JPH01180894A - Novel production of amino sugar derivative - Google Patents
Novel production of amino sugar derivativeInfo
- Publication number
- JPH01180894A JPH01180894A JP170888A JP170888A JPH01180894A JP H01180894 A JPH01180894 A JP H01180894A JP 170888 A JP170888 A JP 170888A JP 170888 A JP170888 A JP 170888A JP H01180894 A JPH01180894 A JP H01180894A
- Authority
- JP
- Japan
- Prior art keywords
- amino sugar
- acid
- formula
- sugar derivative
- represented
- 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
- 150000002336 glycosamine derivatives Chemical class 0.000 title claims description 9
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- 239000002253 acid Substances 0.000 claims abstract description 8
- 125000002252 acyl group Chemical group 0.000 claims abstract description 6
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical class ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 abstract description 21
- 239000002994 raw material Substances 0.000 abstract description 7
- -1 trialkylsilyl ester Chemical class 0.000 abstract description 6
- 150000001875 compounds Chemical class 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 4
- 238000003756 stirring Methods 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract 1
- 239000011369 resultant mixture Substances 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- MSFSPUZXLOGKHJ-UHFFFAOYSA-N Muraminsaeure Natural products OC(=O)C(C)OC1C(N)C(O)OC(CO)C1O MSFSPUZXLOGKHJ-UHFFFAOYSA-N 0.000 description 3
- 108010013639 Peptidoglycan Proteins 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 150000002337 glycosamines Chemical class 0.000 description 3
- 239000000677 immunologic agent Substances 0.000 description 3
- 229940124541 immunological agent Drugs 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- 125000003504 2-oxazolinyl group Chemical group O1C(=NCC1)* 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 229920001222 biopolymer Polymers 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000012454 non-polar solvent Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- MSWZFWKMSRAUBD-QZABAPFNSA-N beta-D-glucosamine Chemical compound N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-QZABAPFNSA-N 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000003415 peat Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- RMSRTQNVIVIPDI-UHFFFAOYSA-N triethylsilyl 1,1,2,2,2-pentafluoroethanesulfonate Chemical compound CC[Si](CC)(CC)OS(=O)(=O)C(F)(F)C(F)(F)F RMSRTQNVIVIPDI-UHFFFAOYSA-N 0.000 description 1
- STMPXDBGVJZCEX-UHFFFAOYSA-N triethylsilyl trifluoromethanesulfonate Chemical compound CC[Si](CC)(CC)OS(=O)(=O)C(F)(F)F STMPXDBGVJZCEX-UHFFFAOYSA-N 0.000 description 1
- SQQPOWPHFZZOEC-UHFFFAOYSA-N trimethylsilyl 1,1,2,2,2-pentafluoroethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)C(F)(F)F SQQPOWPHFZZOEC-UHFFFAOYSA-N 0.000 description 1
- WKHJMDOEXKAHFZ-UHFFFAOYSA-N trimethylsilyl 1,1,2,2,3,3,3-heptafluoropropane-1-sulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)F WKHJMDOEXKAHFZ-UHFFFAOYSA-N 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
［発明の利用分野］
本発明は、医薬品、免疫薬剤等の原料、中間体等として
有用なアミノ糖誘導体の新規な製造法に関する。DETAILED DESCRIPTION OF THE INVENTION [Field of Application of the Invention] The present invention relates to a novel method for producing amino sugar derivatives useful as raw materials, intermediates, etc. for pharmaceuticals, immunological agents, etc.
［発明の背景］
細菌細胞壁の骨格を形成しているペプチドグリカン部（
特にヒトをはじめとする哺乳動物に寄生する細菌のペプ
チドクリカン）に多彩な生物活性（免疫調節作用、発熱
原性等）が存在していることは古くから知られている。[Background of the Invention] Peptidoglycan moieties that form the skeleton of bacterial cell walls (
In particular, it has been known for a long time that the bacterial peptidochrycan that parasitizes humans and other mammals has a variety of biological activities (immunomodulatory effects, pyrogenicity, etc.).
ペプチドグリカンの有する免疫増強活性の最小単位につ
いては１９７４〜１９７５年フランスのＬｅｄｅｒｅｒ
ら、及び大阪大の小春、芝らのグループにより、それ
がＮ−アセチルムラミルーし一アラニルーＤ−イソクル
タミン（ＭＤＰ）であることが明らかにされている。Regarding the smallest unit of immune-enhancing activity possessed by peptidoglycan, Lederer of France in 1974-1975
et al. and Koharu, Shiba et al.'s group at Osaka University revealed that it is N-acetylmuramyl-mono-alanyl-D-isocurtamine (MDP).
一方、クラ４ム陰性菌の細胞壁外膜に局在するリボ多糖
（ＬＰＳ）は内毒素（エンドトキシン）の主成分として
知られ、抗腫瘍活性を含むさまざまな生理活性を有して
いることが同様に知られている。On the other hand, ribopolysaccharide (LPS), which is localized in the outer membrane of the cell wall of Clam-negative bacteria, is known as the main component of endotoxin, and is also known to have various physiological activities including antitumor activity. known to.
このリボ多糖の本体であるリビッドＡについても、西ド
イツのＷｅｓｔｐｈａｌ −派ら、及びＭＩＴのＫｈｏ
ｒａｎａらにより新たな構造式が提案されている。Regarding rib A, which is the main body of ribopolysaccharide, the Westphal school of West Germany and Kho of MIT
A new structural formula has been proposed by Rana et al.
このように、多彩な生物活性を有し、医薬品や免疫薬剤
としての用途が期待できるこれらペプチドクリカンやリ
ボ多糖等の生体高分子に関する基礎研究、並ひにこれら
の活性を有効利用しようとする応用研究か各方面に於い
て活発に進められている現状である。In this way, basic research on biopolymers such as peptide crican and ribopolysaccharide, which have a variety of biological activities and are expected to be used as pharmaceuticals and immunological agents, as well as applications that aim to effectively utilize these activities, is underway. Currently, research is actively progressing in various fields.
これらペプチドグリカンやリボ多糖等の生体高分子に関
する基礎研究に於いては、これらの、或はこれらの原料
となる化合物の化学的合成方法についても精力的に研究
が行われている。In basic research on biopolymers such as peptidoglycan and ribopolysaccharide, chemical synthesis methods for these or the compounds that serve as their raw materials are also being actively studied.
例えは、一般式［１１］
［式中、ＲＯは低級アルキル基を示し、ＲはＲＯＣＯ−
て示されるアシル基（Ｒ，Ｏは前記に同し。）を示す。For example, general formula [11] [wherein RO represents a lower alkyl group, R is ROCO-
represents an acyl group (R and O are the same as above).
Ｒ１及びＲ２は何れか一方か一０Ｒ（Ｒは前記に同じ。Either R1 or R2 is 10R (R is the same as above.
）を示し、他方は水素原子を示す。コて表わされる、オ
キサゾリン環を有するアミノ糖誘導体もこれらの原料或
は中間体として有用なものの一つである。この化合物の
合成法として従来より知られているものとしては、例え
はＪ、Ｏｒｇ、Ｃｈｅｍ、、３３．３５８５−３５８８
頁（１９６８）；Ｃａｒｂｏｈｙｄｒａｔｅ Ｒｅ５ｅ
ａｒｃｈ、２１，４６０−４６４頁＜１９７２）等に報
告されている、２−アセトアミド−１，３，４，６−テ
トラ−０−アセチル−２−デオキシ−β−Ｄ−クルコピ
ラノース（ペンタアセチルβ−ローグルコサミン）を原
料とし、縮合剤としてＦｅＣｌ３或はＺｎＣｌ２等を用
いることにより合成する方法か挙げられる。しかしなか
ら、これらの方法は、いずれも原料として合成か厄介な
β体のペンタアセチルＤ−クルコサミンを用いなけれは
ならないという制約を有していた。一方、現在のところ
、β体のペンタアセチルＤ−クルコサミンは、例えはＣ
ｈｅｍｉｓｃｈｅ Ｂｅｒｉｃｈｔｅ、６４，９７５−
９８０頁（＋９３１）等に記載されているように、Ｄ−
クルコサミンから４工程もの煩雑な操作を経なけれは合
成することができない。以下にその合成経路を簡単に示
す。) and the other represents a hydrogen atom. Amino sugar derivatives having an oxazoline ring, represented by , are also useful as raw materials or intermediates for these. Conventionally known methods for synthesizing this compound include, for example, J, Org, Chem, 33.3585-3588
Page (1968); Carbohydrate Re5e
2-acetamido-1,3,4,6-tetra-0-acetyl-2-deoxy-β-D-curcopyranose (pentaacetyl β - low glucosamine) as a raw material and using FeCl3, ZnCl2, etc. as a condensing agent. However, all of these methods have the limitation that they must use β-form pentaacetyl D-curcosamine, which is difficult to synthesize, as a raw material. On the other hand, at present, β-form pentaacetyl D-curcosamine, for example, C
Hemische Berichte, 64,975-
As described on page 980 (+931) etc., D-
It cannot be synthesized from curcosamine without undergoing four complicated steps. The synthetic route is briefly shown below.
従って、目的とする一般式［１１］で示されるアミン糖
誘導体をＤ−クルコサミンから得ようとずれは、必然的
に工程数が長くなり操作か煩雑とならざるを得なかった
。Therefore, in order to obtain the desired amine sugar derivative represented by the general formula [11] from D-curcosamine, the number of steps is inevitably increased and the operation becomes complicated.
それ故、一般式［１１１］で示されるアミノ糖誘導体を
より簡便で且つより効率よく合成し得る新規な合成法の
出現が待ち望まれていた。Therefore, the emergence of a new synthetic method that can more easily and efficiently synthesize the amino sugar derivative represented by the general formula [111] has been awaited.
［発明の目的コ
本発明は、上記した如き状況に鑑みなされたもので、オ
キサゾリン環を有するアミノ糖誘導体の簡便で且つ効率
の良い製造法を提供することを目的とする。[Object of the Invention] The present invention was made in view of the above-mentioned situation, and an object thereof is to provide a simple and efficient method for producing an amino sugar derivative having an oxazoline ring.
［発明の構成］
本発明は、一般式［１１
［式中、ＲはＲＯＣＯ−て示されるアシル基（但し、Ｒ
Ｏは低級アルキル基を示す。）を示す。Ｒ１及びＲ２は
何れか一方か一０Ｒ（Ｒは前記に同し。[Structure of the Invention] The present invention relates to the general formula [11 [wherein, R is an acyl group represented by ROCO-] (However, R
O represents a lower alkyl group. ) is shown. Either R1 or R2 is 10R (R is the same as above.
）を示し、他方は水素原子を示す。コ
て表わされるベンタアシルクルコサミン又はペンタアシ
ルカラクトサミンなトリアルキルシリルバ−フルオロア
ルカンスルポン酸又はこれらの塩と反応させることを特
徴とする、
（式中、Ｒ，ＲＯｌＲｌ及びＲ２は前記に同し。）で表
わされるアミノ糖誘導体の製造法である。) and the other represents a hydrogen atom. (wherein R, ROlRl and R2 are as defined above). This is a method for producing an amino sugar derivative represented by (same.).
一般式［１］及び一般式［１１］に於けるＲはＲＯＣＯ
−て示されるアシル基（但し、Ｒｏは例えばメチル基、
エチル基、プロピル基等の低級アルキル基を示す。）を
表わし、該アシル基としては例えはアセチル基、プロピ
オニル基、フタノイル基等が挙けられる。Ｒ１及びＲ２
の何れか一方は−ＯＲ（Ｒは前記に同し。）を表わし、
他方は水素原子を表わす。即ち、一般式［１］で示され
る化合物の基本骨格は、Ｄ−クルコサミン若しくは〇−
カラクトサミンを表わし、α体、β体の何れにてもよく
、また、官能基は全て上記した如きアシル基により保護
されている。R in general formula [1] and general formula [11] is ROCO
-Acyl group represented by (however, Ro is, for example, a methyl group,
Indicates a lower alkyl group such as an ethyl group or a propyl group. ), and examples of the acyl group include an acetyl group, a propionyl group, a phthanoyl group, etc. R1 and R2
Either one of represents -OR (R is the same as above),
The other represents a hydrogen atom. That is, the basic skeleton of the compound represented by the general formula [1] is D-curcosamine or 〇-
It represents calactosamine and may be in either the α-form or the β-form, and all functional groups are protected by the above-mentioned acyl groups.
本発明で用いられるトリアルキルシリルパーフルオロア
ルカンスルホン酸としては、例えばトリメチルシリルト
リフルオロメタンスルホン酸、トリエチルシリルトリフ
ルオロメタンスルホン酸。Examples of the trialkylsilyl perfluoroalkanesulfonic acid used in the present invention include trimethylsilyltrifluoromethanesulfonic acid and triethylsilyltrifluoromethanesulfonic acid.
トリイソプロピルシリルトリフルオロメタンスルホン酸
、トリメチルシリルペンタフルオロエタンスルホン酸、
トリメチルシリルヘプタフルオロプロパンスルホン酸、
トリエチルシリルペンタフルオロエタンスルホン酸、ジ
メチル ｔ−ブチルシリルトリフルオロメタンスルホン
酸、ジメチル ｔ−プチルシリルペンタフルオロエタン
スルホン酸。triisopropylsilyltrifluoromethanesulfonic acid, trimethylsilylpentafluoroethanesulfonic acid,
trimethylsilylheptafluoropropanesulfonic acid,
Triethylsilylpentafluoroethanesulfonic acid, dimethyl t-butylsilyltrifluoromethanesulfonic acid, dimethyl t-butylsilylpentafluoroethanesulfonic acid.
ジメチル ｔ−ブチルシリルへブタフルオロプロパンス
ルホン酸等が挙けられ、本発明で用いられるこれらの塩
としては、例えはナトリウム、カリウム、リチウム等の
アルカリ金属塩やアンモニウム塩等が挙けられる。Dimethyl t-butylsilyl hebutafluoropropanesulfonic acid and the like are mentioned, and examples of the salts thereof used in the present invention include alkali metal salts such as sodium, potassium, and lithium, and ammonium salts.
以下、本発明の製造法について記す。The manufacturing method of the present invention will be described below.
一般式［１１て示されるアシル化アミノ糖を、適当量の
ジクロロメタン、ジクロロエタン、クロロホルム、四塩
化炭素等の非極性溶媒（充分に脱水したものか望ましい
。）に溶解し、これにトリアルキルシリルパーフルオロ
アルカンスルホン酸、例えはトリメチルシリルトリフル
オロメタンスルホン酸（以下、ＴＭＳＯＴｆと略記する
。）を一般式１１．１］て示されるアシル化アミノ糖に
対して通常１〜５倍モル好ましくは１〜３培モル量加え
、通常室温乃至７０°Ｃて１〜１０時間、撹拌下に反応
させる。An acylated amino sugar represented by the general formula [11] is dissolved in an appropriate amount of a nonpolar solvent such as dichloromethane, dichloroethane, chloroform, or carbon tetrachloride (preferably a sufficiently dehydrated one), Fluoroalkanesulfonic acid, such as trimethylsilyltrifluoromethanesulfonic acid (hereinafter abbreviated as TMSOTf), is usually added in a molar amount of 1 to 5 times, preferably 1 to 3 times the amount of the acylated amino sugar represented by the general formula 11.1]. A molar amount is added, and the mixture is reacted with stirring, usually at room temperature to 70°C for 1 to 10 hours.
反応後は常法に従い生成物をジクロロメタン、ジクロロ
エタン、り００ホルム、四塩化炭素等の非極性溶媒で抽
出し、油層をアルカリ溶液及び水で順次洗浄した後Ｎ
ａ ２ Ｓ Ｏ４＋ Ｍｇ ＳＯａ等の乾燥剤で乾燥し
、溶媒を留去ずれは目的のアミノ糖誘導体のシロップが
高収率で得られる。要ずれは、更にこれを適当な精製法
、例えばカラムクロマトクラフィー等により精製すれは
、より高純度のアミノ糖誘導体が得られる。After the reaction, the product is extracted with a nonpolar solvent such as dichloromethane, dichloroethane, RI00 form, or carbon tetrachloride according to a conventional method, and the oil layer is sequentially washed with an alkaline solution and water, and then N
After drying with a desiccant such as a 2 S O4 + Mg SOa and distilling off the solvent, a syrup of the desired amino sugar derivative can be obtained in high yield. If necessary, this can be further purified by an appropriate purification method, such as column chromatography, to obtain a more highly purified amino sugar derivative.
一般式［Ｉ］で示されるアシル化アミノ糖は、Ｄ−グル
コサミン或はＤ−カラクトサミンに、アシル化剤、例え
ば無水酢酸等の酸無水物や塩化アセチル等の酸塩化物等
を反応させる常法により、１工程で容易に得ることがで
きるのでこのようにして得たものを用いることで足りる
。The acylated amino sugar represented by the general formula [I] can be produced by a conventional method in which D-glucosamine or D-calactosamine is reacted with an acylating agent, such as an acid anhydride such as acetic anhydride or an acid chloride such as acetyl chloride. Since it can be easily obtained in one step, it is sufficient to use the product obtained in this way.
以下に実施例を挙けて本発明を更に詳細に説明するが、
本発明はこれら実施例により何ら限定されるものではな
い。The present invention will be explained in more detail with reference to Examples below.
The present invention is not limited in any way by these Examples.
［実施例］
実施例１゜
２−アセトアミド−１，３，４，６−テトラ−０−アセ
チル−２−デオキシ−Ｄ−グルコビラノース １８を充
分に脱水したジクロロメタン１０ｍ１に溶解し、これに
ＴＭＳＯＴｆＯ−５５ｍｌを加え、還流下に５時間撹拌
、反応させた。反応終了後、反応液にジクロロメタンを
加えて抽出し、ジクロロメタン層を２８−Ｎａ２ＣＯ３
水溶液及び水で順次洗浄した後、Ｎａ２５Ｏ，、て乾燥
し、減圧濃縮して、シロップ状の４．５−（３，４，６
−）リー０−アセチルー２−デオキシ−０−クルコビラ
ノ）−２−メチル−Δ２−オキサゾリン０．７０ｇを得
た（収率 ８３％）。[Example] Example 1 2-acetamido-1,3,4,6-tetra-0-acetyl-2-deoxy-D-glucobylanose 18 was dissolved in 10 ml of sufficiently dehydrated dichloromethane, and TMSOTfO was added to this. -55 ml was added, and the mixture was stirred and reacted under reflux for 5 hours. After the reaction is completed, dichloromethane is added to the reaction solution for extraction, and the dichloromethane layer is extracted with 28-Na2CO3.
After sequentially washing with an aqueous solution and water, drying over Na25O, and concentrating under reduced pressure, a syrup-like 4.5-(3,4,6
-) 0-acetyl-2-deoxy-0-curcobylano)-2-methyl-Δ2-oxazoline (0.70 g) was obtained (yield: 83%).
Ｉ Ｒ（ｎｅａｔ） ： １７４０〜１７５０
（Ｃ二ｏ）、 １６７０（Ｃ＝Ｎ）ｃ＋Ｎ ’。IR(neat): 1740-1750
(C2o), 1670 (C=N)c+N'.
実施例２゜
２−アセトアミド−１，３，４，６−チトラーＯ−アセ
チルー２−デオキシ−Ｄ−カラクトビラノース０．３９
ｇを充分に脱水したジクロロメタン３ｍｌに溶解し、こ
れにＴＭＳＯＴｆ ０．２２ｍ１を加え、還流下に５時
間攪拌、反応させた。反応終了後、反応液にジクロロメ
タンを加えて抽出し、ジクロロメタン層を２Ｎ−Ｎａ２
ＣＯ３水溶液及び水で順次洗浄した後、Ｎａ２ＳＯ４て
乾燥し、減圧濃縮して、シロップ状の４．５−（３，４
，６−）リーＯ−アセチルー２−デオキシ−Ｄ−カラク
トピラノ）−２−メチル−Δ２−オキサソリン０．３２
ｇを得た（収率 ９７％）。Example 2゜2-acetamido-1,3,4,6-chitler O-acetyl-2-deoxy-D-calactobyranose 0.39
g was dissolved in 3 ml of sufficiently dehydrated dichloromethane, 0.22 ml of TMSOTf was added thereto, and the mixture was stirred and reacted under reflux for 5 hours. After the reaction is completed, dichloromethane is added to the reaction solution for extraction, and the dichloromethane layer is diluted with 2N-Na2.
After sequentially washing with CO3 aqueous solution and water, drying with Na2SO4 and concentrating under reduced pressure, syrup-like 4.5-(3,4
,6-)-O-acetyl-2-deoxy-D-calactopyrano)-2-methyl-Δ2-oxasorin 0.32
g (yield 97%).
Ｉ Ｒ（ｐｅａｔ） ： １７４０〜１７５０（Ｃ−
［１）、１６７０ＣＣ＝Ｎ＞ｃＮ’。IR (peat): 1740-1750 (C-
[1), 1670CC=N>cN'.
［発明の効果］
以上述べた如く、本発明は、医薬品、免疫薬剤等の原料
、中間体として有用なアミン糖誘導体の新規で有用な製
造法を提供するものであり、５工程もの操作を要してい
た従来法に比へて、工程数が少なく簡便であり、且つ効
率も良い等の点に顕著な効果を奏する発明であり、斯業
に貢献するところ大なる発明である。[Effects of the Invention] As described above, the present invention provides a new and useful method for producing amine sugar derivatives useful as raw materials and intermediates for pharmaceuticals, immunological agents, etc., and requires as many as five steps. This invention has remarkable effects in that it has fewer steps, is simpler, and is more efficient than the conventional method, and it is a great invention that will contribute to this industry.
手続補正書Procedural amendment
Claims (2)
Ｒ＾０は低級アルキル基を示す。）を示す。Ｒ＾１及び
Ｒ＾２は何れか一方が−ＯＲ（Ｒは前記に同じ。 ）を示し、他方は水素原子を示す。］ で表わされるペンタアシルグルコサミン又はペンタアシ
ルガラクトサミンをトリアルキルシリルパーフルオロア
ルカンスルホン酸又はこれらの塩と反応させることを特
徴とする、一般式［II］ ▲数式、化学式、表等があります▼［II］ （式中、Ｒ、Ｒ＾０、Ｒ＾１及びＲ＾２は前記に同じ。 ）で表わされるアミノ糖誘導体の製造法。(1) General formula [I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼[I] [In the formula, R is an acyl group represented by R^0CO- (However,
R^0 represents a lower alkyl group. ) is shown. One of R^1 and R^2 represents -OR (R is the same as above), and the other represents a hydrogen atom. General formula [II] characterized by reacting pentaacylglucosamine or pentaacylgalactosamine represented by [II] with trialkylsilyl perfluoroalkanesulfonic acid or a salt thereof ▲There are mathematical formulas, chemical formulas, tables, etc.▼[II ] (In the formula, R, R^0, R^1 and R^2 are the same as above.) A method for producing an amino sugar derivative represented by the following.
ン酸が、トリメチルシリルトリフルオロメタンスルホン
酸である、特許請求の範囲第１項に記載の製造法。(2) The manufacturing method according to claim 1, wherein the trialkylsilyl perfluoroalkanesulfonic acid is trimethylsilyltrifluoromethanesulfonic acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP170888A JPH01180894A (en) | 1988-01-07 | 1988-01-07 | Novel production of amino sugar derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP170888A JPH01180894A (en) | 1988-01-07 | 1988-01-07 | Novel production of amino sugar derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH01180894A true JPH01180894A (en) | 1989-07-18 |
Family
ID=11509050
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP170888A Pending JPH01180894A (en) | 1988-01-07 | 1988-01-07 | Novel production of amino sugar derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01180894A (en) |
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0464995U (en) * | 1990-10-15 | 1992-06-04 | ||
| WO2012040719A3 (en) * | 2010-09-24 | 2012-05-31 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Novel tlr4 inhibitors for the treatment of human infectious and inflammatory disorders |
| JP2013213037A (en) * | 2006-08-31 | 2013-10-17 | Simon Fraser Univ | Selective glycosidase inhibitor and use thereof |
| US9072760B2 (en) | 2010-09-24 | 2015-07-07 | University of Pittsburgh—of the Commonwealth System of Higher Education | TLR4 inhibitors for the treatment of human infectious and inflammatory disorders |
| US9120781B2 (en) | 2010-05-11 | 2015-09-01 | Simon Fraser University | Selective glycosidase inhibitors and uses thereof |
| US9199949B2 (en) | 2011-06-27 | 2015-12-01 | Alectos Therapeutics Inc. | Selective glycosidase inhibitors and uses thereof |
| US9243020B2 (en) | 2010-12-23 | 2016-01-26 | Alectos Therapeutics Inc. | Selective glycosidase inhibitors and uses thereof |
| US9409924B2 (en) | 2011-06-27 | 2016-08-09 | Alectos Therapeutics Inc. | Selective glycosidase inhibitors and uses thereof |
| US9549980B2 (en) | 2007-04-19 | 2017-01-24 | University of Pittsburgh—of the Commonwealth System of Higher Education | Methods of treating necrotizing enterocolitis by administering nuclear oligomerization domain-2 agonists,TLR9 agonists and TLR4 antagonists |
| US9562066B2 (en) | 2012-09-25 | 2017-02-07 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Oral therapy of necrotizing enterocolitis |
| US9670195B2 (en) | 2012-08-31 | 2017-06-06 | Alectos Therapeutics Inc. | Glycosidase inhibitors and uses thereof |
| US9695197B2 (en) | 2012-10-31 | 2017-07-04 | Alectos Therapeutics Inc. | Glycosidase inhibitors and uses thereof |
| US9701693B2 (en) | 2011-06-27 | 2017-07-11 | Alectos Therapeutics Inc. | Selective glycosidase inhibitors and uses thereof |
| US9718854B2 (en) | 2011-03-31 | 2017-08-01 | Alectos Therapeutics Inc. | Selective glycosidase inhibitors and uses thereof |
| US9809537B2 (en) | 2012-08-31 | 2017-11-07 | Alectos Therapeutics Inc. | Glycosidase inhibitors and uses thereof |
| US10172848B2 (en) | 2010-12-22 | 2019-01-08 | University of Pittsburgh—Of the Commonwealth Systems of Higher Education | Gap junction-enhancing agents for treatment of necrotizing enterocolitis and inflammatory bowel disease |
| US11413299B2 (en) | 2010-09-24 | 2022-08-16 | The Johns Hopkins University | Compositions and methods for treatment of inflammatory disorders |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01503382A (en) * | 1986-07-31 | 1989-11-16 | ザ・ゼネラル・ホスピタル・コーポレイション | Method for producing peracetyloxazolines |
-
1988
- 1988-01-07 JP JP170888A patent/JPH01180894A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01503382A (en) * | 1986-07-31 | 1989-11-16 | ザ・ゼネラル・ホスピタル・コーポレイション | Method for producing peracetyloxazolines |
Cited By (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0464995U (en) * | 1990-10-15 | 1992-06-04 | ||
| JP2013213037A (en) * | 2006-08-31 | 2013-10-17 | Simon Fraser Univ | Selective glycosidase inhibitor and use thereof |
| US8962664B2 (en) | 2006-08-31 | 2015-02-24 | Simon Fraser University | Selective glycosidase inhibitors and uses thereof |
| US9549980B2 (en) | 2007-04-19 | 2017-01-24 | University of Pittsburgh—of the Commonwealth System of Higher Education | Methods of treating necrotizing enterocolitis by administering nuclear oligomerization domain-2 agonists,TLR9 agonists and TLR4 antagonists |
| US9120781B2 (en) | 2010-05-11 | 2015-09-01 | Simon Fraser University | Selective glycosidase inhibitors and uses thereof |
| US9072760B2 (en) | 2010-09-24 | 2015-07-07 | University of Pittsburgh—of the Commonwealth System of Higher Education | TLR4 inhibitors for the treatment of human infectious and inflammatory disorders |
| US11413299B2 (en) | 2010-09-24 | 2022-08-16 | The Johns Hopkins University | Compositions and methods for treatment of inflammatory disorders |
| US10933077B2 (en) | 2010-09-24 | 2021-03-02 | University of Pittsburgh—of the Commonwealth System of Higher Education | TLR4 inhibitors for the treatment of human infectious and inflammatory disorders |
| US10300083B2 (en) | 2010-09-24 | 2019-05-28 | University of Pittsburgh—of the Commonwealth System of Higher Education | TLR4 inhibitors for the treatment of human infectious and inflammatory disorders |
| US9532999B2 (en) | 2010-09-24 | 2017-01-03 | University of Pittsburgh—of the Commonwealth System of Higher Education | TLR4 inhibitors for the treatment of human infectious and inflammatory disorders |
| WO2012040719A3 (en) * | 2010-09-24 | 2012-05-31 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Novel tlr4 inhibitors for the treatment of human infectious and inflammatory disorders |
| US10172848B2 (en) | 2010-12-22 | 2019-01-08 | University of Pittsburgh—Of the Commonwealth Systems of Higher Education | Gap junction-enhancing agents for treatment of necrotizing enterocolitis and inflammatory bowel disease |
| US9815861B2 (en) | 2010-12-23 | 2017-11-14 | Alectos Therapeutics, Inc. | Selective glycosidase inhibitors and uses thereof |
| US9243020B2 (en) | 2010-12-23 | 2016-01-26 | Alectos Therapeutics Inc. | Selective glycosidase inhibitors and uses thereof |
| US9718854B2 (en) | 2011-03-31 | 2017-08-01 | Alectos Therapeutics Inc. | Selective glycosidase inhibitors and uses thereof |
| US9701693B2 (en) | 2011-06-27 | 2017-07-11 | Alectos Therapeutics Inc. | Selective glycosidase inhibitors and uses thereof |
| US9409924B2 (en) | 2011-06-27 | 2016-08-09 | Alectos Therapeutics Inc. | Selective glycosidase inhibitors and uses thereof |
| US9199949B2 (en) | 2011-06-27 | 2015-12-01 | Alectos Therapeutics Inc. | Selective glycosidase inhibitors and uses thereof |
| US9809537B2 (en) | 2012-08-31 | 2017-11-07 | Alectos Therapeutics Inc. | Glycosidase inhibitors and uses thereof |
| US9670195B2 (en) | 2012-08-31 | 2017-06-06 | Alectos Therapeutics Inc. | Glycosidase inhibitors and uses thereof |
| US9562066B2 (en) | 2012-09-25 | 2017-02-07 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Oral therapy of necrotizing enterocolitis |
| US9695197B2 (en) | 2012-10-31 | 2017-07-04 | Alectos Therapeutics Inc. | Glycosidase inhibitors and uses thereof |
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