JPS6344589A - Sialic acid derivative and production thereof - Google Patents
Sialic acid derivative and production thereofInfo
- Publication number
- JPS6344589A JPS6344589A JP18798286A JP18798286A JPS6344589A JP S6344589 A JPS6344589 A JP S6344589A JP 18798286 A JP18798286 A JP 18798286A JP 18798286 A JP18798286 A JP 18798286A JP S6344589 A JPS6344589 A JP S6344589A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- formulas
- added
- sialic acid
- 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
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical class CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 38
- 238000000034 method Methods 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 2
- 230000021736 acetylation Effects 0.000 claims 1
- 238000006640 acetylation reaction Methods 0.000 claims 1
- 150000002270 gangliosides Chemical class 0.000 abstract description 9
- 238000006243 chemical reaction Methods 0.000 abstract description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 abstract description 5
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 abstract description 3
- 238000002425 crystallisation Methods 0.000 abstract description 2
- 230000008025 crystallization Effects 0.000 abstract description 2
- -1 ganglioside GQ1b Chemical class 0.000 abstract description 2
- 238000001953 recrystallisation Methods 0.000 abstract description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 abstract 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 abstract 3
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 abstract 1
- 239000000706 filtrate Substances 0.000 abstract 1
- 239000003456 ion exchange resin Substances 0.000 abstract 1
- 229920003303 ion-exchange polymer Polymers 0.000 abstract 1
- 229960004592 isopropanol Drugs 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- BKZQMWNJESHHSA-PQYSTZNASA-N methyl N-acetylneuraminate Chemical compound COC(=O)C1(O)C[C@H](O)[C@@H](NC(C)=O)[C@H]([C@H](O)[C@H](O)CO)O1 BKZQMWNJESHHSA-PQYSTZNASA-N 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 7
- SQVRNKJHWKZAKO-PFQGKNLYSA-N N-acetyl-beta-neuraminic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-PFQGKNLYSA-N 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102000015336 Nerve Growth Factor Human genes 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- 230000000397 acetylating effect Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229940053128 nerve growth factor Drugs 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 description 1
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 1
- 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 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 1
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
- 239000012345 acetylating agent Substances 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 230000011748 cell maturation Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000002339 glycosphingolipids Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002632 lipids Chemical group 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000002052 molecular layer Substances 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
- 150000002482 oligosaccharides Polymers 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 125000005629 sialic acid group Chemical group 0.000 description 1
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、例えばガングリオシドＧ Ｑ １ｂやＧＱ、
ｃなどのガングリオシドの合成中間体として有用なシア
ル酸誘導体及びその製造方法に関する。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to ganglioside G Q 1b, GQ,
The present invention relates to sialic acid derivatives useful as intermediates for the synthesis of gangliosides such as c, and methods for producing the same.
浦乳動物細胞の糖脂質（グリコリピド）は、スフィンゴ
シンという長鎖アミノアルコールに脂肪酸がアミド結合
したセラミドという脂質構造に、グルコース、ガラクト
ース、Ｎ−アセチルグルコサミン、Ｎ−アセチルガラク
トサミン、フコース、シアル酸などの糖が種々の組み合
せでグリコシド結合したもので、いわゆるスフィンゴ糖
脂質といわれる範ちゅうに属するものである。これらの
うち、シアル酸を有するものを特にガングリオシドと呼
んでいる。Glycolipids in mammalian cells contain a lipid structure called ceramide, which is an amide bond of a fatty acid to a long-chain amino alcohol called sphingosine, and contains glucose, galactose, N-acetylglucosamine, N-acetylgalactosamine, fucose, sialic acid, etc. They are composed of various combinations of sugars linked to glycosidic bonds and belong to the so-called glycosphingolipids. Among these, those having sialic acid are particularly called gangliosides.
これらの化合物は、一般にその大部分が細胞膜２分子層
の外側分子層に局在し、最近の研究によれば、細胞にお
ける識別や情報の受容と応答、レセプター機能分化、細
胞の増殖、悪性変化、行動などにおいて重要な役割を果
たしているものと考えられている。Most of these compounds are generally localized in the outer molecular layer of the two molecular layers of the cell membrane, and according to recent studies, they play a role in cell identification, information reception and response, receptor functional differentiation, cell proliferation, and malignant changes. It is thought that it plays an important role in behavior, etc.
ガングリオシドには種々のものが知られており、その中
にはＮ−アセチルノイラミン酸（Ｎｅｕ Ｎへ〇）がα
（２−８）結合で二量化しているガングリオシドＧ Ｑ
＋ ｂやＧＱ、ｃが知られている。特に、ガングリオ
シドＧＱ、、は最近、２種の神経芽腫細胞系、ＧＯＴＯ
及びＮＢ−１において新規な神経成長因子（ＮＧＦ）様
活性を示すことが発見され、その生′物活性が注目され
ている。Various gangliosides are known, among which N-acetylneuraminic acid (Neu N)
(2-8) Ganglioside G Q dimerized by bond
+ b, GQ, and c are known. In particular, ganglioside GQ, has recently been studied in two neuroblastoma cell lines, GOTO
It has been discovered that NB-1 and NB-1 exhibit novel nerve growth factor (NGF)-like activity, and their biological activities are attracting attention.
しかしながら、シアル酸を含むオリゴ＠鎖を生物体から
単離精製することは極めて困難である。However, it is extremely difficult to isolate and purify oligo@chains containing sialic acid from living organisms.
従って、このようなシアル酸含有オリゴ糖鎖の精密合成
は、これら糖類の正確な生物情報と、分子構造とのｔ目
間を解明するうえで、必要不可欠なことであった。Therefore, precise synthesis of such sialic acid-containing oligosaccharide chains is essential for elucidating accurate biological information and molecular structures of these saccharides.
本発明の目的は、ガングリオシドの合成中間体として有
用な新規なシアル酸誘導体、およびそれらの製造方法を
提供することにある。An object of the present invention is to provide novel sialic acid derivatives useful as ganglioside synthesis intermediates and methods for producing them.
本発明の新規なシアル酸誘導体は、−最大：（ただし、
Ａｃ ＝Ｃ０Ｃ）１３ 、及びＭｅ ＝ＣＬ ）で示さ
れる化合物及び−最大：
（ただし、Ｒ＝Ｃ［ＩＣ，Ｈ，又はＨＳＡｃ ＝ＣＯＣ
Ｈ３、及びＭｅ ＝ＣＨ＊ ）
で示される化合物であり、
また、本発明の新規な製造方法は、式（■）：〔ただし
、Ａｃ ＝ＣＯＣＨ３、Ｍｅ ＝Ｃ）＋３ 、及びＢｚ
１ ＝ＣＯＣＨ３（以下同様）〕で示される化合物（
Ｖ）を製造する方法であって、（ａ）式（■）：
Ａｅ
で示される化合物（ｎ）をアセチル化して、式（■）：
Ｐ
で示される化合物（Ｉ［Ｉ）を得、
ら）前記化合物（Ｉ［Ｉ）からそのプロピリデン保護基
を脱離化して、
式（■）：
Ｈ
で示される化合物（ｒＶ）を得、
（Ｃ） 前記化合物（ＴＶ）をベンゾイル化する、こ
とを含む方法である。The novel sialic acid derivatives of the present invention are characterized in that - up to:
Ac = C0C) 13 , and Me = CL
H3, and Me=CH*), and the novel production method of the present invention is a compound represented by the formula (■): [where Ac=COCH3, Me=C)+3, and Bz
1 = COCH3 (the same applies hereinafter)]
(a) acetylating a compound (n) represented by formula (■): Ae to obtain a compound (I[I) represented by formula (■): P; ) removing the propylidene protecting group from the compound (I[I) to obtain a compound (rV) represented by the formula (■): H; (C) benzoylating the compound (TV); This is a method that includes
以下、本発明について詳述する。The present invention will be explained in detail below.
上記化合物（Ｉ［）は、式（■）：
Ｏ
叶
で示されるＮ−アセチルノイラミン酸のメチルエステル
を、ｐ−）ルエンスルホン酸（ｐ −ＴｓＯＨ）などの
触媒の存在下、アセトンなどの溶媒中で、ジメトキシプ
ロパンで処理して得ることができる。The above compound (I[) is prepared by converting the methyl ester of N-acetylneuraminic acid represented by the formula (■): It can be obtained by treatment with dimethoxypropane in a solvent.
尚、化合物（Ｉ）は市場で容易に人手できるか、Ｎ−ア
セチルノイラミン酸を公知の方法でメチルエステル化し
て容易に得ることができる。Compound (I) can be easily obtained manually on the market or by methyl esterifying N-acetylneuraminic acid by a known method.
化合物（ＩＩＩ）は、化合物（ＩＩ）をアセチル化して
得られるが、このアセチル化剤としては例えば無水酢酸
が挙げられる。反応は、ピリジンなどの溶媒中で、一般
に０〜１００℃、好ましくは室温（２０〜２５℃）付近
において、一般に１０分〜１０時間行なわれる。Compound (III) is obtained by acetylating compound (II), and examples of the acetylating agent include acetic anhydride. The reaction is generally carried out in a solvent such as pyridine at 0 to 100°C, preferably around room temperature (20 to 25°C) for 10 minutes to 10 hours.
化合物（ｒＶ）は化合物（ＩＩＩ）の保護基脱離化によ
り得られる。この反応は酢酸などの作用により、例えば
０〜１００℃、好ましくは２０〜８０℃において、一般
に１０分〜８時間行なう。Compound (rV) can be obtained by removing the protecting group of compound (III). This reaction is generally carried out for 10 minutes to 8 hours at, for example, 0 to 100°C, preferably 20 to 80°C, by the action of acetic acid or the like.
化合Ｐ７１（Ｖ）は、化合物（ＩＶ）をベンゾイル化す
ることにより得られる。ベンゾイル化剤として塩化ベン
ゾイルなどが挙げられる。溶媒としては、ＣＨ２Ｃｊ！
、、ピリジンなどが使用される。Compound P71 (V) can be obtained by benzoylating compound (IV). Examples of the benzoylating agent include benzoyl chloride. As a solvent, CH2Cj!
,, pyridine, etc. are used.
こ有用性〕
本発明の新規化合物は、今まで合成が困難とされていた
シアル酸の８位に各種Ｗ換基を有するシアル酸誘導体の
合成中間体として非常に有用である。Usefulness] The novel compound of the present invention is very useful as an intermediate for the synthesis of sialic acid derivatives having various W substituents at the 8-position of sialic acid, which have been difficult to synthesize until now.
以下、実施例により本発明を更に詳述する。 Hereinafter, the present invention will be explained in further detail with reference to Examples.
実施例１
化合物（ｎ）の合成
Ｎ−アセチルノイラミン酸（Ｎｅｕ ５Ａｃ ）メチル
エステル５ｇのアセトン１０〇−溶液にジメトキシプロ
パン８ｇ及びｐ −ＴｓＯｔｌ １０ ｍｇを加え室温
で３０分間攪拌後Ｄｏｗｅｘ −１（ＤＨ−） １
ｇを加えｐ−Ｔｓ叶を中和した。反応液を口過し、四肢
を減圧下で乾固し２−プロパツールから結晶化及び再結
晶を行ない無色針状晶４．５６ｇ（収率８１％）で化合
物（ｎ）を得た。Example 1 Synthesis of Compound (n) 8 g of dimethoxypropane and 10 mg of p-TsOtl were added to a solution of 5 g of N-acetylneuraminic acid (Neu 5Ac) methyl ester in 100 mg of acetone, and after stirring at room temperature for 30 minutes, Dowex-1 ( DH-) 1
g was added to neutralize the p-Ts leaves. The reaction solution was passed through the mouth, the extremities were dried under reduced pressure, and crystallization and recrystallization from 2-propatol were performed to obtain 4.56 g (yield: 81%) of compound (n) as colorless needles.
ｍａ×
’ＨＮＭＲ（ＣＤＣｊ２１ ） δ、（ＴＭＳ＞２、
０８ （３Ｈ，ｓ、 ＮＡｃ ）
２．０８ （ＩＨ，ｄｄ、 Ｊ ＝１３．Ｏ，１１，０
Ｈｚ、 ３−Ｈａｘ ）２．２４ （ＬＨ，ｄｄ、 Ｊ
＝１３．０ ．５．０ Ｈｚ、 ３−）１ｅｑ ）実
施例２
化合物（Ｉ）の合成
化合物（ＩＩ）４．５６ｇに無水酢酸１５ｍｆとピリジ
ン１５ｍｊ！を加え室温で一夜放置後、ＥｔＯＨを加え
過剰な無水酢酸を分解し、反応後の溶媒を減圧下留去し
て淡黄色の油状物を得た。これをエタノールから結晶化
及び再結晶を行なうと無色針状晶として化合物（Ｉ［）
を３．５１ｇ（収率５７％）で得た。max 'HNMR (CDCj21) δ, (TMS>2,
08 (3H, s, NAc) 2.08 (IH, dd, J = 13.O, 11,0
Hz, 3-Hax)2.24 (LH, dd, J
=13.0. 5.0 Hz, 3-)1 eq) Example 2 Synthesis of compound (I) 4.56 g of compound (II), 15 mf of acetic anhydride and 15 mj of pyridine! was added and allowed to stand overnight at room temperature, then EtOH was added to decompose excess acetic anhydride, and the solvent after the reaction was distilled off under reduced pressure to obtain a pale yellow oil. When this is crystallized and recrystallized from ethanol, the compound (I[)
was obtained in an amount of 3.51 g (yield 57%).
ｍｐ ２０４−２０６℃、〔α〕、−５２°（Ｃ＝ １
、ＭｅＯＨ）ＮＭＲデータを下記の表−１に示す。mp 204-206℃, [α], -52° (C=1
, MeOH) NMR data are shown in Table 1 below.
実施例２
化合物（］の合成
化合物（！ＩＩ）２．５ｇを８０％酢酸−水に溶かし、
６０℃、２時間加温後、溶媒を留去しエタノールから結
晶化及び再結晶化し無色針状晶として化合物（ｒＶ）を
１．５ｇ（収率６５１％）で得た。Example 2 Synthesis of compound () 2.5 g of compound (!II) was dissolved in 80% acetic acid-water,
After heating at 60°C for 2 hours, the solvent was distilled off, and the mixture was crystallized and recrystallized from ethanol to obtain 1.5 g (yield: 651%) of compound (rV) as colorless needle crystals.
ｍｐ ２０９−２１０℃、（（２）ａ、 ４５°（Ｃ
＝ １ 、ＭｅＯＨ）この化合物（ｒＶ）のＮＭＲデー
タを表−１に示す。mp 209-210℃, ((2)a, 45°(C
= 1, MeOH) NMR data of this compound (rV) are shown in Table-1.
実施例３
化合物（Ｖ）の合成
化合物（ＩＶ）１．５ｇをＣＨ，Ｃｆ ２に溶かしアル
ゴン気流中−１５℃に冷却しピリジン５ｍｌを加え攪拌
しながら塩化ベンゾイル６．３ｇを滴下した。塩化ベン
ゾイルの滴下はＴ Ｌ Ｃ（！、Ｉｅｒｋ、 Ｋｉｅｓ
ｅ１ｇｅ１６０Ｆ２Ｓ４）展開溶媒ＣＨＣｊＬ ：！
ＪｅＯＨ（１０： ｌ ）化合物（ｒＶ） ： Ｒｆ
＝０．２２、化合物（■）：Ｒｆ＝０．４８を確言忍し
ながらおこなった。Example 3 Synthesis of Compound (V) 1.5 g of Compound (IV) was dissolved in CH, Cf 2 and cooled to −15° C. in an argon stream. 5 ml of pyridine was added thereto, and 6.3 g of benzoyl chloride was added dropwise with stirring. Dropwise addition of benzoyl chloride is performed using TLC (!, Ierk, Kies
e1ge160F2S4) Developing solvent CHCjL:!
JeOH (10: l) compound (rV): Rf
= 0.22, Compound (■): Rf = 0.48.
原料のスポットが消失後、反応液に水３０ｄを加え、ク
ロロホルム２０ｍ／！で２回抽出した。抽出液は５％炭
酸す） ＩＪウム水、水、で処理後、無水硫酸す） ＋
Ｊウムで乾燥、口過し、溶媒を留去した。After the spots of raw materials disappeared, 30 d of water was added to the reaction solution, and 20 m/! of chloroform was added. Extracted twice. The extract is treated with 5% carbonic acid), IJum water, and water, then treated with anhydrous sulfuric acid) +
The mixture was dried over Jumbo, filtered, and the solvent was distilled off.
残った油状物をＥｔＯＨ−エーテルの混合溶媒を用い結
晶化及び再結晶化すると無色針状晶として化合物（Ｖ）
をＩｇ（収率５４％）で１等だ。The remaining oil was crystallized and recrystallized using a mixed solvent of EtOH-ether to give compound (V) as colorless needles.
is ranked first in Ig (yield 54%).
ｍｐ １８０−１８３℃、〔α） Ｄ −２０°（Ｃ＝
１ 、ＭｅＯＨ）この化合物（Ｖ）のＮＭＲデータを
表−１に示す。mp 180-183℃, [α) D -20° (C=
1, MeOH) NMR data of this compound (V) are shown in Table-1.
Claims (3)
で示される化合物。(1) General formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (However, Ac=COCH_3 and Me=CH_3)
The compound shown in
Ｈ＿３、及びＭｅ＝ＣＨ＿３） で示される化合物。(2) General formulas: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (However, R=COC_6H_5 or H, Ac=COC
H_3, and Me=CH_3).
Ｂ＿２ｌ＝ＣＯＣ＿６Ｈ＿５（以下同様）〕で示される
化合物（Ｖ）を製造する方法であっ（ａ）式（II）： ▲数式、化学式、表等があります▼（II） で示される化合物（II）をアセチル化して、式（III）
： ▲数式、化学式、表等があります▼（III） で示される化合物（III）を得、 保護基を脱離化して、 式（VI）： ▲数式、化学式、表等があります▼（IV） で示される化合物（IV）を得、 （ｃ）前記化合物（IV）をベンゾイル化する、ことを含
む方法。(3) Formula (V): ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [However, Ac=COCH_3, Me=CH_3, and B_2l=COC_6H_5 (the same applies hereinafter)] A method for producing compound (V) Ah (a) Formula (II): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) Acetylation of compound (II) shown by formula (III)
: ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III) Obtain the compound (III) shown by, remove the protecting group, and get the formula (VI): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(IV) A method comprising: obtaining a compound (IV) represented by: (c) benzoylating the compound (IV).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP18798286A JPS6344589A (en) | 1986-08-11 | 1986-08-11 | Sialic acid derivative and production thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP18798286A JPS6344589A (en) | 1986-08-11 | 1986-08-11 | Sialic acid derivative and production thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS6344589A true JPS6344589A (en) | 1988-02-25 |
Family
ID=16215544
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP18798286A Pending JPS6344589A (en) | 1986-08-11 | 1986-08-11 | Sialic acid derivative and production thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6344589A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5034516A (en) * | 1987-08-04 | 1991-07-23 | University Of Ottawa | Synthetic antigens of sialic acid and derivatives thereof |
| US5177062A (en) * | 1988-08-09 | 1993-01-05 | Mect Corporation | Method for treating immune complex diseases with n-acetylneuraminic acid |
| JPH0683534U (en) * | 1993-05-21 | 1994-11-29 | 謹造 神田 | Attachment for replenishing brake oil |
-
1986
- 1986-08-11 JP JP18798286A patent/JPS6344589A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5034516A (en) * | 1987-08-04 | 1991-07-23 | University Of Ottawa | Synthetic antigens of sialic acid and derivatives thereof |
| US5177062A (en) * | 1988-08-09 | 1993-01-05 | Mect Corporation | Method for treating immune complex diseases with n-acetylneuraminic acid |
| JPH0683534U (en) * | 1993-05-21 | 1994-11-29 | 謹造 神田 | Attachment for replenishing brake oil |
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