JPH0536441B2 - - Google Patents
Info
- Publication number
- JPH0536441B2 JPH0536441B2 JP15882383A JP15882383A JPH0536441B2 JP H0536441 B2 JPH0536441 B2 JP H0536441B2 JP 15882383 A JP15882383 A JP 15882383A JP 15882383 A JP15882383 A JP 15882383A JP H0536441 B2 JPH0536441 B2 JP H0536441B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- added
- toluene
- dissolved
- under reduced
- 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.)
- Expired - Lifetime
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 150000004676 glycans Chemical class 0.000 claims description 5
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 claims description 5
- 229920001282 polysaccharide Polymers 0.000 claims description 4
- 239000005017 polysaccharide Substances 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 87
- 150000001875 compounds Chemical class 0.000 description 85
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 81
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 29
- 239000000203 mixture Substances 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
- 239000000243 solution Substances 0.000 description 19
- 239000002904 solvent Substances 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- 238000001914 filtration Methods 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- -1 acetyl compound Chemical class 0.000 description 10
- 150000004043 trisaccharides Chemical class 0.000 description 10
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- 239000012141 concentrate Substances 0.000 description 5
- 235000008504 concentrate Nutrition 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 4
- 238000003381 deacetylation reaction Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- 101150003085 Pdcl gene Proteins 0.000 description 3
- 229910004298 SiO 2 Inorganic materials 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000006196 deacetylation Effects 0.000 description 3
- 238000006264 debenzylation reaction Methods 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 239000002808 molecular sieve Substances 0.000 description 3
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 2
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 2
- BLAKAEFIFWAFGH-UHFFFAOYSA-N acetyl acetate;pyridine Chemical compound C1=CC=NC=C1.CC(=O)OC(C)=O BLAKAEFIFWAFGH-UHFFFAOYSA-N 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 150000002016 disaccharides Chemical class 0.000 description 2
- 238000002523 gelfiltration Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 1
- RNHDAKUGFHSZEV-UHFFFAOYSA-N 1,4-dioxane;hydrate Chemical compound O.C1COCCO1 RNHDAKUGFHSZEV-UHFFFAOYSA-N 0.000 description 1
- SKDHHIUENRGTHK-UHFFFAOYSA-N 4-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=C(C(Cl)=O)C=C1 SKDHHIUENRGTHK-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- 229930182474 N-glycoside Natural products 0.000 description 1
- 229910002666 PdCl2 Inorganic materials 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- MNZMECMQTYGSOI-UHFFFAOYSA-N acetic acid;hydron;bromide Chemical compound Br.CC(O)=O MNZMECMQTYGSOI-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000003855 acyl compounds Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007275 deallylation reaction Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- ZRSDQBKGDNPFLT-UHFFFAOYSA-N ethanol;oxolane Chemical compound CCO.C1CCOC1 ZRSDQBKGDNPFLT-UHFFFAOYSA-N 0.000 description 1
- 150000002373 hemiacetals Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- QMYTXCUSWCFXLY-UHFFFAOYSA-N methanol;triethylazanium;hydroxide Chemical compound [OH-].OC.CC[NH+](CC)CC QMYTXCUSWCFXLY-UHFFFAOYSA-N 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007530 organic bases Chemical group 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- SUBJHSREKVAVAR-UHFFFAOYSA-N sodium;methanol;methanolate Chemical compound [Na+].OC.[O-]C SUBJHSREKVAVAR-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- PIILXFBHQILWPS-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC PIILXFBHQILWPS-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Description
本発明は新規な複合多糖およびその製造法に関
する。
細胞表層の糖蛋白質は、糖鎖を外側に配向して
存在し、生物情報マーカーとして機能している。
糖蛋白質の糖鎖の中で、蛋白質部分とＮ−グリコ
シド結合している糖鎖が最も複雑な構造を有して
おり、現在までに種々の分枝構造が知られてい
る。本発明者らは、３重分枝をもつ複合型糖鎖の
６糖単位の合成に成功している（T.Ogawa，S.
Nakabayashi，Carbohydrate Res.，93（1981）
c1）。本発明者らは更に、に示すような２重分
枝を有する複合型糖鎖の９糖単位構造(1)の合成を
目的として研究を進め、本発明を完成するに至つ
た。
本発明の化合物は次の一般式(1)で表わされる。
上記式中、Acはアセチル基、R1は水素原子ま
たはアセチル基、R2は水素原子またはベンジル
基、R3は水素原子、R4は水素原子またはアセチ
ル基を示し、またR3とR4は共同してフタロイル
基を形成してもよい。
上記複合多糖は式(3)
（式中、Acはアセチル基、Ｘはハロゲン原子
を示す）
で表わされる化合物と、式(2)
（式中、Bnはベンジル基、R3は水素原子、R4
はアセチル基を示し、またR3とR4は共同してフ
タロイル基を形成してもよい）
で表わされる化合物を反応させ、必要により脱ア
セチル化、脱ベンジル化、脱フタロイル化および
アセチル化することにより得られる。
以下本発明を更に詳細に説明する。
(i) ３糖受容体(2)の合成
３糖受容体(2)はたとえばスキーム１に示すよう
に合成することができる。
まず化合物(4)トリブチルスズ化して化合物(5)と
し、次にテトラブチルアンモニウムブロマイド存
在下にベンジルブロマイドを、90℃で２日間作用
させると、３，６−ベンジル体(6)が得られる。こ
れをアセチル化して化合物(7)とし、さらにAcOH
−AcONa水溶液中、PdCl2により脱アリル化し
て化合物(8)を得る。CH2Cl2中、触媒量のDMF存
在下に化合物(8)をSOCl2で処理するとクロライド
(9)が定量的に得られる。AgOSO2CF3とモレキユ
ラーシーブス4A末存在下に化合物(10)（T.
Ogawa，S.Nakabayashi，Carbohydr.Res.，97
（1981）81〜86）と化合物(9)を反応させるとキト
ビオシル誘導体(11)が得られる。これを脱アセチル
化して化合物(12)とする。
一方、アセテート(13)（T.Ogawa，S.
Nakabayashi，Carbohydr.Res.，93（1981）C1−
C5）を加水分解してヘミアセタール(14)とし、こ
れをｐ−ニトロベンゾイルクロライドにより処理
してアシル体(15)を得、さらにCH2Cl2中、HBrで
処理してブロマイド(16)を得る。
Ag−シリケート（H.Paulsen，O.Lockhoff，
Chem.Ber.，114（1981）3102−3114；H.
Paulsen，R.Lebuhn，O.Lockhoff，Carbohydr.
Res.，103（1982）C7−C11）とモレキユラーシー
ブズ5A末存在下に２糖供与体(12)とブロマイド(16)
を反応させるとβ−アノマー(17)とα−アノマ−(19)
が得られる。β−アノマー(17)をPdCl2／AcOH−
AcONa水溶液中で処理して脱アリル体(18)とす
る。これをさらに１）１：1BuNH2−MeOH、
90℃、８日、２）Ac2O−ピリジン、３）
NaOMe−MeOH処理すると３糖受容体２が得ら
れる。また脱アリル体(18)を化合物(2)の代りに糖受
容体として使用してもよい。この場合には、９糖
の合成後、必要により、脱フタロイル化、アセチ
ル化、脱アセチル化および脱ベンジル化を行えば
よい。
(ii) ３糖供与体(3)の合成
３糖供与体(3)はたとえばスキーム２に示すよう
に合成することができる。
まず化合物（24）を、AgOSO2CF3とモレキユ
ラ−シーブス4A末の存在下に２糖供与体（25）
と反応させて３顛（26）を得る。３糖（26）をさ
らに１）NaOMe／MeOH、２）MeOH−
BuNH2、３）Ac2O−ピリジンで処理すると、化
合物（27）および（28）を経由して、化合物
（29）が得られる。これをPd−Ｃ／AcOHで脱ベ
ンジル化して化合物（31）とし、さらにアセチル
化するとアセチル体（31）が得られる。これを
HBr／AcOH−CH2Cl2で処理して３糖供与体(3)
を得る。
化合物（24）はたとえば、T.Ogawa，H.
Yamamoto，Carbohydr.Res.，104（1982）271−
283記載の方法により合成することができる。ま
た化合物（25）は、M.M.Ponpipom，R.L.
Bugianesi，T.Y.Shen，Tetrahedron.Lett.，
（1978）1717−1720；J.Arnarp，J.Lonngren，J.
Chem.Commun.，（1980）1000−1002；J.Chem.
Soc.Perkin Trans.1，（1981）2070−2074；T.
Ogawa，S.Nakabayashi，Carbohydr.Res.，97
（1981）81−86；R.U.Lemieux.S.Z.Abbas，B.Y.
Chung，Can，J.Chem.，60（1982）58−62.記載
の方法により合成することができる。
(iii) 目的化合物(i)の合成
本発明の目的化合物(1)は、工程(i)および(ii)によ
り合成される３糖受容体(2)と３糖供与体(3)を反応
させることにより得られる。３糖受容体として化
合物(2)の代りに化合物(18)を用いてもよいことはす
でに説明したとおりである。化合物(2)または(18)
と、化合物(3)との反応は１，２−ジクロルエタ
ン、ジクロルメタン、クロロホルム、ニトロメタ
ン、ベンセン、トルエン等の溶媒中、温度−20℃
〜150℃、時間１〜30時間程度で、HgBr2、Hg
（CN）2、AgOSO2CF3、Ag2CO3、Ag2O、
AgClO4等の触媒を用いて行われる。この際、反
応中生成するHBrなどの酸を除去する目的でテ
トラメチルウレア、ジ−イソプロピルエチルアミ
ンなどの三級アミン、モレキユラ−シーブ4Aな
どを加えて反応させるのが好ましい。また化合物
(3)としてブロマイドの例を示したが、クロライド
またはアイオダイドであつてもよい。この反応で
は、糖受容体１モルに対して糖供与体２モルが反
応するか、糖供与体を過剰に、たとえば、６モル
程度使用することが好ましい。
糖受容体として化合物(2)を用いた場合、９糖化
合物（1a）が得られる。これを脱アセチル化す
ると化合物（1b）が、さらに脱ベンジル化する
と化合物（1c）が得られる。また糖受容体として
化合物(18)を用いた場合、９糖化合物（1d）が得
られる。これをたとえばBuNH2−MeOHで処理
すれば脱フタロイル体（1e）が得られる。これを
アセチル化すれば化合物（1a）が得られる。
化合物（1a）、（1d）等の脱アセチル化反応は、
ナトリウムメトキシド、ナトリウムエトキシド、
トリエチルアミンなどの三級有機塩基等の触媒を
用いて、メタノール、エタノール、ｎ−及びiso
−プロパノール、水又はそれらの混合溶液中温度
−20℃〜100℃、0.5時間〜30時間で充分に進行す
る。
化合物（1a）、（1b）、（1d）、（1e）等の脱ベン
ジル化反応は、水−エタノール、THF−エタノ
ール、エタノール、メタノール、酢酸、THF−
水、ジオキサン−水、DMF等の溶媒又は混合溶
媒に溶解し、Pd／Ｃ等を触媒として常圧又は加
圧水素添加することにより行われる。反応温度は
０℃〜100℃反応時間は１〜100時間程度が適当で
ある。
なお、上記の工程において得られる中間体及び
目的化合物（1a）、（1b）、（1c）、（1d）、（1e）、
(2)、(3)、(4)、(5)、(6)、(7)、(8)、(9)、(11)、(12)
、(14)、
(15)、(16)、(17)、(18)、(19)、（26）、（27）、（28
）、（29）、
（30）、（31）はいずれも本発明者らにより初めて
合成された新規化合物である。
本発明により得られる上記の新規化合物は、細
胞表層糖蛋白質を合成する際の中間体として、
又、細胞表層糖蛋白質の生物学的意義や機能を解
明する際の試薬としての有用性を有するものであ
る。
以下実施例により本発明を更に詳細に説明する
が、これらは何ら本発明の範囲を制限するもので
はない。
なお、以下の実施例および参考例において、特
に明記しない限り、旋光度〔α〕Dの測定はCHCl3
中25℃で行つた。
参考例 １
３糖受容体の合成
(a) 化合物（4′）10.0ｇを80％aq.AcOH200mlに
溶解し、80℃で1.5hr撹拌した。そして反応液
を減圧濃縮して、その残渣をシリカゲル450ｇ
のカラム（展開溶媒CHCl3／MeOH＝20／１）
に通して精製し、シロツプ状の化合物(4)を6.56
ｇ（収率78.8％）得た。
〔化合物(4)の性質〕
TLC Rf＝0.61（CHCl3／MeOH＝10／１）
Anal（元素分析）Calcd.（計算値）（％）
C24H25NO7：Ｃ，65.59；Ｈ，5.73；Ｎ，
3.19
Found（測定値）（％）：
Ｃ，65.74；Ｈ，5.82；Ｎ，3.03
〔α〕22.5 D＋40.3゜（C0.62，CHCl3）
(b) 化合物(4)8.8ｇ（20.0mmol）にトルエン200
mlと（ｎ−Bu3Sn）2O8.95ｇ（15.0mmol）を加
え、浴温140℃で4hr還流させた。その間生成し
たH2Oをトルエン100mlといつしよに系外に除
去した。冷却後、反応液にBnBr7.14ml
（60.0mmol）とｎ−Bu4NBr3.23ｇ
（10.0mmol）を加え、アルゴン下浴温90℃で
19hr撹拌した。さらにBnBr7.14mlとｎ−
Bu4NBr3.23ｇを加え、90℃で22hr撹拌した。
そして反応後を減圧濃縮し、残渣を酢エチ（酢
酸エチル）600mlに溶解して、KF30ｇと水300
mlを加え、有機スズを沈殿させた。過後分液
して、有機層を水洗し、MgSO4で乾燥した。
過後、減圧濃縮して、残渣をシリカゲル450
ｇのカラム（展開溶媒トルエン／酢エチ＝10／
１）に通して精製し、シロツプ状の化合物(6)を
7.99ｇ得た（収率75.4％）。
〔化合物(6)の性質〕
TLC Rf＝0.47（トルエン／酢エチ＝３／１）
Anal.Calcd.（％）C31H31NO7：
Ｃ，70.30；Ｈ，5.90；Ｎ，2.65
Found（％）；Ｃ，69.85；Ｈ，5.99；Ｎ，2.54
〔α〕22.5 D＋33.8゜（CO.71，CHCl3）
(c) 化合物(6)7.7ｇをピリジン40mlに溶解し、
Ac2O40mlを加えて、室温で17hr撹拌した。そ
して、反応液を減圧濃縮し、残渣をシリカゲル
400ｇのカラム（展開溶媒トルエン／酢エチ＝
10／１）に通して精製し、シロツプ状物質(7)を
8.2ｇ得た（収率98.8％）。
〔化合物(7)の性質〕
TLC Rf＝0.49（トルエン／酢エチ＝５／１）
Anal.Calcd.（％）C33H33NO8：
Ｃ，69.34；Ｈ，5.82；Ｎ，2.45
Found（％）；Ｃ，69.37；Ｈ，5.87；Ｎ，2.34
〔α〕22.5 D＋64.4゜（C0.55，CHCl3）
(d) 化合物(7)8.2ｇ（14.3mmol）を95％aq.
AcOH100mlに溶解し、PdCl22.8ｇ
（15.8mmol）とAcONa2.8ｇ（34.1mmol）を
加えて、70℃で2hr撹拌した。反応終了後、反
応液を減圧濃縮し、残渣を酢エチ300mlに溶解
して飽和重曹水100mlを加えセライト過した。
液を分液して、有機層をMgSO4で乾燥し、
過後、減圧濃縮して、その残渣をシリカゲル
400ｇのカラム（展開溶媒トルエン／酢エチ＝
３／１）に通して精製し、結晶(8)を6.3ｇを得
た（収率82.9％）。
〔化合物(8)の性質〕
TLC Rf＝0.35（トルエン／酢エチ＝２／１）
Anal.Calcd.（％）C30H29NO8：
Ｃ，67.78；Ｈ，5.50；Ｎ，2.64
Found（％）；Ｃ，68.02；Ｈ，5.65；Ｎ，2.50
〔α〕24.5 D＋82.6゜（C0.62，CHCl3）
m.p. 102〜104℃
(e) 化合物(8)6.4ｇ（12mmol）をジクロルエタン
100mlに溶解し、SOCl210mlとDMF1滴を加え
て、室温で2hr撹拌した。そして、DMFの除去
のためにシリカゲル100mgを加え、さらに、ト
ルエン50mlを加えて過した後、浴温40℃で減
圧濃縮してシロツプ状化合物(9)を得た。このシ
ロツプを精製することなしに次の反応に用い
た。
〔化合物(9)の性質〕
TLC Rf＝0.58（トルエン／酢エチ＝５／１）
(f) 190℃で24hr真空乾燥したMS−4A粉末18ｇ
に、AgOSO2CF39.3ｇ（36mmol）と１，２−
ジクロルエタン50mlを加え、系内をアルルゴン
置換した。次に、１，２−ジクロルエタン20ml
に溶解した受容体(10)3.5ｇ（6mmol）を加えて、
０℃で1hr撹拌した。そして、１，２−ジクロ
ルエタン20mlに溶解した。供与体(9)（12mmol
相当）を滴下した。反応は０℃→R.T.（室温）
で17hr行なつた。反応終了後、CH2Cl2500mlを
加えてセライト過し、水洗、重曹処理をして
有機層をMgSO4乾燥した。過後、減圧濃縮
して、その残渣をシリカゲル800ｇのカラム
（展開溶媒トルエン／酢エチ＝10／１）に通し
て精製し、シロツプ状の化合物(11)を4.1ｇ得た
（収率62.1％）。
〔化合物(11)の性質〕
TLC Rf＝0.50（トルエン／酢エチ＝５／１）
Anal.Calcd.（％）C65H69N2O14：
Ｃ，71.41；Ｈ，5.53；Ｎ，2.56
Found（％）；Ｃ，71.04；Ｈ，5.53；Ｎ，2.58
〔α〕24 D＋15.9゜（C1.13，CHCl3）
(g) 化合物(11)4.0ｇをアセトン200mlに溶解し、
H2O8mlと36％HCl4mlを加えて、浴温80℃で４
日間還流した。そして、減圧濃縮し、残渣を酢
エチ300mlに溶解して重曹処理を行ない、有機
層をMgSO4乾燥した。過後、減圧濃縮して、
その残渣をシリカゲル400ｇのカラム（展開溶
媒トルエン／酢エチ＝７／１）に通して精製
し、シロツプ状の化合物(12)を3.1ｇ得た（収率
81.6％）。
〔化合物(12)の性質〕
TLC Rf＝0.50（トルエン／酢エチ＝３／１）
Anal.Calcd.（％）C63H58N2O13：
Ｃ，71.98；Ｈ，5.56；Ｎ，2.67
Found（％）；Ｃ，71.97；Ｈ，5.57；Ｎ，2.61
〔α〕24 D−7.8゜（C1.06，CHCl3）
(h) 化合物(13)（T.Ogawa，S.Nakabayashi，
Carbohydr.Res.，93（1981）C1−C5；T.
Ogawa，S.Nakabayashi，T.Kitajima，
Carbohydr.Res.，114（1983）225−236）8.8ｇ
をMeOH−H2O−Et3N（４：１：３）180mlに
溶解し、さらにTHF60mlを加えて、室温で
19hr撹拌した。そして、減圧濃縮して、その残
渣をシリカゲル400ｇのカラム（展開溶媒トル
エン／酢エチ＝５／１）に通して精製し、シロ
ツプ状の化合物(14)を6.8ｇ得た（収率85.0％）。
〔化合物(14)の性質〕
TLC Rf＝0.45（トルエン／酢エチ＝２／１）
Anal.Calcd.（％）C26H32O6：
Ｃ，70.89；Ｈ，7.32
Found（％）；Ｃ，70.90；Ｈ，7.38
〔α〕22 D＋31.0゜（C1.14，CHCl3）
(i) 化合物(14)1019.2mg（2.3mmol）をCH2Cl220ml
に溶解した後氷冷し、ピリジン２mlと
The present invention relates to a novel complex polysaccharide and a method for producing the same. Glycoproteins on the cell surface exist with sugar chains oriented outward, and function as biological information markers.
Among the sugar chains of glycoproteins, sugar chains that have N-glycoside bonds with protein moieties have the most complex structure, and various branched structures are known to date. The present inventors have succeeded in synthesizing a hexasaccharide unit of a complex glycan with triple branches (T. Ogawa, S.
Nakabayashi, Carbohydrate Res., 93 (1981)
c1). The present inventors further conducted research with the aim of synthesizing the 9-saccharide unit structure (1) of a complex type sugar chain having double branches as shown in Figure 1, and completed the present invention. The compound of the present invention is represented by the following general formula (1). In the above formula, Ac is an acetyl group, R 1 is a hydrogen atom or an acetyl group, R 2 is a hydrogen atom or a benzyl group, R 3 is a hydrogen atom, R 4 is a hydrogen atom or an acetyl group, and R 3 and R 4 may jointly form a phthaloyl group. The above complex polysaccharide has the formula (3) (In the formula, Ac represents an acetyl group and X represents a halogen atom) and a compound represented by the formula (2) (In the formula, Bn is a benzyl group, R 3 is a hydrogen atom, R 4
represents an acetyl group, and R 3 and R 4 may jointly form a phthaloyl group), and if necessary, deacetylate, debenzylate, dephthaloylate, and acetylate. It can be obtained by The present invention will be explained in more detail below. (i) Synthesis of trisaccharide receptor (2) Trisaccharide receptor (2) can be synthesized, for example, as shown in Scheme 1. First, compound (4) is converted to tributyltin to give compound (5), and then benzyl bromide is treated in the presence of tetrabutylammonium bromide at 90°C for 2 days to obtain 3,6-benzyl compound (6). This is acetylated to form compound (7), and then AcOH
Compound (8) is obtained by deallylation with PdCl 2 in an AcONa aqueous solution. Treatment of compound (8) with SOCl 2 in the presence of a catalytic amount of DMF in CH 2 Cl 2 yields the chloride.
(9) can be obtained quantitatively. Compound ( 10) ( T.
Ogawa, S. Nakabayashi, Carbohydr.Res., 97
(1981) 81-86) and compound (9), chitobiosyl derivative (11) is obtained. This is deacetylated to give compound (12). On the other hand, acetate (13) (T.Ogawa, S.
Nakabayashi, Carbohydr.Res., 93 (1981) C1−
C5) was hydrolyzed to give the hemiacetal (14), which was treated with p-nitrobenzoyl chloride to obtain the acyl compound (15), which was further treated with HBr in CH 2 Cl 2 to give the bromide (16). obtain. Ag-Silicate (H.Paulsen, O.Lockhoff,
Chem.Ber., 114 (1981) 3102-3114; H.
Paulsen, R. Lebuhn, O. Lockhoff, Carbohydr.
Res., 103 (1982) C7-C11) and disaccharide donor (12) and bromide (16) in the presence of molecular sieves 5A end.
When reacting, β-anomer (17) and α-anomer (19)
is obtained. β-anomer (17) was converted into PdCl 2 /AcOH−
The deallylated product (18) is obtained by treatment in an AcONa aqueous solution. This is further 1) 1:1BuNH 2 -MeOH,
90°C, 8 days, 2) Ac 2 O-pyridine, 3)
NaOMe-MeOH treatment yields trisaccharide receptor 2. Moreover, deallylated compound (18) may be used as a sugar acceptor instead of compound (2). In this case, after the synthesis of the 9-saccharide, defthaloylation, acetylation, deacetylation, and debenzylation may be performed as necessary. (ii) Synthesis of trisaccharide donor (3) Trisaccharide donor (3) can be synthesized, for example, as shown in Scheme 2. First, compound (24) was added to disaccharide donor (25) in the presence of AgOSO 2 CF 3 and molecular sieves 4A end.
React with to obtain 3 pieces (26). Trisaccharide (26) is further converted into 1) NaOMe/MeOH, 2) MeOH−
When treated with BuNH 2 , 3) Ac 2 O-pyridine, compound (29) is obtained via compounds (27) and (28). This is debenzylated with Pd-C/AcOH to give compound (31), and further acetylated to obtain acetyl compound (31). this
Treated with HBr/AcOH-CH 2 Cl 2 to form trisaccharide donor (3)
get. Compound (24), for example, is described by T. Ogawa, H.
Yamamoto, Carbohydr.Res., 104 (1982) 271−
It can be synthesized by the method described in 283. Compound (25) is MMPonpipom, RL
Bugianesi, TYShen, Tetrahedron.Lett.,
(1978) 1717−1720; J.Arnarp, J.Lonngren, J.
Chem.Commun., (1980) 1000−1002; J.Chem.
Soc. Perkin Trans. 1, (1981) 2070−2074; T.
Ogawa, S. Nakabayashi, Carbohydr.Res., 97
(1981) 81-86; RULemieux.SZAbbas, BY
It can be synthesized by the method described in Chung, Can, J.Chem., 60 (1982) 58-62. (iii) Synthesis of target compound (i) The target compound (1) of the present invention is obtained by reacting the trisaccharide acceptor (2) synthesized by steps (i) and (ii) with the trisaccharide donor (3). It can be obtained by As already explained, compound (18) may be used instead of compound (2) as the trisaccharide receptor. Compound (2) or (18)
The reaction with compound (3) is carried out in a solvent such as 1,2-dichloroethane, dichloromethane, chloroform, nitromethane, benzene, toluene, etc. at a temperature of -20°C.
HgBr 2 , Hg at ~150℃ for 1 to 30 hours
(CN) 2 , AgOSO 2 CF 3 , Ag 2 CO 3 , Ag 2 O,
It is carried out using a catalyst such as AgClO4 . At this time, it is preferable to add a tertiary amine such as tetramethylurea, di-isopropylethylamine, molecular sieve 4A, etc. to the reaction mixture in order to remove acids such as HBr generated during the reaction. Also compounds
Although bromide is shown as an example as (3), chloride or iodide may also be used. In this reaction, it is preferable that 2 moles of the sugar donor react with 1 mole of the sugar acceptor, or that the sugar donor be used in excess, for example, about 6 moles. When compound (2) is used as a sugar acceptor, a nonasaccharide compound (1a) is obtained. Deacetylation of this yields compound (1b), and further debenzylation yields compound (1c). Furthermore, when compound (18) is used as a sugar acceptor, a nonasaccharide compound (1d) is obtained. If this is treated with, for example, BuNH 2 -MeOH, the dephthaloyl compound (1e) can be obtained. Acetylation of this yields compound (1a). The deacetylation reaction of compounds (1a), (1d), etc.
sodium methoxide, sodium ethoxide,
Using catalysts such as tertiary organic bases such as triethylamine, methanol, ethanol, n- and iso
- The process proceeds satisfactorily in a solution of propanol, water or a mixture thereof at a temperature of -20°C to 100°C for 0.5 to 30 hours. The debenzylation reaction of compounds (1a), (1b), (1d), (1e), etc. can be carried out using water-ethanol, THF-ethanol, ethanol, methanol, acetic acid, THF-
It is carried out by dissolving in a solvent or mixed solvent such as water, dioxane-water, DMF, etc., and hydrogenating at normal pressure or under pressure using Pd/C or the like as a catalyst. Appropriate reaction temperature is 0°C to 100°C and reaction time is approximately 1 to 100 hours. In addition, the intermediates and target compounds (1a), (1b), (1c), (1d), (1e) obtained in the above steps,
(2), (3), (4), (5), (6), (7), (8), (9), (11), (12)
,(14),
(15), (16), (17), (18), (19), (26), (27), (28
), (29),
Both (30) and (31) are new compounds synthesized for the first time by the present inventors. The above novel compound obtained by the present invention can be used as an intermediate in the synthesis of cell surface glycoproteins.
It is also useful as a reagent for elucidating the biological significance and function of cell surface glycoproteins. The present invention will be explained in more detail with reference to Examples below, but these are not intended to limit the scope of the present invention in any way. In addition, in the following examples and reference examples, unless otherwise specified, the optical rotation [α] D is measured using CHCl 3
It was carried out at 25°C. Reference example 1 Synthesis of trisaccharide receptor (a) 10.0 g of compound (4') was dissolved in 200 ml of 80% aq. AcOH and stirred at 80°C for 1.5 hours. Then, the reaction solution was concentrated under reduced pressure, and the residue was converted into 450 g of silica gel.
column (developing solvent CHCl 3 /MeOH=20/1)
The syrupy compound (4) was purified by
g (yield 78.8%) was obtained. [Properties of compound (4)] TLC Rf=0.61 (CHCl 3 /MeOH=10/1) Anal (elemental analysis) Calcd. (calculated value) (%)
C 24 H 25 NO 7 :C, 65.59; H, 5.73; N,
3.19 Found (measured value) (%): C, 65.74; H, 5.82; N, 3.03 [α] 22.5 D +40.3° (C0.62, CHCl 3 ) (b) Compound (4) 8.8 g (20.0 mmol ) toluene 200
ml and 8.95 g (15.0 mmol) of (n-Bu 3 Sn) 2 O were added, and the mixture was refluxed for 4 hours at a bath temperature of 140°C. The H 2 O produced during that time was removed from the system with 100 ml of toluene. After cooling, add 7.14ml of BnBr to the reaction solution.
(60.0mmol) and n-Bu 4 NBr3.23g
(10.0 mmol) was added, and the bath temperature was 90℃ under argon.
Stirred for 19 hours. Furthermore, BnBr7.14ml and n-
3.23 g of Bu 4 NBr was added and stirred at 90°C for 22 hours.
After the reaction was concentrated under reduced pressure, the residue was dissolved in 600 ml of ethyl acetate, and 30 g of KF and 300 ml of water were dissolved.
ml was added to precipitate the organotin. After filtration, the organic layer was washed with water and dried over MgSO 4 .
After filtration, concentrate under reduced pressure and transfer the residue to silica gel 450.
g column (developing solvent toluene/ethyl acetate = 10/
1) to obtain syrupy compound (6).
7.99g was obtained (yield 75.4%). [Properties of compound (6)] TLC Rf = 0.47 (Toluene/ethyl acetate = 3/1) Anal. Calcd. (%) C 31 H 31 NO 7 : C, 70.30; H, 5.90; N, 2.65 Found (% ); C, 69.85; H, 5.99; N, 2.54 [α] 22.5 D +33.8° (CO.71, CHCl 3 ) (c) Dissolve 7.7 g of compound (6) in 40 ml of pyridine,
40 ml of Ac 2 O was added and stirred at room temperature for 17 hours. Then, the reaction solution was concentrated under reduced pressure, and the residue was purified using silica gel.
400g column (developing solvent toluene/ethyl acetate =
10/1) to purify the syrupy substance (7).
8.2g was obtained (yield 98.8%). [Properties of compound (7)] TLC Rf = 0.49 (Toluene/ethyl acetate = 5/1) Anal. Calcd. (%) C 33 H 33 NO 8 : C, 69.34; H, 5.82; N, 2.45 Found (% ); C, 69.37; H, 5.87; N, 2.34 [α] 22.5 D +64.4° (C0.55, CHCl 3 ) (d) 8.2 g (14.3 mmol) of compound (7) was added to 95% aq.
2.8 g of PdCl 2 dissolved in 100 ml of AcOH
(15.8 mmol) and 2.8 g (34.1 mmol) of AcONa were added, and the mixture was stirred at 70°C for 2 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure, the residue was dissolved in 300 ml of ethyl acetate, 100 ml of saturated sodium bicarbonate solution was added, and the mixture was filtered through Celite.
Separate the liquid and dry the organic layer with MgSO4 .
After filtration, concentrate under reduced pressure and transfer the residue to silica gel.
400g column (developing solvent toluene/ethyl acetate =
3/1) to obtain 6.3 g of crystal (8) (yield: 82.9%). [Properties of compound (8)] TLC Rf = 0.35 (toluene/ethyl acetate = 2/1) Anal. Calcd. (%) C 30 H 29 NO 8 : C, 67.78; H, 5.50; N, 2.64 Found (% ); C, 68.02; H, 5.65; N, 2.50 [α] 24.5 D +82.6° (C0.62, CHCl 3 ) mp 102-104°C (e) 6.4 g (12 mmol) of compound (8) was dissolved in dichloroethane
The solution was dissolved in 100 ml, 10 ml of SOCl 2 and 1 drop of DMF were added, and the mixture was stirred at room temperature for 2 hours. Then, 100 mg of silica gel was added to remove DMF, and 50 ml of toluene was added and filtered, followed by concentration under reduced pressure at a bath temperature of 40°C to obtain a syrupy compound (9). This syrup was used in the next reaction without purification. [Properties of compound (9)] TLC Rf = 0.58 (toluene/ethyl acetate = 5/1) (f) 18 g of MS-4A powder vacuum dried at 190°C for 24 hours
9.3 g (36 mmol) of AgOSO 2 CF 3 and 1,2-
50 ml of dichloroethane was added to replace the system with arurgone. Next, 20ml of 1,2-dichloroethane
Add 3.5 g (6 mmol) of receptor (10) dissolved in
The mixture was stirred at 0°C for 1 hour. Then, it was dissolved in 20 ml of 1,2-dichloroethane. Donor (9) (12mmol
equivalent) was added dropwise. Reaction: 0℃→RT (room temperature)
I did it for 17 hours. After the reaction was completed, 500 ml of CH 2 Cl 2 was added, the mixture was filtered through Celite, washed with water, treated with sodium bicarbonate, and the organic layer was dried over MgSO 4 . After filtration, it was concentrated under reduced pressure, and the residue was purified by passing it through a column of 800 g of silica gel (developing solvent: toluene/ethyl acetate = 10/1) to obtain 4.1 g of syrup-like compound (11) (yield 62.1%). . [Properties of compound (11)] TLC Rf = 0.50 (Toluene/ethyl acetate = 5/1) Anal. Calcd. (%) C 65 H 69 N 2 O 14 : C, 71.41; H, 5.53; N, 2.56 Found (%); C, 71.04; H, 5.53; N, 2.58 [α] 24 D +15.9° (C1.13, CHCl 3 ) (g) Dissolve 4.0 g of compound (11) in 200 ml of acetone,
Add 8 ml of H 2 O and 4 ml of 36% HCl and boil at a bath temperature of 80°C.
It was refluxed for days. Then, it was concentrated under reduced pressure, the residue was dissolved in 300 ml of ethyl acetate, treated with sodium bicarbonate, and the organic layer was dried with MgSO 4 . After filtration, concentrate under reduced pressure.
The residue was purified by passing through a 400 g column of silica gel (developing solvent: toluene/ethyl acetate = 7/1) to obtain 3.1 g of syrupy compound (12) (yield:
81.6%). [Properties of compound (12)] TLC Rf = 0.50 (Toluene/ethyl acetate = 3/1) Anal. Calcd. (%) C 63 H 58 N 2 O 13 : C, 71.98; H, 5.56; N, 2.67 Found (%); C, 71.97; H, 5.57; N, 2.61 [α] 24 D −7.8° (C1.06, CHCl 3 ) (h) Compound (13) (T. Ogawa, S. Nakabayashi,
Carbohydr.Res., 93 (1981) C1−C5; T.
Ogawa, S.Nakabayashi, T.Kitajima,
Carbohydr.Res., 114 (1983) 225-236) 8.8g
Dissolve in 180 ml of MeOH-H 2 O-Et 3 N (4:1:3), add 60 ml of THF, and stir at room temperature.
Stirred for 19 hours. Then, it was concentrated under reduced pressure, and the residue was purified by passing it through a column of 400 g of silica gel (developing solvent: toluene/ethyl acetate = 5/1) to obtain 6.8 g of syrup-like compound (14) (yield: 85.0%). . [Properties of compound (14)] TLC Rf = 0.45 (toluene/ethyl acetate = 2/1) Anal. Calcd. (%) C 26 H 32 O 6 : C, 70.89; H, 7.32 Found (%); C, 70.90; H, 7.38 [α] 22 D +31.0° (C1.14, CHCl 3 ) (i) 1019.2 mg (2.3 mmol) of compound (14) in 20 ml of CH 2 Cl 2
After dissolving in water, cool on ice and add 2 ml of pyridine
α−アノマー β−アノマー
TLC Rf（トルエン／酢エチ＝10／１）
0.52 0.43
Anal.Calcd.（％）C33H35NO9：
Ｃ，67.22 67.20 67.37
Ｈ， 5.98 5.98 5.99
Ｎ， 2.38 2.35 2.35
〔α〕24.5 D（C0.61，CHCl3）＋52.5゜―
(j) α，β混合物(15)6.6ｇ（11.2mmol）を
CH2Cl2100mlに溶解した後氷冷し、飽和HBr−
CH2Cl230mlを加えて、０℃で20min.撹拌した。
そして、析出した
α-anomer β-anomer TLC Rf (toluene/ethyl acetate = 10/1)
0.52 0.43 Anal.Calcd. (%) C 33 H 35 NO 9 : C, 67.22 67.20 67.37 H, 5.98 5.98 5.99 N, 2.38 2.35 2.35 [α] 24.5 D (C0.61, CHCl 3 ) + 52.5° ― ( j) 6.6g (11.2mmol) of α,β mixture (15)
After dissolving in 100 ml of CH 2 Cl 2 and cooling on ice, saturated HBr−
30 ml of CH 2 Cl 2 was added and stirred at 0° C. for 20 min.
And it precipitated
TLC Rf＝0.64（トルエン／酢エチ＝10／１）
(k) Ag−シリケート12ｇとMS−5A粉末10ｇを
混合し、190℃で19hr真空乾燥した。冷却後、
アルゴン置換して１，２−ジクロルエタン80ml
を加え、さらに１，２−ジクロルエタン20mlに
溶解した受容体(16)2.9ｇ（2.8mmol）を加えて
室温で1hr撹拌した。次に氷冷して、１，２−
ジクロルエタン20mlに溶解した供与体(16)
（11.2mmol相当）を加え、０℃→R.T.／16hr撹
拌した。反応終了後、CH2Cl2500mlを加えてセ
ライト過し、水洗、重曹処理をして、有機層
をMgSO4乾燥した。過後、減圧濃縮して、
その残渣をシリカゲル850ｇのカラム（展開溶
媒トルエン／酢エチ＝10／１）に通して精製
し、β−アノマー(17)1.62ｇ（39.8％）、α−ア
ノマー(19)1.45ｇ（35.6％）をそれぞれシロツプ
で得た。
β−アノマー(17) α−アノマー(19)
TLC Rf（トルエン／酢エチ＝５／１）
0.47 0.53
Anal.Calcd.（％）C89H88N2O18：
Ｃ，72.54 72.61 72.87
Ｈ， 6.02 6.15 6.06
Ｎ， 1.90 1.75 1.82
〔α〕27.5 D（CHCl3） −2.1゜ ＋15.6゜
（C1.02）（C1.17）
CMRδC：β−アノマー(17)
97.03（Ｃ−1a，Ｃ−1b，1JCH164.8Hz）
101.47（Ｃ−1c，1JCH156.3Hz）
α−アノマー(19)96.74（Ｃ−1aまたはＣ−1b，
1JCH164.8Hz）
97.13（Ｃ−1aまたはＣ−1b，1JCH164.8Hz）
100.11（Ｃ−1c，1JCH169.7Hz）
(l) 化合物(17)1369.0mg（0.93mmol）を95％aq.
AcOH30mlに溶解し、PdCl2362.4mg
（2.04mmol）とAcONa365.8mg（4.46mmol）
を加えて、70℃で1hr撹拌した。そして、反応
液を減圧濃縮し、残渣を酢エチ100mlに溶解し
て飽和重曹水を加え、セライト過後分液し
て、有機層をMgSO4乾燥した。過後、減圧
濃縮して、その残渣をシリカゲル140ｇのカラ
ム（展開溶媒トルエン／酢エチ＝４／１）に通
して精製し、シロツプ状の化合物(18)を747.8mg
得た（収率57.7％）。
〔化合物(18)の性質〕
TLC Rf＝0.55（トルエン／酢エチ＝２／１）
Anal.Calcd.（％）C83H80N2O18：
Ｃ，71.53；Ｈ，5.79；Ｎ，2.01
Found（％）；Ｃ，71.87；Ｈ，5.91；Ｎ，1.88
〔α〕27 D−4.5゜（C1.38，CHCl3）
(m) 化合物(18)150mg（0.108mmol）の入つたフラ
スコの中にMeOH5c.c.、BuNH25c.c.を入れ50℃
で１晩加熱撹拌した。その後、浴温を還流温度
（90℃〜100℃）まで上げ、７日間加熱撹拌し
た。この間１日ごとにMeOH：BuNH2＝１：
１の溶液４c.c.を加えた。反応溶液をアミン臭が
しなくなるまで減圧濃縮した。
残渣をピリジン２c.c.Ac2O2c.c.に溶かし、室温
で１晩撹拌放置した。反応液はEtOHと共沸さ
せて減圧濃縮し、残渣をSiO25.0ｇCH2Cl2：ア
セトン＝５：１でカラムクロマトし、SiO2の
まざつた目的物を含む区分200mgを得る。（Rf
＝0.74、CH2Cl2：アセトン＝５：１）
上記区分をMeOH4c.c.、1NNaOMe／MeOH
溶液20滴により脱アセチル化を行う。１晩室温
撹拌し、アンバーリストＡ−15で反応溶液を中
和後過、減圧濃縮し、残渣をSiO210ｇ
CH2Cl2：アセトン＝10：１でシリカゲルクロ
マトグラフイーを行い化合物(2)117mgを得る。
〔化合物(2)の性質〕
TLC Rf＝0.47（CH2Cl2／アセトン＝３／１）
Anal.Calcd.（％）C71H80N2O16・H2O：Ｃ，
69.02；Ｈ，6.69；Ｎ，2.27
Found（％）；Ｃ，69.08；Ｈ，6.62；Ｎ，2.26
〔α〕25 D−38.7゜（C0.84，CHCl3）
CMR δC：101.23（Ｃ−1c，1JCH156.3Hz）
99.86（Ｃ−1ab，1JCH162.4Hz）
参考例 ２
３糖供与体の合成
(a) 190℃で21hr真空乾燥したMS−4A粉末10ｇ
に、AgOSO2CF33.4ｇ（13.2mmol）と１，２
−ジクロロエタン40mlを加え、系内をアルゴン
置換した。次に、１，２−ジクロルエタン20ml
に溶解した受容体（24）1.6ｇ（3.0mmol）を
加えて、−20℃まで冷却した。そして、１，２
−ジクロルエタン50mlに溶解した供与体（25）
3.5ｇ（4.4mmol）を滴下した。反応は−20℃
→R.T.で17hr行なつた。反応終了後、
CH2Cl2500mlを加えてセライト過し、水洗、
重曹処理をして有機層をMgSO4乾燥した。
過後、減圧濃縮して、その残渣をシリカゲル
300ｇのカラム（展開溶媒トルエン／酢エチ＝
３／１）に通して精製し、シロツプ状の化合物
（26）を3.45ｇ得た（収率93.2％：化合物（24）
から）。
〔化合物（26）の性質〕
TLC Rf＝0.39（トルエン／酢エチ＝２／１）
Anal.Calcd.（％）C66H71NO23.3/4C6H5CH3：
Ｃ，65.06；Ｈ，5.90；Ｎ，1.06
Found（％）：Ｃ，65.15；Ｈ，5.95；Ｎ，1.06
〔α〕23.5 D＋4.2゜（C1.03，CHCl3）
(b) 化合物（26）2.2ｇをMeOH40mlに溶解し、
1N−NaOMe1mlを加えて、室温で22hr撹拌し
た。この反応液を減圧濃縮して、残渣を
MeOH100mlに溶解し、ｎ−BuNH220mlを加
えて、浴温100℃で45hr還流した。この反応液
を減圧濃縮して、残渣をピリジン30mlに溶解
し、Ac2O30mlを加えて、室温で18hr撹拌した。
そして、反応液を減圧濃縮して、その残渣をシ
リカゲル200ｇのカラム（展開溶媒トルエン／
酢エチ＝１／１）に通して精製し、シロツプ状
の化合物（29）を1.9ｇ得た（収率95.0％）。
〔化合物（29）の性質〕
TLC Rf＝0.54（CH2Cl2／アセトン＝５／１）
Anal Calcd.（％）C60H71NO22：
Ｃ，62.22；Ｈ，6.18；Ｎ，1.21
Found（％）：Ｃ，62.57；Ｈ，6.31；Ｎ，1.50
〔α〕21 D＋6.5゜（C1.15，CHCl3）
(c) 化合物（29）123.0mgをAcOH5mlに溶解し、
10％Pd−C0.1ｇを加えてH2を封入し、80℃で
20min撹拌した。セライト過後、減圧濃縮し
て、残渣をピリジン２mlに溶解し、Ac2O2mlを
加えて、室温で20hr撹拌した。そして反応液を
減圧濃縮して、その残渣をシリカゲル６ｇのカ
ラム（展開溶媒 トルエン／酢エチ＝１／５）
に通して精製し、シロツプ状の化合物（31）を
84.5mg得た（収率82.4％）。
〔化合物（31）の性質〕
TLC Rf＝0.41（CH2Cl2／アセトン＝３／１）
Anal.Calcd.（％）C40H55NO26.1/2C6H5CH3：
Ｃ，51.63；Ｈ，5.88；Ｎ，1.38
Found（％）：Ｃ，51.43；Ｈ，5.96；Ｎ，1.78
〔α〕20 D−9.6゜（C0.52，CHCl3）
CMR δC：100.98（Ｃ−1c，1JCH161.1Hz）、100.30
（ｃ−1b、1JCH158.7Hz）、90.99（Ｃ−1a、
1JCH175.8Hz）
(d) 化合物（31）62.8mg（0.065mmol）を
CH2Cl22mlに溶解し、30％HBr−AcOH0.1ml
を加えて、室温で2hr撹拌した。この反応液を
浴温40℃で減圧濃縮し、さらにトルエンと共沸
させて、シロツプ状の化合物(3)を得た。このシ
ロツプ状を精製することなしに次の反応に用い
た。
〔化合物(3)の性質〕
TLC Cf＝0.51（CH2Cl2／アセトン＝３／１）
PMR δ（Ｈ−1a）6.56ppm
実施例 １
(a) 190℃で22hr真空乾燥したMS−4A粉末0.2ｇ
の系内をアルゴン置換し、1.2−ジクロルエタ
ン0.5mlとトルエン0.5mlに溶解した
AgOSO2CF351.4mg（0.20mmol）を加え、さら
に、１，２−ジクロルエタン0.5mlに溶解した
受容体(2)13.7mg（0.011mmol）を加えて、０℃
で撹拌した。そして、１，２−ジクロルエタン
0.5mlに溶解した供与体(3)（0.065mmol相当）
を滴下した。反応は０℃→R.T.で17hr行なつ
た。反応終了後、CH2Cl250mlを加えてセライ
ト過し、水洗、重曹処理をして有機層を
MgSO4乾燥した。過後、減圧濃縮して、そ
の残渣をゲル過（TOYOPEARL HW−40F
200ml、CHCl3／MeOH＝１／１）により精製
し、シロツプ状の化合物（1a）を19.9mg得た
（化合物(2)からの収率58.4％）。
〔化合物（1a）の性質〕
TLC Rf＝0.63（CH2Cl2／アセトン＝１／１）
(b) 化合物（1a）18.7mgをMeOH2mlに溶解し、
1N−NaOMe0.1mlを加えて、室温で21hr撹拌
した。この反応液にAMBERLITECG−
50TyPE2を0.4ml加えて20min撹拌して中和し、
セライト過後、減圧濃縮した。残渣を
AcOH4mlに溶解し、10％Pd−C34mgを加えて
H2を封入し、80℃で20min撹拌した。セライ
ト過後、減圧濃縮して、残渣を80％aq.
AcOH2.5mlに溶解し、10％Pd−C22mgを加え
てH2を封入し、80℃で20min撹拌した。セラ
イト過後、減圧濃縮して、その残渣をゲル
過（Sephadex Ｇ−25 20ml、H2C）により精
製し、凍結乾燥して、化合物（1c）の結晶を
8.1mg得た。収率80.2％
〔化合物（1c）の性質〕
TLC Rf＝0.54（MeOH−AcOH−H2O＝10：
１：１）
〔α〕26.5 D＋1.8゜（C0.11、H2O）
PMR 400MHz（D2O、60℃）
δH：5.139（ｓ、Ｈ−1e）、4.926（ｓ、Ｈ−1d）、
4.766（ｓ、Ｈ−1c）、5.201（ｄ、J3.0Hz）、
Ｈ−1aα）、4.713（ｄ、J7.8Hz、Ｈ−
1aβ）、4.625（ｄ、J8.0Hz、Ｈ−1b）、
4.592（ｄ、J8.8Hz、Ｈ−1f、Ｈ−1g）、
4.478（ｄ、J7.6Hz、Ｈ−1h、Ｈ−1i）、
4.263（bs、Ｈ−2c）、4.200（bs、Ｈ−
2e）、4.120（bs、Ｈ−2d）。
実施例 ２
実施例１(a)において、３糖受容体として化合物
(2)代りに化合物(18)を用いたほかは、同様の操作を
繰り返し、化合物（1d）を得た（収率59％）。
〔化合物（1d）の性質〕
TLC Rf＝0.40（CH2Cl2：アセトン＝３／１）
〔α〕21.5 D−7.6゜（C0.55、CHCl3）
TLC Rf=0.64 (toluene/ethyl acetate=10/1) (k) 12 g of Ag-silicate and 10 g of MS-5A powder were mixed and vacuum-dried at 190° C. for 19 hours. After cooling,
1,2-dichloroethane 80ml after replacing with argon
was added, and further 2.9 g (2.8 mmol) of receptor (16) dissolved in 20 ml of 1,2-dichloroethane was added, followed by stirring at room temperature for 1 hour. Next, cool on ice and 1,2-
Donor (16) dissolved in 20 ml of dichloroethane
(equivalent to 11.2 mmol) was added, and the mixture was stirred at 0°C→RT/16 hours. After the reaction was completed, 500 ml of CH 2 Cl 2 was added, the mixture was filtered through Celite, washed with water, treated with sodium bicarbonate, and the organic layer was dried over MgSO 4 . After filtration, concentrate under reduced pressure.
The residue was purified by passing it through a column of 850 g of silica gel (developing solvent: toluene/ethyl acetate = 10/1) to obtain 1.62 g (39.8%) of β-anomer (17) and 1.45 g (35.6%) of α-anomer (19). were obtained in syrup. β-anomer (17) α-anomer (19) TLC Rf (Toluene/ethyl acetate = 5/1)
0.47 0.53 Anal.Calcd.(%) C 89 H 88 N 2 O 18 : C, 72.54 72.61 72.87 H, 6.02 6.15 6.06 N, 1.90 1.75 1.82 [α] 27.5 D (CHCl 3 ) −2.1゜ +1 5.6゜ ( C1.02) (C1.17) CMRδ C : β-anomer (17) 97.03 (C-1a, C-1b, 1 J CH 164.8Hz) 101.47 (C-1c, 1 J CH 156.3Hz) α-anomer ( 19)96.74 (C-1a or C-1b,
1 J CH 164.8Hz) 97.13 (C-1a or C-1b, 1 J CH 164.8Hz) 100.11 (C-1c, 1 J CH 169.7Hz) (l) Compound (17) 1369.0 mg (0.93 mmol) at 95% aq.
362.4 mg of PdCl2 dissolved in 30 ml of AcOH
(2.04mmol) and AcONa365.8mg (4.46mmol)
was added and stirred at 70°C for 1 hour. Then, the reaction solution was concentrated under reduced pressure, the residue was dissolved in 100 ml of ethyl acetate, saturated aqueous sodium bicarbonate was added, the mixture was filtered through Celite, the layers were separated, and the organic layer was dried with MgSO 4 . After filtration, it was concentrated under reduced pressure, and the residue was purified by passing it through a 140 g column of silica gel (developing solvent: toluene/ethyl acetate = 4/1) to obtain 747.8 mg of syrup-like compound (18).
(yield 57.7%). [Properties of compound (18)] TLC Rf = 0.55 (Toluene/ethyl acetate = 2/1) Anal. Calcd. (%) C 83 H 80 N 2 O 18 : C, 71.53; H, 5.79; N, 2.01 Found (%); C, 71.87; H, 5.91; N, 1.88 [α] 27 D −4.5° (C1.38, CHCl 3 ) (m) In a flask containing 150 mg (0.108 mmol) of compound (18) Add MeOH5c.c. and BuNH 2 5c.c. at 50℃.
The mixture was heated and stirred overnight. Thereafter, the bath temperature was raised to reflux temperature (90°C to 100°C), and the mixture was heated and stirred for 7 days. During this period, MeOH:BuNH 2 =1:
4 c.c. of solution of 1 was added. The reaction solution was concentrated under reduced pressure until the amine odor disappeared. The residue was dissolved in pyridine 2c.c.Ac 2 O2c.c. and left stirring at room temperature overnight. The reaction solution was azeotroped with EtOH and concentrated under reduced pressure, and the residue was subjected to column chromatography using 5.0 g of SiO 2 CH 2 Cl 2 :acetone=5:1 to obtain 200 mg of SiO 2 containing various target products. (Rf
=0.74, CH 2 Cl 2 :acetone = 5:1) The above classification is MeOH4c.c., 1NNaOMe/MeOH
Deacetylation is carried out with 20 drops of solution. The reaction solution was stirred overnight at room temperature, neutralized with Amberlyst A-15, filtered and concentrated under reduced pressure, and the residue was dissolved in 10 g of SiO 2
Silica gel chromatography was performed using CH 2 Cl 2 :acetone=10:1 to obtain 117 mg of compound (2). [Properties of compound (2)] TLC Rf = 0.47 (CH 2 Cl 2 / acetone = 3/1) Anal. Calcd. (%) C 71 H 80 N 2 O 16・H 2 O: C,
69.02 ; H, 6.69; N, 2.27 Found (%); C , 69.08; , 1 J CH 156.3Hz) 99.86 (C-1ab, 1 J CH 162.4Hz) Reference example 2 Synthesis of trisaccharide donor (a) 10 g of MS-4A powder vacuum dried at 190°C for 21 hours
3.4 g (13.2 mmol) of AgOSO 2 CF 3 and 1,2
-40 ml of dichloroethane was added, and the system was purged with argon. Next, 20ml of 1,2-dichloroethane
1.6 g (3.0 mmol) of receptor (24) dissolved in was added, and the mixture was cooled to -20°C. And 1, 2
- Donor (25) dissolved in 50 ml of dichloroethane
3.5 g (4.4 mmol) was added dropwise. Reaction at -20℃
→I spent 17 hours on RT. After the reaction is complete,
Add 500ml of CH 2 Cl 2 and filter through Celite, wash with water,
After treatment with baking soda, the organic layer was dried over MgSO4 .
After filtration, concentrate under reduced pressure and transfer the residue to silica gel.
300g column (developing solvent toluene/ethyl acetate =
3/1) to obtain 3.45g of syrupy compound (26) (yield 93.2%: compound (24)
from). [Properties of compound (26)] TLC Rf = 0.39 (toluene/ethyl acetate = 2/1) Anal.Calcd. (%) C 66 H 71 NO 23 .3/4C 6 H 5 CH 3 : C, 65.06; H , 5.90; N, 1.06 Found (%): C, 65.15; H, 5.95; N, 1.06 [α] 23.5 D +4.2° (C1.03, CHCl 3 ) (b) Add 2.2 g of compound (26) to 40 ml of MeOH dissolved in
1 ml of 1N-NaOMe was added, and the mixture was stirred at room temperature for 22 hours. This reaction solution was concentrated under reduced pressure to remove the residue.
It was dissolved in 100 ml of MeOH, 20 ml of n-BuNH 2 was added, and the mixture was refluxed for 45 hours at a bath temperature of 100°C. The reaction solution was concentrated under reduced pressure, the residue was dissolved in 30 ml of pyridine, 30 ml of Ac 2 O was added, and the mixture was stirred at room temperature for 18 hours.
Then, the reaction solution was concentrated under reduced pressure, and the residue was transferred to a column of 200 g of silica gel (developing solvent: toluene/
The mixture was purified by passing it through ethyl acetate (1/1) to obtain 1.9 g of syrupy compound (29) (yield 95.0%). [Properties of compound (29)] TLC Rf = 0.54 (CH 2 Cl 2 / acetone = 5/1) Anal Calcd. (%) C 60 H 71 NO 22 : C, 62.22; H, 6.18; N, 1.21 Found ( %): C, 62.57; H, 6.31; N, 1.50 [α] 21 D +6.5° (C1.15, CHCl 3 ) (c) 123.0 mg of compound (29) was dissolved in 5 ml of AcOH,
Add 0.1g of 10% Pd-C, seal in H2 , and heat at 80℃.
Stirred for 20 min. After filtering through Celite, the mixture was concentrated under reduced pressure, the residue was dissolved in 2 ml of pyridine, 2 ml of Ac 2 O was added, and the mixture was stirred at room temperature for 20 hours. Then, the reaction solution was concentrated under reduced pressure, and the residue was applied to a column of 6 g of silica gel (developing solvent: toluene/ethyl acetate = 1/5).
to obtain a syrupy compound (31).
84.5 mg was obtained (yield 82.4%). [Properties of compound (31)] TLC Rf = 0.41 (CH 2 Cl 2 / acetone = 3/1) Anal. Calcd. (%) C 40 H 55 NO 26 .1/2C 6 H 5 CH 3 : C, 51.63 ; H, 5.88; N, 1.38 Found (%): C , 51.43 ; 1 J CH 161.1Hz), 100.30
(c-1b, 1 J CH 158.7Hz), 90.99 (C-1a,
1 J CH 175.8Hz) (d) 62.8mg (0.065mmol) of compound (31)
Dissolved in 2ml of CH2Cl2 , 0.1ml of 30% HBr−AcOH
was added and stirred at room temperature for 2 hours. This reaction solution was concentrated under reduced pressure at a bath temperature of 40°C, and further azeotroped with toluene to obtain a syrupy compound (3). This syrup was used in the next reaction without purification. [Properties of compound (3)] TLC Cf = 0.51 (CH 2 Cl 2 /acetone = 3/1) PMR δ (H-1a) 6.56 ppm Example 1 (a) MS-4A powder vacuum dried at 190°C for 22 hours 0.2g
The system was replaced with argon and dissolved in 0.5 ml of 1,2-dichloroethane and 0.5 ml of toluene.
Add 51.4 mg (0.20 mmol) of AgOSO 2 CF 3 and further add 13.7 mg (0.011 mmol) of receptor (2) dissolved in 0.5 ml of 1,2-dichloroethane.
It was stirred with and 1,2-dichloroethane
Donor (3) dissolved in 0.5ml (equivalent to 0.065mmol)
was dripped. The reaction was carried out at 0°C→RT for 17 hours. After the reaction is complete, add 50ml of CH 2 Cl 2 and filter through Celite, wash with water, and treat with baking soda to remove the organic layer.
Dry MgSO4 . After filtration, the residue was concentrated under reduced pressure and subjected to gel filtration (TOYOPEARL HW-40F
200 ml, CHCl 3 /MeOH=1/1) to obtain 19.9 mg of syrupy compound (1a) (yield 58.4% from compound (2)). [Properties of compound (1a)] TLC Rf = 0.63 (CH 2 Cl 2 / acetone = 1/1) (b) 18.7 mg of compound (1a) was dissolved in 2 ml of MeOH,
0.1 ml of 1N-NaOMe was added, and the mixture was stirred at room temperature for 21 hours. Add AMBERLITECG- to this reaction solution.
Add 0.4ml of 50TyPE2 and stir for 20min to neutralize.
After passing through Celite, the mixture was concentrated under reduced pressure. residue
Dissolve in 4ml of AcOH and add 34mg of 10% Pd-C.
The mixture was filled with H 2 and stirred at 80° C. for 20 min. After filtering through Celite, the residue was concentrated under reduced pressure to 80% aq.
It was dissolved in 2.5 ml of AcOH, 22 mg of 10% Pd-C was added, H 2 was enclosed, and the mixture was stirred at 80°C for 20 min. After filtering through Celite, it was concentrated under reduced pressure, and the residue was purified by gel filtration (Sephadex G-25 20ml, H 2 C) and freeze-dried to obtain crystals of compound (1c).
Obtained 8.1 mg. Yield 80.2% [Properties of compound (1c)] TLC Rf=0.54 (MeOH-AcOH- H2O =10:
1:1) [α] 26.5 D +1.8゜ (C0.11, H 2 O) PMR 400MHz (D 2 O, 60℃) δ H : 5.139 (s, H-1e), 4.926 (s, H- 1d),
4.766 (s, H-1c), 5.201 (d, J3.0Hz),
H-1aα), 4.713 (d, J7.8Hz, H-
1aβ), 4.625 (d, J8.0Hz, H-1b),
4.592 (d, J8.8Hz, H-1f, H-1g),
4.478 (d, J7.6Hz, H-1h, H-1i),
4.263 (bs, H-2c), 4.200 (bs, H-
2e), 4.120 (bs, H-2d). Example 2 In Example 1(a), the compound
Compound (1d) was obtained by repeating the same procedure except that compound (18) was used instead of (2) (yield 59%). [Properties of compound (1d)] TLC Rf=0.40 (CH 2 Cl 2 : Acetone = 3/1) [α] 21.5 D −7.6° (C0.55, CHCl 3 )
Claims (1)
たはアセチル基、R2は水素原子またはベンジル
基、R3は水素原子、R4は水素原子またはアセチ
ル基を示し、またR3とR4は共同してフタロイル
基を形成してもよい。 ２ 式 （式中、Acはアセチル基、Ｘはハロゲン原子
を示す） で表わされる化合物と、式 （式中、Bnはベンジル基、R3は水素原子、R4
はアセチル基を示し、またR3とR4は共同してフ
タロイル基を形成してもよい） で表わされる化合物を反応させ、必要により脱ア
セチル化、脱ベンジル化、脱フタロイル化および
アセチル化することを特徴とする下記の一般式で
表わされる複合多糖の製造法。 上記式中、Acはアセチル基、R1は水素原子ま
たはアセチル基、R2は水素原子またはベンジル
基、R3は水素原子、R4は水素原子またはアセチ
ル基を示し、またR3とR4は共同してフタロイル
基を形成してもよい。[Claims] 1. A complex polysaccharide represented by the following general formula. In the above formula, Ac is an acetyl group, R 1 is a hydrogen atom or an acetyl group, R 2 is a hydrogen atom or a benzyl group, R 3 is a hydrogen atom, R 4 is a hydrogen atom or an acetyl group, and R 3 and R 4 may jointly form a phthaloyl group. 2 formulas (In the formula, Ac is an acetyl group and X is a halogen atom.) (In the formula, Bn is a benzyl group, R 3 is a hydrogen atom, R 4
represents an acetyl group, and R 3 and R 4 may jointly form a phthaloyl group), and if necessary, deacetylate, debenzylate, dephthaloylate, and acetylate. A method for producing a complex polysaccharide represented by the following general formula, characterized by: In the above formula, Ac is an acetyl group, R 1 is a hydrogen atom or an acetyl group, R 2 is a hydrogen atom or a benzyl group, R 3 is a hydrogen atom, R 4 is a hydrogen atom or an acetyl group, and R 3 and R 4 may jointly form a phthaloyl group.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15882383A JPS6051702A (en) | 1983-08-30 | 1983-08-30 | Conjugated polysaccharide and its production |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15882383A JPS6051702A (en) | 1983-08-30 | 1983-08-30 | Conjugated polysaccharide and its production |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6051702A JPS6051702A (en) | 1985-03-23 |
| JPH0536441B2 true JPH0536441B2 (en) | 1993-05-31 |
Family
ID=15680154
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15882383A Granted JPS6051702A (en) | 1983-08-30 | 1983-08-30 | Conjugated polysaccharide and its production |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6051702A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL135148A0 (en) | 1997-10-03 | 2001-05-20 | Galenica Pharmaceuticals Inc | A polysaccharide conjugate and pharmaceutical compositions containing the same |
| EP1574217A1 (en) * | 1997-10-03 | 2005-09-14 | Galenica Pharmaceuticals, Inc. | Imine-forming polysaccharides, preparation thereof and the use thereof as adjuvants and immunostimulants |
-
1983
- 1983-08-30 JP JP15882383A patent/JPS6051702A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6051702A (en) | 1985-03-23 |
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