JPH045299A - Tocopheryl alpha-d-glucoside and derivative thereof - Google Patents
Tocopheryl alpha-d-glucoside and derivative thereofInfo
- Publication number
- JPH045299A JPH045299A JP10830790A JP10830790A JPH045299A JP H045299 A JPH045299 A JP H045299A JP 10830790 A JP10830790 A JP 10830790A JP 10830790 A JP10830790 A JP 10830790A JP H045299 A JPH045299 A JP H045299A
- Authority
- JP
- Japan
- Prior art keywords
- tocopheryl
- sugar
- alpha
- glucoside
- group
- 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
- -1 Tocopheryl alpha-d-glucoside Chemical class 0.000 title claims description 11
- ZAKOWWREFLAJOT-ADUHFSDSSA-N [2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-yl] acetate Chemical group CC(=O)OC1=C(C)C(C)=C2OC(CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-ADUHFSDSSA-N 0.000 claims abstract description 13
- 125000002252 acyl group Chemical group 0.000 claims abstract description 3
- 239000000126 substance Substances 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 23
- 239000011732 tocopherol Substances 0.000 abstract description 10
- 229930003799 tocopherol Natural products 0.000 abstract description 10
- 230000003266 anti-allergic effect Effects 0.000 abstract description 4
- 230000001766 physiological effect Effects 0.000 abstract description 4
- 235000019149 tocopherols Nutrition 0.000 abstract description 4
- QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 abstract description 4
- 239000003880 polar aprotic solvent Substances 0.000 abstract description 2
- OPHAQGBSVLXVOL-GGZOMVNGSA-N 1-[(2r,3r,4r)-4,6-diacetyl-3,4-dihydroxy-2-(hydroxymethyl)-2,3-dihydropyran-5-yl]ethanone Chemical compound CC(=O)C1=C(C(C)=O)[C@](O)(C(C)=O)[C@H](O)[C@@H](CO)O1 OPHAQGBSVLXVOL-GGZOMVNGSA-N 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- PNDVLJQMORRYJM-UHFFFAOYSA-M sodium;acetic acid;nitrite Chemical compound [Na+].ON=O.CC([O-])=O PNDVLJQMORRYJM-UHFFFAOYSA-M 0.000 abstract 1
- 235000000346 sugar Nutrition 0.000 description 25
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 229960001295 tocopherol Drugs 0.000 description 6
- 235000010384 tocopherol Nutrition 0.000 description 6
- 229930182470 glycoside Natural products 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 230000000704 physical effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000010446 mirabilite Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 150000008151 D-glucosides Chemical class 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000005646 oximino group Chemical group 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 150000003611 tocopherol derivatives Chemical class 0.000 description 1
- 150000008494 α-glucosides Chemical class 0.000 description 1
- 150000008135 α-glycosides Chemical class 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
- 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、生理活性上Ｈ用な、とりわけ、抗アレルギー
活性を膏ずろ新規なトコフェリル α−Ｄ−グリコシド
及びその誘導体に関する。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to novel tocopheryl α-D-glycosides and derivatives thereof that exhibit physiological activity, particularly antiallergic activity.
周知のように、トコフェロールの配糖体は抗アレルギー
活性を有し、とりわけヒスタミン遊離抑制作用が大きい
化合物である。このようなトコフェロール類と糖類の配
糖体が抗アレルギー活性を示す記載は、特開昭６１−１
３０２２９号公報、特開昭６１−３０５９４号公報等に
記載されている。As is well known, tocopherol glycosides have antiallergic activity, and are compounds that have a particularly strong effect on suppressing histamine release. The description that glycosides of tocopherols and sugars exhibit antiallergic activity is disclosed in JP-A-61-1.
It is described in JP-A-30229, JP-A-61-30594, and the like.
ところで、トコフェロールの配糖体のうち、糖の成分が
グルコースより成る化合物に関しては、トコフェロール
のグルコースに対する結合様式に２１１ｆｌ（α体、β
体）あり、このうちβ体（トコフェリルβ−ゲルコンド
）は、特開昭６０−５６９９４号公報、特開昭６１−３
０５９４号公報に記載されているように公知である。By the way, among tocopherol glycosides, for compounds whose sugar component is glucose, the binding mode of tocopherol to glucose is 211fl (α form, β form).
Among them, the β-form (tocopheryl β-gelcondo) is disclosed in JP-A-60-56994 and JP-A-61-3.
This method is known as described in Japanese Patent No. 0594.
一方、α体（トコフェリル α−Ｄ−グルフンド）につ
いては何の情報しなく、その詳細な物性については全く
不明であった。On the other hand, no information was available about the α-isomer (tocopheryl α-D-glufund), and its detailed physical properties were completely unknown.
本発明は、従来技術とは異なる新規のトコフェリルα−
Ｄ−グルコシド及びその誘導体に関し、その構造を正確
にとらえ、かつ、生理活性の優れたトコフェロールの配
糖体を提供することにある。The present invention provides novel tocopheryl α-
Regarding D-glucoside and its derivatives, the present invention aims to provide a tocopherol glycoside whose structure is accurately determined and which has excellent physiological activity.
本発明は、前記従来の課題に鑑みてなされてもので、そ
の課題は、新規のトコフェリル α−Ｄ−ゲルコンドお
よびその誘導体を提供することにある。The present invention has been made in view of the above-mentioned conventional problems, and its object is to provide a novel tocopheryl α-D-gelcond and its derivatives.
即ち、本願の第１の発明は、−船蔵 ［１）（式ｌ中、
Ｒ１は水素原子またはアンル基を表し、Ｒ２はトフフェ
リル基を表す）で示される化合物である。That is, the first invention of the present application is - Funagura [1) (in formula l,
R1 represents a hydrogen atom or anru group, and R2 represents a topheryl group).
この式１で表される化合物の例としては次に挙げろ化合
物がある。Examples of the compound represented by Formula 1 include the following compounds.
１、ｄｌ −α−トコフェリル α−Ｄ−グルコピラ
ノンド
２、ｄｌ−α−トコフエリル ２．３．４．６−チトラ
アセチルーα−Ｄ−グルコピラノシド３、ｄｌ −α−
トコフェリル ３．４．６−トリアセチル−α−Ｄ−グ
ルフビラノノド
その他、アグリコンとしてβ−トコフエリル、ζ−トコ
フエリル、ε−トコフエリル、η−トコフェリル 等を
導入した化合物も１〜３同様に得ることができる。1, dl -α-tocopheryl α-D-glucopyranoside 2, dl-α-tocopheryl 2.3.4.6-Titraacetyl-α-D-glucopyranoside 3, dl -α-
Tocopheryl 3.4.6-Triacetyl-α-D-glufubiranonod and other compounds into which β-tocopheryl, ζ-tocopheryl, ε-tocopheryl, η-tocopheryl, etc. are introduced can also be obtained in the same manner as in 1 to 3.
また、本願の第２の発明は、−船蔵 ＣＨＩ）（式■中
、Ｒ２はトコフエリル基を表し、Ｒ３は水素原子または
アセトキノ基を表す）で表される化合物である。Moreover, the second invention of the present application is a compound represented by -Funazura CHI) (in formula (1), R2 represents a tocopheryl group, and R3 represents a hydrogen atom or an acetoquino group).
この式ｎで示されろ化合物は、−船蔵［１］で示される
化合物を製造する際の合成中間体として有用な化合物で
ある。The compound represented by this formula n is a compound useful as a synthetic intermediate in producing the compound represented by -Funazura [1].
次に、これらの化合物の製造法について述べる。Next, methods for producing these compounds will be described.
本発明者らは種々検討の結果、従来技術による各種の酸
触媒を用いたトコフェロール配糖体の製造方法では、目
的とするトコフェリルーα−Ｄ−グルフシドを選択的に
得る事は不可能であることを確認した。As a result of various studies, the present inventors have found that it is impossible to selectively obtain the target tocopherol α-D-glufuside using conventional methods for producing tocopherol glycosides using various acid catalysts. It was confirmed.
そこで、本発明者らが先に発明した、２−アミノ糖類を
糖残基とするトコフェロール誘導体に関する先の出願（
特願平１−１１９２９０号）に記載された、トリアセチ
ルグルカールよりグイメリック ３．４．６−トリー〇
−アセチルー２−デオキン−２−ニトロソ−α−Ｄ−グ
ルコピラノンルクロライドを合成し、この化合物とトコ
フェロール類とを極性非プロトン溶媒中反応させること
により収率良くトコフエリル ３．４．６−）ソー０ア
セチルー２−オキンミノーα−Ｄ−アラビノへキノピラ
ノシドを得た。Therefore, the present inventors' earlier application regarding tocopherol derivatives having 2-amino sugar as the sugar residue (
Synthesize Gwymeric 3.4.6-tri〇-acetyl-2-deokyne-2-nitroso-α-D-glucopyranone luchloride from triacetyl glucar as described in Japanese Patent Application No. 1-119290). By reacting this compound with tocopherols in a polar aprotic solvent, tocopheryl 3.4.6-)so-0-acetyl-2-okhimino α-D-arabinoquinopyranoside was obtained in good yield.
次に、ここで得られた化合物を酢酸中、亜硝酸ソーダと
反応させてオキシミノ基をケトンに変換した後還元する
ことによってα−Ｄ−ゲルコンド骨格に導いた。この段
階で精製すると目的とするトコフェリル α−Ｄ−グル
コシドを得ることができ、またこれをアシル化するとア
シル誘導体を得ることができる。Next, the compound obtained here was reacted with sodium nitrite in acetic acid to convert the oximino group into a ketone, and then reduced to form an α-D-gelcondo skeleton. Purification at this stage can yield the desired tocopheryl α-D-glucoside, and acylation of this can yield acyl derivatives.
更に、このトコフエリル α−Ｄ−ゲルコツトは３．４
．６− トリー〇−アセチルー１．２−エポキシグルコ
ースとトコフェロール類との炭化水素系溶媒中反応させ
ることからら容易にトコフエリル３．４゜６−トリー〇
−アセチルーα−Ｄ−グルコシドを得ることができ、こ
れは常法によりアンモニア飽和メタノールやメタノール
中ナトリウムメトキシドの存在下で脱アセチルすること
ができる。Furthermore, this tocopheryl α-D-gelkoto is 3.4
．． Tocopheryl 3.4° 6-tri〇-acetyl-α-D-glucoside can be easily obtained by reacting 6-tri〇-acetyl-1,2-epoxyglucose and tocopherols in a hydrocarbon solvent. , which can be deacetylated by conventional methods in the presence of ammonia-saturated methanol or sodium methoxide in methanol.
また、このエポキシドを用いる合成法は３．４．６位の
水酸基はアセチルにて保護され、２位水酸基のみアセチ
ル化されない特異的な水酸基の保護状態の化合物も得る
ことができる。In addition, the synthesis method using this epoxide can also yield a compound in which the hydroxyl groups at positions 3, 4, and 6 are protected with acetyl, and the hydroxyl group at position 2 is not acetylated in a specific hydroxyl group protected state.
この様にして得られる化合物がα体（α配糖体）である
ことは核磁気共鳴スペクトルによる糖Ｃ１位〜０２位の
環プロトンの結合定数から明らかにすることができる。The fact that the compound obtained in this manner is an α-form (α-glycoside) can be determined from the coupling constants of the ring protons at positions C1 to C02 of the sugar determined by nuclear magnetic resonance spectroscopy.
即ち、１位、２位のプロトンがシス配置（α体）のとき
は、結合定数が５〜６Ｈｚ以下となり、トランス配置（
β体）のときは５〜６Ｈｚ以上となる。本発明の例は３
．６Ｈｚであることからα体であることが明らかとなり
、更に比旋光度も、ｄｌ−α−トコフエリル ２．３．
４ 。That is, when the protons at the 1st and 2nd positions are in the cis configuration (α form), the coupling constant is 5 to 6 Hz or less, and the trans configuration (
β-form), the frequency is 5 to 6 Hz or higher. Examples of the present invention are 3
．． 6 Hz, it is clear that it is the α-isomer, and the specific rotation is also dl-α-tocopheryl 2.3.
4.
６−チトラーＯ−アセチルーα−Ｄ−ゲルコツトでは〔
α）Ｄ＝＋４６．９° （ｃ＝１．０／クロロホルム）
、〔α）Ｄ ＝＋６０．３° （Ｃ＝１０／メタノー
ル）であるのに対し、ｄｉ −α−トコフエリル ２．
３．４．６−テトラ−０−アセチルーβ−Ｄ−グルコシ
ドでは、本発明者らのデータでは〔α）Ｄ＝−１０，３
° （Ｃ＝１．３／クロロホルム）、〔α）Ｄ＝−４，
２° （Ｃ＝１．０／メタノール）であった。このこと
からも、本発明の化合物群は、αグルコシド誘導体であ
ることが分かる。In 6-Chitler O-acetyl-α-D-Gerkost [
α) D=+46.9° (c=1.0/chloroform)
, [α)D = +60.3° (C = 10/methanol), whereas di -α-tocopheryl 2.
3.4.6-Tetra-0-acetyl-β-D-glucoside, according to our data [α)D=-10,3
° (C=1.3/chloroform), [α)D=-4,
2° (C=1.0/methanol). This also shows that the compound group of the present invention is an α-glucoside derivative.
以下に実施例により本発明を更に詳しく説明するが、こ
れらの実施例によって本発明を同等制限するものではな
い。EXAMPLES The present invention will be explained in more detail with reference to Examples below, but the present invention is not limited to the same extent by these Examples.
（実施例１）
１．２−エポキシ−３，５，６−トリー〇−アセチルー
Ｄ−グルコース２．０ｇをトルエン３０１に溶解させ窒
素気流下、ｄｉ −α−トコフェロール２．９８ｇを添
加し、２０時間加熱還流させた。(Example 1) 2.0 g of 1.2-epoxy-3,5,6-tri-acetyl-D-glucose was dissolved in 301 toluene, and 2.98 g of di-α-tocopherol was added under a nitrogen stream. The mixture was heated to reflux for an hour.
その後、減圧下にトルエンを留去し、残渣をカラムクロ
マトグラフィー法（シリカゲル、ヘキサン、酢酸エチル
）によって精製し、油状の目的物１．５ｇを得た。Thereafter, toluene was distilled off under reduced pressure, and the residue was purified by column chromatography (silica gel, hexane, ethyl acetate) to obtain 1.5 g of the target product as an oil.
４００ＭＨｚプロトン核磁気共鳴スペクトル（ＣＤ Ｃ
ｌ ｓ、δ値）
０．８３〜０．９ １５８
１．０〜１．９ ２５Ｈ
２，０〜２．４ １８Ｈ
２，４７２位水酸基水素
２．５６ ２８
３．８９ 糖Ｃ２位 ＩＨ（−）
４．０９ 糖Ｃ６位 ＩＨ（ｄｄ、Ｊ＝１２．４Ｈｚ、
Ｊ＝２Ｈｚ）
４．２７ 糖Ｃ６位 ＩＨ（ｄｄ、Ｊ＝１２．４Ｈｚ
、Ｊ＝５．２Ｈｚ ）
４．４５ 糖０５位 ＩＨ（ｍ）
５．０９ 糖０４位 ＩＨ（ｔ 、Ｊ＝９．６Ｈｚ）５
．３２ 糖Ｃｔ位 ＩＨ（ｄ 、Ｊ＝３．６Ｈｚ）５４
５ 糖０３位 ＩＨ（ｔ 、Ｊ＝９．６Ｈｚ）（尚、−
はマルチプレット、ｄｄはダブルダブレット、【はトリ
プレット、ｄはダブレットの意味である。以下の実施例
も同じ）
（実施例２）
含」（
実施例１で得られた化合物の０．５ｇを５ｍｌの乾燥ピ
リジンに溶解後、５１１１の無水酢酸をここに添加し２
０時間室温で撹拌させた。その後、減圧下にて濃縮しカ
ラムクロマトグラフィー法（シリカゲル、ヘキサン、酢
酸エチル）にて精製し油状の目的物０．４３ｇを得た。400MHz proton nuclear magnetic resonance spectrum (CDC
l s, δ value) 0.83-0.9 158 1.0-1.9 25H 2,0-2.4 18H 2,472-position hydroxyl hydrogen 2.56 28 3.89 Sugar C2-position IH (-) 4.09 Sugar C6 position IH (dd, J=12.4Hz,
J=2Hz) 4.27 Sugar C6 position IH (dd, J=12.4Hz)
, J=5.2Hz) 4.45 Sugar 05th position IH (m) 5.09 Sugar 04th position IH (t, J=9.6Hz)5
．． 32 Sugar Ct position IH (d, J=3.6Hz) 54
5 Sugar 03 position IH (t, J=9.6Hz) (in addition, -
is a multiplet, dd is a double-doublet, [ is a triplet, and d is a doublet. (The same applies to the following examples) (Example 2) (Example 2) After dissolving 0.5 g of the compound obtained in Example 1 in 5 ml of dry pyridine, 5111 acetic anhydride was added thereto.
Allow to stir at room temperature for 0 hours. Thereafter, it was concentrated under reduced pressure and purified by column chromatography (silica gel, hexane, ethyl acetate) to obtain 0.43 g of the target product as an oil.
比旋光度［α］Ｄ＝＋４６．９° （Ｃ＝１．０゜ＣＨ
Ｃｌ１．２９℃）４００ＭＨｚプロトン核磁気共鳴スペ
クトル（ＣＤ Ｃｌ ｓ、δ値）０．８４〜０．８８
１５Ｈ
１，０〜１．５６ ２３Ｈ
１ 、７９
１９〜２ 、２５
２ 、５５
４ 、 １４
４ 、５３
５ 、０９
糖０６位ＩＨ
糖０６位ＩＨ
糖Ｃ５位ＩＨ
糖０２位ＩＨ
５２６糖Ｃ１位１
５．８０ 糖Ｃ３位１
赤外線吸収スペクトル
（ｃ−−’）
（実施例３）
７５５．１４６０．１３７０．１２３０゜ Ｈ
１Ｈ
２Ｈ（ｔ 、Ｊ＝６． ４
Ｈｚ）
（ｄｄ、Ｊ＝１２． ８Ｈｚ
Ｊ＝４．４Ｈｚ）
（霞 ）
（ｄｄ、Ｊ＝１０Ｈｚ。Specific optical rotation [α]D=+46.9° (C=1.0°CH
Cl1.29℃) 400MHz proton nuclear magnetic resonance spectrum (CD Cl s, δ value) 0.84-0.88
15H 1,0-1.56 23H 1 ,79 19-2 ,25 2 ,55 4 ,14 4 ,53 5 ,09 Sugar 06 position IH Sugar 06 position IH Sugar C5 position IH Sugar 02 position IH 526 Sugar C1 position 1 5.80 Sugar C3 position 1 Infrared absorption spectrum (c--') (Example 3) 755.1460.1370.1230° H 1H 2H (t, J = 6.4 Hz) (dd, J = 12.8 Hz J=4.4Hz) (Kasumi) (dd, J=10Hz.
Ｊ＝３． ６Ｈｚ）
Ｈ（ｄ 、Ｊ＝３． ６Ｈｚ）
Ｈ（ｔ 、Ｊ＝ｌ ０Ｈ２）
（ＫＢｒ）（主要吸収値）
上記特願平１−１１９２９０号に記載の方法にしたがっ
て、ｄｉ−α−トコフエリル ３．４．６＝トリー〇−
アセチル−２−オキシミノ−α−Ｄアラビノへキノビラ
ノンドを５．０ｇ合成した。J=3. 6Hz) H(d, J=3.6Hz) H(t, J=l 0H2) (KBr) (principal absorption value) di-α-tocopheryl 3 .4.6=Tory〇-
5.0 g of quinobiranond to acetyl-2-oximino-α-D arabino was synthesized.
これを酢酸１００１に溶解させ、ここに亜硝酸ソーダ飽
和水溶液５０−１を室温で、ゆっくり滴下し、５時間撹
拌後多量の塩化メチレンを加えた。これを炭酸ソーダ水
溶液で洗浄し、更に飽和食塩水溶液にて洗浄した。塩化
メチレン層は芒硝で脱水後濃縮し、油状の残渣４．６ｇ
を得た。このものは薄層クロマトグラフィー法による分
析でも分解するので、これ以上の精製は行わなかった。This was dissolved in acetic acid 1001, a saturated aqueous solution of sodium nitrite 50-1 was slowly added dropwise thereto at room temperature, and after stirring for 5 hours, a large amount of methylene chloride was added. This was washed with an aqueous sodium carbonate solution and further washed with a saturated saline solution. The methylene chloride layer was dehydrated with Glauber's salt and concentrated, leaving 4.6 g of oily residue.
I got it. Since this product was decomposed even when analyzed by thin layer chromatography, no further purification was performed.
しかし、核磁気共鳴スペクトルできわめて純度よく目的
化合物に変換されていることが判明した。However, nuclear magnetic resonance spectroscopy revealed that it was converted to the target compound with extremely high purity.
比旋光度〔α）Ｄ ＝＋３７．５° （Ｃ＝１．０／
クロロホルム、２８℃）４００ＭＨｚプロトン核磁気共
鳴スペクトル（δ値、ＣＤ ０１ ｓ）０８３〜０．８
８ １５Ｈ
１，０〜１．９ ２５Ｈ
２，０〜２．２５ １８Ｈ
２、５７２８（ｔ 、Ｊ＝６． ８Ｈｚ）４．２６
１８ 糖０６位（ｄｄ、Ｊ＝２．４Ｈｚ。Specific optical rotation [α) D = +37.5° (C = 1.0/
Chloroform, 28°C) 400MHz proton nuclear magnetic resonance spectrum (δ value, CD 01 s) 083-0.8
8 15H 1,0-1.9 25H 2,0-2.25 18H 2,5728 (t, J=6.8Hz) 4.26
18 Sugar 06 position (dd, J=2.4Hz.
Ｊ＝１２．４Ｈｚ） ４．４０ １８ 糖０６位（ｄｄ、Ｊ＝４．８Ｈｚ。J=12.4Hz) 4.40 18 Sugar 06 position (dd, J=4.8Hz.
Ｊ＝１２．４Ｈｚ）
４．８９ １Ｈ糖Ｃ５位（＋ ）
４．９５ １８ 糖ＣＩ位（８）
５．４３ １Ｈ糖Ｃ４位（ｔ、Ｊ＝Ｉ Ｏ，４Ｈｚ）５
．９７ １８ ８０３位（ｄ、Ｊ＝ＩＯ，４Ｈｚ）（但
し、Ｓはシングレットを意味する）（実施例４）
含」（
実施例３で得られた化合物０．５ｇを８ｍｌの１゜４−
ジオキサンに溶解させ、ここに水を１ｍｌ添加した後、
水素化はう素ナトリウム４０−ｇを徐々に添加した。室
温で一晩撹拌後、希塩酸で弱酸性とした後クロロホルム
で抽出し、水洗、脱水後ピリジン中無水酢酸でアセチル
化し、常法により後処理を行って油状物０．４２ｇを得
た。この油状物は核磁気共鳴スペクトルによる分析で、
糖０２位の環プロトンのケミカルシフト値が５．０９ｐ
ｐ自で１ＯＨｚと３．６Ｈｚのダブルダブレットになっ
ていた。更にその他のケミカルシフト値も実施例２の結
果と全く一致した。そして、その他の不純物ピークが見
られなかったことから、糖骨格２位のアセトキン基はエ
カトリアル（赤道）配置をしたグルコース型となってい
る化合物のみが生成したと判断できた。J=12.4Hz) 4.89 1H sugar C5 position (+) 4.95 18 Sugar CI position (8) 5.43 1H sugar C4 position (t, J=I O, 4Hz) 5
．． 97 18 803rd position (d, J=IO, 4Hz) (S means singlet) (Example 4)
After dissolving in dioxane and adding 1 ml of water,
40-g of sodium borohydride was slowly added. After stirring overnight at room temperature, the mixture was made weakly acidic with diluted hydrochloric acid, extracted with chloroform, washed with water, dehydrated, acetylated with acetic anhydride in pyridine, and worked up in a conventional manner to obtain 0.42 g of an oil. This oily substance was analyzed by nuclear magnetic resonance spectroscopy.
The chemical shift value of the ring proton at sugar 02 position is 5.09p
It was a doublet of 1OHZ and 3.6Hz on the p own. Furthermore, other chemical shift values were completely consistent with the results of Example 2. Since no other impurity peaks were observed, it was determined that only a compound in which the acetoquine group at the 2-position of the sugar skeleton was in the equatorial (equatorial) configuration was produced.
（実施例５）
ｄｉ −α−トコフェリル α−Ｄ−グルコピラノシド
の合成
実施例４で得られた化合物０．３ｇを５０１のアンモニ
ア飽和メタノールに溶解させ、５時間室温にて撹拌させ
た。溶媒を減圧下に留去後クロロホルムに溶解させ、こ
れを水洗し、芒硝で脱水後油状物０．２２ｇを得た。カ
ラムクロマトグラフィ（シリカゲル、クロロホルム、メ
タノール）により精製し０．２ｇの油状物を得た。(Example 5) Synthesis of di-α-tocopheryl α-D-glucopyranoside 0.3 g of the compound obtained in Example 4 was dissolved in 501 ammonia-saturated methanol and stirred at room temperature for 5 hours. After distilling off the solvent under reduced pressure, the residue was dissolved in chloroform, washed with water, and dehydrated with Glauber's salt to obtain 0.22 g of an oily substance. Purification by column chromatography (silica gel, chloroform, methanol) gave 0.2 g of an oil.
比旋光度〔α〕Ｄ ＝＋７７．９° （Ｃ＝ ０ 。Specific optical rotation [α]D = +77.9° (C = 0.
７２．クロロホルム、２７℃）赤外線吸収スペクトル（
ＫＢｒ）（主要吸収値）（ｃ釦−′）３３７５．２９５
０．１４６０．１３８０．１２５００２Ｏ４００プロト
ン核磁気共鳴スペクトル（δ値、ＣＤＣｌ５）
０．８〜０．９ １５８
１．０〜１．９ ２３８
２．０４ ３８
２．２３ − ３８
２．２６ ３８
２．５７ ２Ｈ
３，４４糖Ｃ４位ＩＨ（ｔ）
３．５６ 糖Ｃ２位ＩＨ（ｄｄ 、Ｊ＝ＩＯ，４Ｈｚ。72. Chloroform, 27℃) infrared absorption spectrum (
KBr) (main absorption value) (c button-') 3375.295
0.1460.1380.125002O400 Proton nuclear magnetic resonance spectrum (δ value, CDCl5) 0.8-0.9 158 1.0-1.9 238 2.04 38 2.23 - 38 2.26 38 2.57 2H 3,44 Sugar C4 position IH (t) 3.56 Sugar C2 position IH (dd, J=IO, 4Hz.
Ｊ＝４．０Ｈｚ）
３．６５〜３．８ 糖Ｃ６位２Ｈ（＠）３．８８ 糖０
３位ＩＨ（ｔ 、Ｊ＝１０．４Ｈｚ）４．０２〜４．０
９ 糖０５位ＩＨ（ｍ）５．１８ 糖Ｃｔ位Ｉ Ｈ（ｄ
、Ｊ＝４．０Ｈ２）〔発明の効果〕
以上説明したように、本発明のトコフェロール誘導体は
、新規のトコフェロールのα配糖体群であり、従来のト
コフェロール類の配糖体の製造に於いては工業的に製造
はきわめて困難であり、従ってその重要な物性値も全く
不明であった。今回ここにその物性値の主要部分を明ら
かにし、生理活性上重要な化合物を提供することができ
た。J=4.0Hz) 3.65-3.8 Sugar C6 position 2H (@) 3.88 Sugar 0
3rd place IH (t, J=10.4Hz) 4.02-4.0
9 Sugar 05 position IH (m) 5.18 Sugar Ct position IH (d
. It is extremely difficult to manufacture industrially, and therefore its important physical properties are completely unknown. This time, we were able to clarify the main part of its physical properties and provide a compound that is important in terms of physiological activity.
Claims (1)
２はトコフェリル基を表す）で示されるトコフエリルα
−Ｄ−グルコシド及びその誘導体。 ２、上記Ｒ１が水素原子またはアセチル基であり、Ｒ２
がｄｌ−α−トコフェリル基である請求項１に記載のト
コフェリルα−Ｄ−グルコシド及びその誘導体。 ３、一般式〔II〕 ▲数式、化学式、表等があります▼（II） （式II中、Ｒ２は、トコフェリル基を表しＲ３は水酸基
またはアセトキシ基を表す）で示されるトコフェリルα
−Ｄ−グルコシド及びその誘導体。 ４、一般式〔II〕においてＲ２がｄｌ−α −トコフェリル基である請求項３に記載のトコフェリル
α−Ｄ−グルコシド及びその誘導体。[Claims] 1. General formula [I] ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (I) (In formula I, R1 represents a hydrogen atom or an acyl group, and R
2 represents a tocopheryl group) tocopheryl α
-D-glucoside and its derivatives. 2. The above R1 is a hydrogen atom or an acetyl group, and R2
Tocopheryl α-D-glucoside and its derivatives according to claim 1, wherein is dl-α-tocopheryl group. 3. General formula [II] ▲ Numerical formula, chemical formula, table, etc. ▼ (II) (In formula II, R2 represents a tocopheryl group and R3 represents a hydroxyl group or an acetoxy group) Tocopheryl α
-D-glucoside and its derivatives. 4. Tocopheryl α-D-glucoside and its derivatives according to claim 3, wherein R2 in the general formula [II] is a dl-α-tocopheryl group.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10830790A JPH045299A (en) | 1990-04-24 | 1990-04-24 | Tocopheryl alpha-d-glucoside and derivative thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10830790A JPH045299A (en) | 1990-04-24 | 1990-04-24 | Tocopheryl alpha-d-glucoside and derivative thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH045299A true JPH045299A (en) | 1992-01-09 |
Family
ID=14481388
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10830790A Pending JPH045299A (en) | 1990-04-24 | 1990-04-24 | Tocopheryl alpha-d-glucoside and derivative thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH045299A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4947437A (en) * | 1989-08-30 | 1990-08-07 | Firebaugh William H | Stereo microphone |
-
1990
- 1990-04-24 JP JP10830790A patent/JPH045299A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4947437A (en) * | 1989-08-30 | 1990-08-07 | Firebaugh William H | Stereo microphone |
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