WO2002053562A1 - Derive d'acide cojique et son mode de preparation - Google Patents

Derive d'acide cojique et son mode de preparation Download PDF

Info

Publication number
WO2002053562A1
WO2002053562A1 PCT/KR2001/002298 KR0102298W WO02053562A1 WO 2002053562 A1 WO2002053562 A1 WO 2002053562A1 KR 0102298 W KR0102298 W KR 0102298W WO 02053562 A1 WO02053562 A1 WO 02053562A1
Authority
WO
WIPO (PCT)
Prior art keywords
substituted
salt
acid
group
anhydride
Prior art date
Application number
PCT/KR2001/002298
Other languages
English (en)
Inventor
Duck Hee Kim
Ho Sik Rho
Jae Won Yoo
Heung Soo Baek
Su Sun An
Jong Eoun Hong
Hak Hee Kang
Hyun Jung Shin
Eun Young Lee
Ih Seop Chang
Original Assignee
Pacific Corporation
Kim, Kil, Joong
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
Priority claimed from KR1020000085161A external-priority patent/KR100365072B1/ko
Priority claimed from KR10-2001-0076528A external-priority patent/KR100436014B1/ko
Application filed by Pacific Corporation, Kim, Kil, Joong filed Critical Pacific Corporation
Publication of WO2002053562A1 publication Critical patent/WO2002053562A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/34—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D309/36—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
    • C07D309/38—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms one oxygen atom in position 2 or 4, e.g. pyrones

Definitions

  • the present invention relates to new kojic acid derivatives represented by the following formula (1) and to preparation method thereof :
  • R is an alkyl group having 2 ⁇ 10 of carbon number substituted by a lower alkyl group having 1 ⁇ 6 of carbon number or not substituted; an alkenyl group having 2 ⁇ 10 of carbon number; a benzyl group substituted or not substituted; or a pyridine group substituted or not substituted).
  • a color of human skin is determined by various factors such as red blood corpuscles, carotene, melanin, et al, however the racial color difference or hyperpigmentation, for example mole and freckles is influenced by melanin.
  • Melanin exists in the outermost layer of the epidermis, i.e., stratum corneum, and blocks ultraviolet to protect skin tissues under the inner skin and captures free radicals to protect skin proteins and genes.
  • the melanin that formed by inner or outer stress and is very stable compound and is not removed from the human body until discharged by corneous tissue.
  • This melanin is formed by oxidative polymerization of tyrosine or DOPA with the catalytic action of tyrosinase, further it may be increased by free radicals of the skin, inflammation or ultraviolet. Particularly, ultraviolet accelerates the formation of melanin, which partially grows into moles having bad affect on the skin beauty. Unfortunately, it may grow into dangerous cutaneous cancer.
  • Tyrosinase is a very important enzyme involved in the formation of melanin and many researchers have made efforts to find materials inhibiting the action of tyrosinase.
  • kojic acid has a strong activity of inhibiting the action of tyrosinase.
  • many derivatives, especially, substituted with hydrophobic groups at 7-hydroxymethyl position have been synthesized. Usually, these derivatives have increased activities for inhibiting the action of tyrosinase, but have poor stability in comparison with that of kojic acid itself. Therefore, these derivatives could not be widely applied.
  • kojic acid derivatives substituted at 7-hydroxy position with other kojic acid by using connecting group exhibit improved tyrosinase-inhibiting activity and have better stability than that of kojic acid itself, as well as decreased side effects to human skin.
  • an object of the present invention is to provide a new kojic acid derivative represented by the following formula 1 and a preparation method thereof: [Formula 1]
  • R is an alkyl group having 2 ⁇ 10 of carbon number substituted by a lower alkyl group having 1 ⁇ 6 of carbon number or not substituted; an alkenyl group having 2 ⁇ 10 of carbon number; a benzyl group substituted or not substituted; or a pyridine group substituted or not substituted).
  • the present invention provides a kojic acid derivative represented by the following formula 1 : [Formula 1]
  • R is an alkyl group having 2 ⁇ 10 of carbon number substituted by a lower alkyl group having 1 ⁇ 6 of carbon number or not substituted; an alkenyl group having 2 ⁇ 10 of carbon number; a benzyl group substituted or not substituted; or a pyridine group substituted or not substituted).
  • said benzyl group may be C 6 H 4 -1,4-, C 6 H 4 -1,3-, etc.
  • said pyridine group may be C 5 H 3 N-2,5-, C 5 H 3 N-3,5-, etc.
  • the present kojic acid derivative may be prepared by either of the following two processes according to R of said formula 1. One is employing dicarboxylic anhydride, and the other is employing chloride such as thionyl chloride.
  • the first method for preparing the present kojic acid derivative comprises the following steps.
  • the first method may be preferably applied to a preparation of the derivatives of which R is an alkyl group having 2 ⁇ 10 of carbon number, an alkyl group having 2 ⁇ 10 of carbon number substituted by a lower alkyl group having 1 ⁇ 6 of carbon number or an alkenyl group having 2 ⁇ 10 of carbon number.
  • reaction Scheme 1 [Reaction Scheme 1]
  • An organic base employed in the above step comprises triethylamine, pyridine, sodium, sodium hydroxide, potassium hydroxide, etc., and preferably triethylamine.
  • an organic solvent employed in the above step comprises an inert solvent such as dichloromethane, tetrahydrofuran, ethyl acetate, acetonitrile, chloroform, ethyl ether and dioxane; and a polar solvent such as methanol, ethanol and propanol.
  • an inert solvent such as dichloromethane, tetrahydrofuran, ethyl acetate, acetonitrile, chloroform, ethyl ether and dioxane
  • a polar solvent such as methanol, ethanol and propanol.
  • it may be dioxane.
  • a dicarboxylic anhydride employed in the present invention comprises, but not limited to the following specific examples, dicarboxylic anhydride having 2 ⁇ 10 of carbon number, dicarboxylic anhydride having 2 ⁇ 10 of carbon number substituted by a lower alkyl group having 1 ⁇ 6 of carbon number.
  • it comprises succinic anhydride, maleinic anhydride, glutaric anhydride, 3-methylglutaric anhydride and 3,3-dimethylglutaric anhydride.
  • reaction may be preferably performed at a temperature of 0 ⁇ 50 °C , more preferably of 25 ° C , for one day.
  • An acid catalyst employed in the above step comprises sulfuric acid, hydrochloric acid, p-tohiene sulfonic acid, etc., and an organic solvent comprises may be toluene, benzene, etc.
  • the second method for preparing the present kojic acid derivatives may comprise the following steps.
  • dicarboxylic salt such as terephthalic salt, pyridinedicarboxylic salt and 2,4-hexadienedioic salt
  • reaction scheme 2 [Reaction Scheme 2] m $r°" ⁇ ⁇ admir. " " "
  • a chloride employed in the step (A) comprises thionyl chloride, oxalic chloride, phosphorus trichloride, phosphorus oxychloride, etc.
  • an organic solvent employed in the above step comprises chloroform, methylene chloride, tetrahydrofuran, dioxane, acetone, toluene, benzene, etc.
  • reaction may be preferably performed at a temperature of 0-80 ° C , more preferably of 10-40 ° C .
  • a hydroxide employed in said step (B) may be sodium hydroxide, potassium hydroxide, etc., and, an organic solvent may be ethanol, methanol, butanol, isopropyl alcohol, etc.
  • An organic solvent employed in said step (C) may be dimethyl formamide.
  • the kojic acid derivatives of the formula 1 obtained in the above methods may include, but not limited thereto, di(5-hydroxy-4-oxo(4H-pyran ⁇ 2-yl)methyl butan-l,4-dioate, di(5-hydroxy-4-oxo(4H-pyran-2-yl)methyl-2(E)-butan- 1 ,4-dioate, di(5-hydroxy-4-oxo(4H-pyran-2-yl)methyl pentan- 1 ,5-dioate, di(5-hydroxy-4-oxo(4H-pyran-2-yl)methyl 3-methylpentan- 1 ,5-dioate, di(5-hydroxy-4-oxo(4H-pyran-2-yl)methyl 3 ,3-dimethylpentan- 1 ,5-dioate, terephthalic acid bis(5-hydroxy-4-oxo-4H-pyran-2-ylmethyl) ester, isophthalic acid bis
  • Example 2 The same procedure as described in Example 1 was followed by employing kojyl 3,3-dimethylglutaric acid obtained in Reference Example 5 instead of kojyl succinic acid, to obtain 21.5g (yield : 75%) of the title compound as yellow solid.
  • melanin-inhibiting activity was measured by employing mouse's pigment cell.
  • Mel-Ab cell of C57BL/6 mouse was cultured in Dulbecco's modified Eagle's media (DMEM) in which 10%) of fetal bovine serum, lOOnM of 12-O-tetradecanoyl phorbol- 13 -acetate and InM of cholera toxin were added at a temperature of 37 ° C with 5% C0 2 .
  • DMEM Dulbecco's modified Eagle's media
  • the cultured Mel-Ab cell was detached with 0.25% of trypsin-EDTA, and then cultured in a concentration of 10 5 cells/well in 24-well plate.
  • the kojic acid derivatives of the present invention exhibit a strong activity of inhibiting melanin formation.
  • the kojic acid derivatives of the present invention exhibit a strong whitening effect.
  • the patch test was carried out by employing the conventional nutrition creams containing the compounds of Examples 1 ⁇ 10 in amount of 5 wt%.
  • the brachium of thirty (30) healthy volunteers (15 males and 15 females) was thoroughly washed with 70% of ethanol and applied with a finn chamber containing 20 ⁇ of a cream formulation containing 5 wt% of each of the compounds of Examples 1 ⁇ 10.
  • the finn chamber was thoroughly attached to the brachium using an adhesive tape for 24 hours.
  • a chamber containing only cream base was attached.
  • the adhesive tape and the finn chamber were removed, and the adherent site of the arm was wiped with a qauze to remove the remaining preparation and observed skin irritation, for example, erythma, edema, papule, etc. Another 24 hours later, the site was reexamined.
  • Table 3 The results are shown in Table 3. [Table 3]
  • the kojic acid derivatives of the present invention can exhibit a strong activity of inhibiting melanin formation and cure pigmentation of the skin, and therefore, can be incorporated as a whitening agent.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Cosmetics (AREA)
  • Pyrane Compounds (AREA)

Abstract

Cette invention concerne des nouveaux dérivés d'acide cojique représentée par la formule (I) suivante et leur mode de préparation. Dans cette formule, R est un groupe alkyle comptant de 2 à 10 atomes de carbone, substitué par un groupe alkyle inférieur à 1-6 atomes de carbone, ou non substitué ; un groupe alcényle comptant de 2 à 10 atomes de carbone : un groupe benzyle substitué ou non ; ou un groupe pyridine substitué ou non. Le dérivé d'acide cojique selon la formule (I), qui présente une forte activité d'inhibition de la formation de mélanine et de blocage de la pigmentation, est intégré à des produits cosmétiques de blanchiment de la peau.
PCT/KR2001/002298 2000-12-29 2001-12-28 Derive d'acide cojique et son mode de preparation WO2002053562A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR1020000085161A KR100365072B1 (ko) 2000-12-29 2000-12-29 신규 코지산 이합체 및 이의 제조방법
KR2000/85161 2000-12-29
KR10-2001-0076528A KR100436014B1 (ko) 2001-12-05 2001-12-05 신규 코지산 유도체 및 이의 제조방법
KR2001/76528 2001-12-05

Publications (1)

Publication Number Publication Date
WO2002053562A1 true WO2002053562A1 (fr) 2002-07-11

Family

ID=26638673

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2001/002298 WO2002053562A1 (fr) 2000-12-29 2001-12-28 Derive d'acide cojique et son mode de preparation

Country Status (1)

Country Link
WO (1) WO2002053562A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20160046136A (ko) 2014-10-20 2016-04-28 한밭대학교 산학협력단 신규한 코직산 컨쥬게이트 화합물 및 그의 용도
US20180116945A1 (en) * 2015-04-10 2018-05-03 Rutgers, The State University Of New Jersey Kojic Acid Polymers
CN112778439A (zh) * 2020-12-31 2021-05-11 青岛姿之妍化妆品科技有限责任公司 美白护肤品及其制备方法
WO2022171292A1 (fr) 2021-02-12 2022-08-18 Symrise Ag Médicament pour la prévention et le traitement de l'hyperpigmentation

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS60233071A (ja) * 1984-05-04 1985-11-19 Sansho Seiyaku Kk コウジ酸誘導体
EP0381057A2 (fr) * 1989-01-28 1990-08-08 Sansho Seiyaku Co., Ltd. Composition chimique pour application par voie externe
US4990330A (en) * 1987-09-25 1991-02-05 Sansho Seiyaku Co., Ltd. Compositions for topical use having melanin synthesis-inhibiting activity
US5486624A (en) * 1994-02-01 1996-01-23 Pacific Corporation Kojic acid derivative
US5523421A (en) * 1993-11-16 1996-06-04 Pacific Corporation Kojic acid derivatives
EP0819692A1 (fr) * 1996-07-18 1998-01-21 L'oreal Nouveau dérivé de l'acide kojique et son utilisation comme agent dépigmentant

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS60233071A (ja) * 1984-05-04 1985-11-19 Sansho Seiyaku Kk コウジ酸誘導体
US4990330A (en) * 1987-09-25 1991-02-05 Sansho Seiyaku Co., Ltd. Compositions for topical use having melanin synthesis-inhibiting activity
EP0381057A2 (fr) * 1989-01-28 1990-08-08 Sansho Seiyaku Co., Ltd. Composition chimique pour application par voie externe
US5523421A (en) * 1993-11-16 1996-06-04 Pacific Corporation Kojic acid derivatives
US5486624A (en) * 1994-02-01 1996-01-23 Pacific Corporation Kojic acid derivative
EP0819692A1 (fr) * 1996-07-18 1998-01-21 L'oreal Nouveau dérivé de l'acide kojique et son utilisation comme agent dépigmentant

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20160046136A (ko) 2014-10-20 2016-04-28 한밭대학교 산학협력단 신규한 코직산 컨쥬게이트 화합물 및 그의 용도
US20180116945A1 (en) * 2015-04-10 2018-05-03 Rutgers, The State University Of New Jersey Kojic Acid Polymers
JP2018513251A (ja) * 2015-04-10 2018-05-24 ラトガーズ， ザ ステイト ユニバーシティ オブ ニュー ジャージー コウジ酸ポリマー
US10543162B2 (en) * 2015-04-10 2020-01-28 Rutgers, The State University Of New Jersey Kojic acid polymers
CN112778439A (zh) * 2020-12-31 2021-05-11 青岛姿之妍化妆品科技有限责任公司 美白护肤品及其制备方法
WO2022171292A1 (fr) 2021-02-12 2022-08-18 Symrise Ag Médicament pour la prévention et le traitement de l'hyperpigmentation

Similar Documents

Publication Publication Date Title
EP2651886B1 (fr) Procédé de dépigmentation de matières kératiniques à l'aide de dérivés de résorcinol
EP1967175A1 (fr) Utilisation de dérivés de l'acide sinapinique et compositions comprenant de tels dérivés
EP2861555A1 (fr) Procédé de dépigmentation de matières kératiniques au moyen de nouveaux composés à base de résorcinol
CN110121491B (zh) 3,4,5-三甲氧基肉桂酸酯衍生物、其制备方法以及含有该衍生物的皮肤美白组合物
US20070258921A1 (en) Process for depigmenting the skin
CN108368026B (zh) 针对其化妆用途的间苯二酚衍生物
WO2002053562A1 (fr) Derive d'acide cojique et son mode de preparation
KR980009262A (ko) 코지산의 신규 유도체 및 탈색소제로서의 이의 용도
KR101219281B1 (ko) 젠티식산 유도체 화합물과 그 제조방법 및 이를 함유하는미백화장료 조성물
KR100957465B1 (ko) 히드록시신남산 유도체 화합물과 그 제조방법 및 이를함유하는 화장료 조성물
WO2018220020A2 (fr) Utilisation cosmétique de dérivés du résorcinol
KR100365072B1 (ko) 신규 코지산 이합체 및 이의 제조방법
KR100851044B1 (ko) 미백효과를 나타내는 3,5-디히드록시 벤즈아미드 유도체,및 이를 함유하는 화장료 조성물
CN111132965B (zh) 针对其美容用途的间苯二酚衍生物
KR100630905B1 (ko) 신규한 히드록시아닐린 유도체의 염을 포함하는 화장품조성물
WO2013190483A1 (fr) Nouveaux dérivés de résorcinol et utilisations cosmétiques de ceux-ci
KR20170011019A (ko) 아스코르빈산이 결합된 피리독신 유도체의 제조방법
KR100335340B1 (ko) 몰식자산 에스테르 화합물과 그 제조방법 및 이를 함유하는 미백화장료 조성물
KR100436014B1 (ko) 신규 코지산 유도체 및 이의 제조방법
KR20170076091A (ko) 살리실산 유도체와 그 제조방법 및 이를 함유하는 미백용 화장료 조성물
KR100706475B1 (ko) 신규 히드록시피라논 이합체, 그 염, 이들의 제조방법 및이들을 함유하는 피부 미백용 화장료 조성물
KR101457370B1 (ko) 신규 벤젠 디올 유도체 화합물 및 이를 이용한 화장료 조성물
KR100422762B1 (ko) 신규 코지산 유도체 및 이의 제조방법
KR100858523B1 (ko) 코지산 유도체와 그 제조방법, 및 이를 함유한 미백화장료 조성물
KR100630904B1 (ko) 신규한 히드록시아닐린 유도체의 염, 이의 제조 방법 및 이를 포함하는 화장품 조성물

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PH PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP