) * 2019-03-27 2019-06-07 成都健腾生物技术有限公司 一种当归提取物的制备方法及其应用

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2753650T3 (es) 2014-06-30 2020-04-13 Nat Univ Pusan Ind Univ Coop Found Nuevo compuesto para inhibir la unión entre la proteína DX2 y la proteína p14/ARF, y composición farmacéutica para tratar o prevenir la enfermedad del cáncer que contiene el mismo como ingrediente efectivo
KR102556971B1 (ko) 2017-01-03 2023-07-19 주식회사 다산제약 데커시놀((+)-Decursinol)의 신규한 제조방법
KR102385511B1 (ko) 2019-03-22 2022-04-14 박재규 참당귀 추출물로부터 쿠마린 유도체의 합성방법

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20010086292A (ko) * 2000-01-24 2001-09-10 이희설 데커시놀 또는 이의 유도체를 포함하는 진통제 조성물
KR20020003928A (ko) * 2000-06-27 2002-01-16 조양호 참당귀로부터 뿌리배양을 이용하여 항암활성 물질데커시놀 안젤레이트를 생산하기 위한 배양, 추출 및분석방법
KR20030062058A (ko) * 2002-01-16 2003-07-23 주식회사 싸이젠하베스트 데커시놀을 유효성분으로 함유하는 숙취 해소용 조성물

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20010086292A (ko) * 2000-01-24 2001-09-10 이희설 데커시놀 또는 이의 유도체를 포함하는 진통제 조성물
KR20020003928A (ko) * 2000-06-27 2002-01-16 조양호 참당귀로부터 뿌리배양을 이용하여 항암활성 물질데커시놀 안젤레이트를 생산하기 위한 배양, 추출 및분석방법
KR20030062058A (ko) * 2002-01-16 2003-07-23 주식회사 싸이젠하베스트 데커시놀을 유효성분으로 함유하는 숙취 해소용 조성물

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109846913A (zh) * 2019-03-27 2019-06-07 成都健腾生物技术有限公司 一种当归提取物的制备方法及其应用

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