JPH01132586A - Riboflavin derivative - Google Patents
Riboflavin derivativeInfo
- Publication number
- JPH01132586A JPH01132586A JP29082287A JP29082287A JPH01132586A JP H01132586 A JPH01132586 A JP H01132586A JP 29082287 A JP29082287 A JP 29082287A JP 29082287 A JP29082287 A JP 29082287A JP H01132586 A JPH01132586 A JP H01132586A
- Authority
- JP
- Japan
- Prior art keywords
- vitamin
- acid
- red tide
- acid lactone
- lactone
- 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.)
- Pending
Links
- 150000003287 riboflavins Chemical class 0.000 title claims description 4
- 239000000126 substance Substances 0.000 claims description 2
- ZHEHPTDHYQQKJR-DRZSPHRISA-N (2s,3s,4s)-5-(7,8-dimethyl-2,4-dioxobenzo[g]pteridin-10-yl)-2,3,4-trihydroxypentanoic acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O ZHEHPTDHYQQKJR-DRZSPHRISA-N 0.000 abstract description 14
- -1 Vitamin B2 acid lactone Chemical class 0.000 abstract description 10
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 5
- 239000011541 reaction mixture Substances 0.000 abstract description 4
- 238000003756 stirring Methods 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract description 3
- 244000005700 microbiome Species 0.000 abstract description 3
- 150000002211 flavins Chemical class 0.000 abstract description 2
- 238000004237 preparative chromatography Methods 0.000 abstract description 2
- 235000001674 Agaricus brunnescens Nutrition 0.000 abstract 1
- 241001355965 Chattonella marina var. antiqua Species 0.000 abstract 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 abstract 1
- 238000006482 condensation reaction Methods 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- KPDQZGKJTJRBGU-UHFFFAOYSA-N lumiflavin Chemical compound CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O KPDQZGKJTJRBGU-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 241000180097 Chattonella Species 0.000 description 1
- 241001000743 Hibana Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 230000003779 hair growth Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- OOYGSFOGFJDDHP-KMCOLRRFSA-N kanamycin A sulfate Chemical group OS(O)(=O)=O.O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N OOYGSFOGFJDDHP-KMCOLRRFSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
産業上の利用分野
本発明は、生体内で加水分解されて種々の微生物（こ対
する生理活性、特に赤潮の本体をなすシャ育阻害活性を
有するビタミンＢ２酸となる新規なりポフラビン誘導体
に関する。DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention is a novel method for producing vitamin B2 acid, which is hydrolyzed in vivo and has physiological activity against various microorganisms, especially vitamin B2 acid, which has the activity of inhibiting hair growth, which is the main substance of red tide. This invention relates to poflavin derivatives.
従来の技術
るフラビン誘導体である次式（Ｉ’）：ＯＯＨ
−Ｃ−ＯＨ
−Ｃ−ＯＨ
−Ｃ−ＯＨ
ＨＯ
で表わされる７、８−ジメチル−１０−（２，３，４−
トリヒドロキシ−４−カルポキシブチルンイソアロキサ
ジン（以下、ビタミンＢ２酸という月ま、種々の微生物
で生理活性を示すだけでなく〔タチバナ（Ｓ、 Ｔａｃ
ｈｉｂａｎａ ）、ムラカミ（Ｉ、 Ｍｕｒａｋａｍｉ
）、モレキュラー・アンド・セルラー・バイオケミス
トリー（Ｍｏｌｅｃｕｌａｒ ａｎｄ Ｃｅ１ｌｕｌａ
ｒ Ｂｉｏｃｈｅｍ、 ）、第５１巻、第１４９頁（１
９８３年）〕、赤潮の本体をなすシャトネラ・アンチイ
カの生育を極めて低濃度（１■／ｌ）で著しく阻害する
ことが知られている〔古城、立花、醗酵工学、第６３巻
（第２号ン、第１３７頁（１９８５年）〕。A conventional flavin derivative, 7,8-dimethyl-10-(2,3,4-
Trihydroxy-4-carpoxybutyrinisoalloxazine (hereinafter referred to as vitamin B2 acid) not only shows physiological activity in various microorganisms [Tachibana (S, Tac)]
hibana), Murakami (I, Murakami
), Molecular and Cellular Biochemistry
r Biochem, ), Volume 51, Page 149 (1
983)] is known to significantly inhibit the growth of Chattonella antiica, which forms the main body of red tide, at extremely low concentrations (1■/l) [Koshiro, Tachibana, Fermentation Engineering, Vol. 63 (No. 2) N, p. 137 (1985)].
本発明は、このようなビタミンＢ２酸活性を有する新規
なリボフラビン誘導体を提供するためになされたもので
ある。The present invention was made to provide a novel riboflavin derivative having such vitamin B2 acid activity.
即ち本発明は、次式（１）： ％式％ で表わされるリボフラビン誘導体に関する。That is, the present invention provides the following formula (1): %formula% The present invention relates to a riboflavin derivative represented by:
式（Ｌ）で表わされる化合物（以下、ビタミンＢ２酸ラ
クトンという）の製造方法は特に限定的ではないが、好
適な方法はビタミンＢ２酸をエステル化剤、例えばＮ、
Ｎ’−ジシクロへキシルカルボジイミド等の脱水剤また
は濃硫酸、濃塩酸等の鉱酸、芳香族スルホン酸等の有機
酸等を用いて分子内エステル化させる方法である。The method for producing the compound represented by formula (L) (hereinafter referred to as vitamin B2 acid lactone) is not particularly limited, but a preferred method is to combine vitamin B2 acid with an esterifying agent such as N,
This is a method of intramolecular esterification using a dehydrating agent such as N'-dicyclohexylcarbodiimide, a mineral acid such as concentrated sulfuric acid or concentrated hydrochloric acid, or an organic acid such as aromatic sulfonic acid.
この場合、通常、ビタミンＢ２酸は０．１〜１００ｍｍ
ｏｌ／６のアルコール溶液として使用し、反応温度は室
温〜１２０℃とする。In this case, vitamin B2 acid is usually 0.1 to 100 mm
It is used as an ol/6 alcohol solution, and the reaction temperature is from room temperature to 120°C.
ビタミンＢ２酸ラクトンはビタミンＢ２酸に比べて、水
をこ対する溶解性はほとんど変らないが、脂溶性がやや
高く、特にアルコール等の有機溶剤に対する溶解性が高
い。Vitamin B2 acid lactone has almost the same solubility in water as vitamin B2 acid, but has slightly higher fat solubility, and particularly higher solubility in organic solvents such as alcohol.
以下、本発明を実施例によって説明する。Hereinafter, the present invention will be explained by examples.
実施例１
ビタミンＢ２酸１０．６ ｍｇ （２，６Ｘ １０−５
ｍｍｏｌ）、Ｎ。Example 1 Vitamin B2 acid 10.6 mg (2,6X 10-5
mmol), N.
Ｎ′−ジシクロへキシルカルボジイミド１２ｍｇ（５，
８Ｘ １０−５ｍｍｏｌ ）およびｎ−ブチルアルコー
ル５ｄを、撹拌器を備えた三つ口反応容器（３０ｍｌＪ
内に入れ、光を遮断した状態で、撹拌下、室温で１８時
間反応をおこなった。N'-dicyclohexylcarbodiimide 12 mg (5,
8X 10-5 mmol) and n-butyl alcohol 5d in a three-necked reaction vessel equipped with a stirrer (30mlJ
The reaction was carried out under stirring at room temperature for 18 hours while blocking light.
反応混合物を中圧分取りロマトグラフイー処理（ＯＤＳ
力７ム：１０φ×３００、移動相：ＣＨ３ＣＮ−Ｈ２ｏ
系月こ付すことによって、ビタミンＢ２酸ラクトンを６
．８ ｍｇ （１，８Ｘ １０−５ｍｍｏｌ ）得た（
収率６９．２％）。The reaction mixture was subjected to medium pressure preparative chromatography treatment (ODS
Force 7mm: 10φ×300, Mobile phase: CH3CN-H2o
By adding 60% of vitamin B2 acid lactone,
．． 8 mg (1,8X 10-5 mmol) was obtained (
yield 69.2%).
実施例２
ビタミンＢ２酸９．８ ｍｇ （２，４ｘ １０−５ｍ
ｍｏｌ ）、濃硫酸０．５ ｍＱおよびメチルアルコー
ル５ｍＱを、撹拌器を備えた三つ口反応容器（３０ｍｆ
ｆｉＪ内に入れ、光を遮断した状態で撹拌下、室温で反
応を２時間おこなった。Example 2 Vitamin B2 acid 9.8 mg (2.4x 10-5m
mol ), 0.5 mQ of concentrated sulfuric acid, and 5 mQ of methyl alcohol in a three-neck reaction vessel equipped with a stirrer (30 mF
The reaction was carried out at room temperature for 2 hours under stirring in a state where light was blocked.
反応混合物を実施例１と同様の処理に付すことによって
、ビタミンＢ２酸ラクトンを２．２ ｍｇ （５，９Ｘ
１０’ｍｍｏｌ ）得た（収率２４．６’！、）Ｃ，
この場合、ルミフラビンも３．８ ｍｇ （１，５Ｘ
１０−５ｍｍｏｌ ）得られた〕。By subjecting the reaction mixture to the same treatment as in Example 1, 2.2 mg of vitamin B2 acid lactone (5,9X
10'mmol) obtained (yield 24.6'!)C,
In this case, lumiflavin is also 3.8 mg (1,5X
10-5 mmol) obtained].
実施例３
撹拌器を備えた三つ口反応容器（５０ｍＱ）内にビタミ
ンＢ２酸２０．５ ｍｇ （５，ＯＸ １０−５ｍｍｏ
ｌ ） 、Ｎ、Ｎ’−ジシクロへ牛ジルカルボジイミド
１ ’５ ｍｇ （７，３ｘ１０−５ｍｍｏｌ ）およ
びｎ−ブチルアルコール２０ｍＱを入れ、湯浴上（５５
℃）において、光を遮断した状態で撹拌下で約１時間反
応をおこなった。Example 3 20.5 mg of vitamin B2 acid (5,OX 10-5 mmo
1), N,N'-dicyclo, 1'5 mg (7,3
The reaction was carried out for about 1 hour under stirring at a temperature of 10.degree. C. in the absence of light.
反応混合物を濃縮した後、冷暗所内に放置し、晶出した
ビタミンＢ２酸ラクトンを１４．５ ｍｇ （３，９ｘ
１０−５ｍｍｏｌ ）置数した（収率７８％）。After concentrating the reaction mixture, it was left in a cool and dark place, and 14.5 mg (3.9x
10-5 mmol) (yield 78%).
実施例４
光を遮断した状態で、反応容器内にビタミンＢ２酸１０
０ ｍｇ （２，４５Ｘ １０−’ｍｍｏｌ）を入れ、
定温恒温器内において５０〜１５０℃で数時間〜数十時
間加熱脱水をおこなった。反応は定量的に進行した。Example 4 Vitamin B2 acid 10 was placed in a reaction vessel with light blocked.
Add 0 mg (2,45X 10-'mmol),
Dehydration was performed by heating at 50 to 150° C. for several hours to several tens of hours in a constant temperature incubator. The reaction proceeded quantitatively.
生成物を再結晶処理に付してビタミンＢ２酸ラクトンを
６０ ｍｇ得た。The product was subjected to recrystallization treatment to obtain 60 mg of vitamin B2 acid lactone.
上記の実施例で得られたビタミンＢ２酸ラクトンのＵｖ
スペクトル、ＩＲスペクトル、’Ｈ−ＮＭＲスペクトル
および１３Ｃ−ＮＭＲスペクトルをそれぞれ第１図、第
２図、第３図および第４図に示す。Uv of vitamin B2 acid lactone obtained in the above example
The spectrum, IR spectrum, 'H-NMR spectrum and 13C-NMR spectrum are shown in FIGS. 1, 2, 3 and 4, respectively.
発明の効果
本発明によるビタミンＢ２酸ラクトンは加水分解をうけ
てビタミンＢ２酸活性を有するので、医薬品の分野等に
おいて有用なだけでなく、赤潮の防除剤としても利用可
能な化合物である。Effects of the Invention Since the vitamin B2 acid lactone according to the present invention has vitamin B2 acid activity after being hydrolyzed, it is a compound that is not only useful in the pharmaceutical field, but also can be used as a red tide control agent.
【図面の簡単な説明】
第１図、第２図、第３図および第４図はそれぞれビタミ
ンＢ２酸ラクトンのＵＶスペクトル、ＩＲスペクトル、
Ｈ−ＮＭＲスペクトルオヨヒ１３Ｃ−ＮＭＲスペクト
ルである。
狩野出願人 白水化学工栗株式会江
代 理 人 肯 １）保 ほか ２名[Brief explanation of the drawings] Figures 1, 2, 3 and 4 show the UV spectrum, IR spectrum, and IR spectrum of vitamin B2 acid lactone, respectively.
H-NMR spectrum Oyohi 13C-NMR spectrum. Kano applicant Hakusui Kagaku Kuri Co., Ltd. Osamu Eshiro Ken 1) Tamotsu and 2 others
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29082287A JPH01132586A (en) | 1987-11-17 | 1987-11-17 | Riboflavin derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29082287A JPH01132586A (en) | 1987-11-17 | 1987-11-17 | Riboflavin derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH01132586A true JPH01132586A (en) | 1989-05-25 |
Family
ID=17760930
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP29082287A Pending JPH01132586A (en) | 1987-11-17 | 1987-11-17 | Riboflavin derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01132586A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004013142A1 (en) * | 2002-08-02 | 2004-02-12 | The Institute Of Radiation Medicine, Academy Of Miilitary Medical Sciences, People's Liberation Army | A riboflavin derivative and its manufacture and uses |
| US7300372B2 (en) | 2002-07-16 | 2007-11-27 | Dayco Europe S.R.L. Con Unico Socio | Integrated pulley-torsional damper assembly |
-
1987
- 1987-11-17 JP JP29082287A patent/JPH01132586A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7300372B2 (en) | 2002-07-16 | 2007-11-27 | Dayco Europe S.R.L. Con Unico Socio | Integrated pulley-torsional damper assembly |
| WO2004013142A1 (en) * | 2002-08-02 | 2004-02-12 | The Institute Of Radiation Medicine, Academy Of Miilitary Medical Sciences, People's Liberation Army | A riboflavin derivative and its manufacture and uses |
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