WO2007110168A1 - Curcumin synthesis - Google Patents

Curcumin synthesis Download PDF

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Publication number
WO2007110168A1
WO2007110168A1 PCT/EP2007/002403 EP2007002403W WO2007110168A1 WO 2007110168 A1 WO2007110168 A1 WO 2007110168A1 EP 2007002403 W EP2007002403 W EP 2007002403W WO 2007110168 A1 WO2007110168 A1 WO 2007110168A1
Authority
WO
WIPO (PCT)
Prior art keywords
curcumin
vanillin
acetylacetone
anyone
water
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.)
Ceased
Application number
PCT/EP2007/002403
Other languages
English (en)
French (fr)
Inventor
Christof Wehrli
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
DSM IP Assets BV
Original Assignee
DSM IP Assets BV
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 DSM IP Assets BV filed Critical DSM IP Assets BV
Priority to EP07723370A priority Critical patent/EP1999097B1/en
Priority to CN2007800198805A priority patent/CN101454267B/zh
Priority to JP2009501908A priority patent/JP5341747B2/ja
Priority to AT07723370T priority patent/ATE538080T1/de
Priority to US12/295,010 priority patent/US7964755B2/en
Publication of WO2007110168A1 publication Critical patent/WO2007110168A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
    • C07C45/74—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups combined with dehydration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
    • C07C49/24—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing hydroxy groups
    • C07C49/245—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing hydroxy groups containing six-membered aromatic rings
    • C07C49/248—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing hydroxy groups containing six-membered aromatic rings having unsaturation outside the aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
    • C07C49/255—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing ether groups, groups, groups, or groups

Definitions

  • the present invention relates to a synthesis of curcumin by condensation of vanillin with acetylacetone.
  • curcumin is obtained by reaction of vanillin in molten form (heating to 120-130°C) with acetylacetone in the presence of boric acid anhydride and a secondary amine and addition of glacial acetic acid, methanol and water. The yields are in the range of 19-28%.
  • vanillin is dissolved in dimethylsulfoxide, then boron oxide, acetylacetone and a secondary amine are added. After termination of the reaction at 80-85°C, aqueous acetic acid (5%) is added and after purification curcumin is obtained in a yield of 25% (purity 99.7%).
  • the present invention relates to a process for the preparation of curcumin by condensation of acetylacetone with vanillin in a highly polar, aprotic solvent, in the presence of boric acid and of an aliphatic or araliphatic amine, and subsequent work up, characterised in that vanillin in the presence of an equimolar or nearly equimolar amount of boric acid and a catalytic amount of a primary amine of the formula R - CH 2 - NH 2 , wherein R is C M 9 - alkyl or phenyl, optionally substituted with methyl, methoxy or halogen, in DMF, DMA or diglyme as solvent and, optionally, of an entrainer, is reacted with acetylacetone at a temperature of 50 - 85°C, preferably 50 - 60°C, at reduced pressure of 10 - 100 mbar, preferably 15 - 40 mbar, under concomitant removal of the reaction water by distillation
  • Example 4 Isolation by extraction and crystallisation
  • the reaction mixture according to Example 1 was dissolved in a reaction flask with Teflon blade stirrer, thermometer and a reflux cooler in 300 ml of ethylacetate.
  • the dark red solution was successively washed under reflux with 300ml 3% of acetic acid in water, followed by two washings with each 100ml of water.
  • the organic phase was evaporated to dryness at the rotavapor (70°C, 20 mbar).
  • the residue was suspended in 150 ml of methanol and refluxed for 30 minutes.
  • the suspension was cooled and stirred for 2 hours at ambient temperature.
  • the slurry was filtered with a Buchner funnel and washed with 50 ml of methanol.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
PCT/EP2007/002403 2006-03-29 2007-03-19 Curcumin synthesis Ceased WO2007110168A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP07723370A EP1999097B1 (en) 2006-03-29 2007-03-19 Curcumin synthesis
CN2007800198805A CN101454267B (zh) 2006-03-29 2007-03-19 姜黄素的合成
JP2009501908A JP5341747B2 (ja) 2006-03-29 2007-03-19 クルクミンの合成
AT07723370T ATE538080T1 (de) 2006-03-29 2007-03-19 Curcuminsynthese
US12/295,010 US7964755B2 (en) 2006-03-29 2007-03-19 Curcumin synthesis

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP06006519.0 2006-03-29
EP06006519 2006-03-29

Publications (1)

Publication Number Publication Date
WO2007110168A1 true WO2007110168A1 (en) 2007-10-04

Family

ID=38093544

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2007/002403 Ceased WO2007110168A1 (en) 2006-03-29 2007-03-19 Curcumin synthesis

Country Status (7)

Country Link
US (1) US7964755B2 (enExample)
EP (1) EP1999097B1 (enExample)
JP (1) JP5341747B2 (enExample)
KR (1) KR20080112340A (enExample)
CN (1) CN101454267B (enExample)
AT (1) ATE538080T1 (enExample)
WO (1) WO2007110168A1 (enExample)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010004579A3 (en) * 2008-07-07 2011-01-27 Laila Pharmaceuticals Pvt. Ltd. Orally active curcuminoid compounds
EP2568041A1 (en) 2007-12-27 2013-03-13 Baxter International Inc. Chemically modified factor IX
WO2013167770A1 (es) 2012-05-08 2013-11-14 Asac Compañía De Biotecnología E Investigacion Sa Procedimiento para la síntesis de curcumina

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102701934A (zh) * 2012-05-30 2012-10-03 江南大学 一种以氧化锌负载氧化镁为催化剂催化合成姜黄素的方法
CN102701933A (zh) * 2012-05-30 2012-10-03 江南大学 一种采用氧化铝负载氟化钾固体碱催化合成姜黄素的方法
CN102911022B (zh) * 2012-10-25 2015-12-09 山东鲁诺动物药业有限公司 一种天然姜黄素类物的人工合成方法
CN103910615A (zh) * 2014-04-09 2014-07-09 西安雅森生物技术有限公司 一种合成姜黄素的方法
CN108101761B (zh) * 2017-12-08 2021-08-03 陕西嘉禾生物科技股份有限公司 一种姜黄素的制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3194841A (en) * 1959-08-31 1965-07-13 Lever Brothers Ltd Process for preparing hepta-1:6-diene-3:5-diones
WO1997016403A1 (en) * 1995-11-03 1997-05-09 Geneprint, Inc. Process for the synthesis of curcumin-related compounds

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3821197A1 (de) * 1988-06-23 1989-12-28 Basf Ag Verfahren zur herstellung von (alpha),(beta)-ungesaettigten ketonen

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3194841A (en) * 1959-08-31 1965-07-13 Lever Brothers Ltd Process for preparing hepta-1:6-diene-3:5-diones
WO1997016403A1 (en) * 1995-11-03 1997-05-09 Geneprint, Inc. Process for the synthesis of curcumin-related compounds

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2568041A1 (en) 2007-12-27 2013-03-13 Baxter International Inc. Chemically modified factor IX
WO2010004579A3 (en) * 2008-07-07 2011-01-27 Laila Pharmaceuticals Pvt. Ltd. Orally active curcuminoid compounds
JP2011527340A (ja) * 2008-07-07 2011-10-27 ライラ ファーマシューティカルズ ピーブイティ．エルティディ． 経口活性クルクミノイド化合物
US8680143B2 (en) 2008-07-07 2014-03-25 Laila Pharmaceuticals Pvt. Ltd. Orally active curcuminoid compounds
WO2013167770A1 (es) 2012-05-08 2013-11-14 Asac Compañía De Biotecnología E Investigacion Sa Procedimiento para la síntesis de curcumina
EP2857379A4 (en) * 2012-05-08 2016-05-25 Asac Compañía De Biotecnología E Investigación Sa PROCESS FOR SYNTHESIS OF CURCUMINE

Also Published As

Publication number Publication date
CN101454267B (zh) 2012-09-26
KR20080112340A (ko) 2008-12-24
ATE538080T1 (de) 2012-01-15
CN101454267A (zh) 2009-06-10
EP1999097A1 (en) 2008-12-10
EP1999097B1 (en) 2011-12-21
US7964755B2 (en) 2011-06-21
US20100312015A1 (en) 2010-12-09
JP2009531353A (ja) 2009-09-03
JP5341747B2 (ja) 2013-11-13

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