JPH03251595A - N-acetyl-beta-d-glucosaminyl-l-serine, intermediate thereof and production thereof - Google Patents
N-acetyl-beta-d-glucosaminyl-l-serine, intermediate thereof and production thereofInfo
- Publication number
- JPH03251595A JPH03251595A JP4240390A JP4240390A JPH03251595A JP H03251595 A JPH03251595 A JP H03251595A JP 4240390 A JP4240390 A JP 4240390A JP 4240390 A JP4240390 A JP 4240390A JP H03251595 A JPH03251595 A JP H03251595A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- acetyl
- group
- tables
- 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 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 49
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims abstract description 14
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims abstract description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 6
- 239000000126 substance Substances 0.000 claims description 20
- 229960001153 serine Drugs 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 2
- 108020004414 DNA Proteins 0.000 abstract description 5
- 102000053602 DNA Human genes 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- 230000006196 deacetylation Effects 0.000 abstract description 2
- 238000003381 deacetylation reaction Methods 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 abstract 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 10
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 8
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- -1 N-acetyl-β-D-glucosaminyl-monoserine Chemical compound 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 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 4
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 4
- 229950006780 n-acetylglucosamine Drugs 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 210000003855 cell nucleus Anatomy 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000000850 deacetylating effect Effects 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 2
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- 101100096444 Drosophila melanogaster spin gene Proteins 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- OAIVIYSBZFEOIU-UHFFFAOYSA-N chloroform;propan-2-one Chemical compound CC(C)=O.ClC(Cl)Cl OAIVIYSBZFEOIU-UHFFFAOYSA-N 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000006264 debenzylation reaction Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 230000001279 glycosylating effect Effects 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は、デオキシリボ核酸（ＤＮＡ）の転写調節に重
要なＮ−アセチル−β−Ｄ−グルコサミニル−し一セリ
ン及びその中間体並びにそれらの製造法に関する。Detailed Description of the Invention (Industrial Application Field) The present invention relates to N-acetyl-β-D-glucosaminyl-monoserine and its intermediates, which are important for the transcriptional regulation of deoxyribonucleic acid (DNA), and their production. Regarding the law.
（従来の技術）
Ｎ−アセチル−β−Ｄ−グルコサミニル−し一セリン及
びその中間体は、セリン又はその誘導体とＮ−アセチル
グルコサミン又はその誘導体との結合体である。(Prior Art) N-acetyl-β-D-glucosaminyl-monoserine and its intermediates are conjugates of serine or its derivatives and N-acetylglucosamine or its derivatives.
最近、細胞の核にＮ−アセチルグルコサミンがセリンや
トレオニンと結合した物質が存在しており、これがＤＮ
Ａの転写調節の上で重要な役割を果たしているという報
告がなされた。しかし、この結合又は結合物質が細胞核
に特異的に存在するものなのか、また、ＤＮＡの転写調
節の上でどのような役割を果たしているのかについては
不明である。Recently, a substance in which N-acetylglucosamine is combined with serine and threonine has been found in the nucleus of cells, and this
It has been reported that this protein plays an important role in the transcriptional regulation of A. However, it is unclear whether this binding or binding substance exists specifically in the cell nucleus and what role it plays in regulating DNA transcription.
その点を解明するためには、ある程度の純度を有し、且
つ混入している他の物質の構造等が明らかであり、しか
も、ある程度績とまった量の物質が必要である。In order to elucidate this point, it is necessary to have a substance that has a certain degree of purity, the structure of the other substances that are mixed in it, and is known in a certain amount.
（発明が解決しようとする課題）
しかしながら、Ｎ−アセチルグルコサミンがセリンやト
レオニンと結合した物質は、細胞核に存在することは知
られているが未だ単離されておらず、過去に有機合成に
より得られた記録はない。(Problem to be solved by the invention) However, although it is known that a substance in which N-acetylglucosamine is bound to serine or threonine is present in the cell nucleus, it has not yet been isolated, and in the past it was obtained by organic synthesis. There is no record of it being recorded.
以上のことから、Ｎ−アセチル−β−Ｄ−グルコサミニ
ル−し一セリン及びその中間体の有機合成方法の開発と
、それによる物質の提供が切望されていた。In view of the above, there has been a strong desire to develop an organic synthesis method for N-acetyl-β-D-glucosaminyl-monoserine and its intermediates, and to provide the substances thereby.
（課題を解決するための手段）
本発明者らは上言己課題を解決するために鋭意研究した
結果、Ｎ−アセチル−β−Ｄ−グルコサミニル−し一セ
リン及びその中間体の製造法を完成させ、それにより、
各物質を製造し、本発明を完成するに至った。(Means for Solving the Problems) As a result of intensive research to solve the above-mentioned problems, the present inventors completed a method for producing N-acetyl-β-D-glucosaminyl-monoserine and its intermediates. and thereby,
Each substance was manufactured and the present invention was completed.
このＮ−アセチル−β−Ｄ−グルコサミニル−し一セリ
ンは、新規物質であり、セリンと結合したＮ−アセチル
グルコサミンが細胞核に特異的に存在するかどうかを検
索するためのモノクロナール抗体作製用免疫原となり得
る物質である。This N-acetyl-β-D-glucosaminyl-mono-serine is a new substance, and is used as an immunization agent for producing monoclonal antibodies to detect whether N-acetylglucosamine bound to serine exists specifically in cell nuclei. It is a substance that can become a source.
また、その中間体は、上記Ｎ−アセチル−β−Ｄ−グル
コサミニル−し一セリンを製造する上で必要とされる物
質である。Moreover, the intermediate is a substance required for producing the above-mentioned N-acetyl-β-D-glucosaminyl-monoserine.
本発明の新規な化合物は、次式（１４）で表される化合
物である。The novel compound of the present invention is a compound represented by the following formula (14).
式（１４）
Ｕｔ′ｌ
（式中、Ａｃはアセチル基を示す。）
また、本発明の新規な化合物は、次式（１３）で表され
る化合物である。Formula (14) Ut'l (In the formula, Ac represents an acetyl group.) Moreover, the novel compound of the present invention is a compound represented by the following formula (13).
式（１３）
（式中、Ｂｎはベンジル基を示し、Ｚはベンジルオキシ
カルボニル基を示し、Ａｃはアセチル基を示す。）
更に、本発明は、次式
（式中、Ｂｎはベンジル基を示し、２はベンジルオキシ
カルボニル基を示す。）の化合物（１１）を、次式
（式中、Ａｃはアセチル基を示す、）
また、本発明の新規な化合物は、次式（１２）で表され
る化合物であ−る。Formula (13) (wherein, Bn represents a benzyl group, Z represents a benzyloxycarbonyl group, and Ac represents an acetyl group). , 2 represents a benzyloxycarbonyl group.) The compound (11) of the following formula (wherein, Ac represents an acetyl group) is also represented by the following formula (12): It is a compound that
式（１２）
（式中、Ａｃはアセチル基を示す、）の化合物（１０）
でグリコジル化し、次式
（式中、Ｂｎはベンジル基を示し、２はベンジルオキシ
カルボニル基を示し、Ａｃはアセチル基を示す。）で表
される化合物（１２）を製造する工程、化合物（１２）
を脱ベンジル化し、次式（式中、Ａｃはアセチル基を示
す、）で表される化合物（１４）を製造する工程、の諸
工程からなる、Ｎ−アセチル−β−Ｄ−グルコサミニル
ーＬ−セリンの製造法である。Compound (10) of formula (12) (wherein, Ac represents an acetyl group)
a step of producing a compound (12) represented by the following formula (wherein, Bn represents a benzyl group, 2 represents a benzyloxycarbonyl group, and Ac represents an acetyl group) by glycosylating with )
N-acetyl-β-D-glucosaminyl-L-serine, comprising the steps of debenzylating and producing a compound (14) represented by the following formula (wherein, Ac represents an acetyl group). This is the manufacturing method.
本発明の各物質の関係及び製造過程をスキーム１に示す
。Scheme 1 shows the relationship between the substances of the present invention and the manufacturing process.
（以下余白）
（式中、Ａｃはアセチル基を示す。）で表される化合物
（１３）を製造する工程、及び、化合物（１３）を脱ア
セチル化し、次式
スキーム
１
（式中、Ｚはベンジルオキシカルボニル基、ＢｎＣＨ。(White space below) (In the formula, Ac represents an acetyl group.) A step of producing a compound (13) represented by the following formula, and a step of deacetylating the compound (13) to obtain Benzyloxycarbonyl group, BnCH.
（１０） （１１） 以下に、本発明の内容を更に詳細に説明する。(10) (11) Below, the content of the present invention will be explained in more detail.
前記式（１２）で表される化合物〈１２）は、スキーム
１に示すように、公知の化合物である化合物（１１）［
Ｅ、 Ｂａｅｒら、リサーチｌし・オン・ザ・アメリカ
ン・ケミカル・ソサイエテ４− （Ｊｏｕｒｎａｌ ｏ
ｆ ｔｈｅＡｍｅｒｉｃａｎ Ｃｈｅｍｉｃａｌ ５ｏ
ｃｉｅｔｙ） 、８１ （１９５９） ２１６６の方法
により製造できるコを、公知の化合物である化合物（１
０） ＣＫ、 Ｌ、 Ｍａｔｔａら、カーボハイドレー
ト・リサーチ（Ｃａｒｂｏｈｙｄｒａｔｅ Ｒｅ５ｅａ
ｒｃｈ）、 ２１（１９７２） ４６０の方法により製
造できる］でグリコジル化することによって製造する。As shown in Scheme 1, the compound (12) represented by the formula (12) is a compound (11) [
E. Baer et al., Research on the American Chemical Society 4- (Journal o
f the American Chemical 5o
Society), 81 (1959) 2166, a known compound, compound (1).
0) CK, L, Matta et al., Carbohydrate Re5ea
21 (1972) 460].
このグリコジル化は、例えばジクロロエタン等の溶媒中
、ｐ−）ルエンスルホン酸く以下、ｐＴｓＯＨという〉
の存在下で実施することができる。また、グリコジル化
反応は、５〜１００℃の温度で、１分〜２４時間、反応
系を攪拌しながら行うことが好ましい。This glycosylation is carried out using p-)toluenesulfonic acid (hereinafter referred to as pTsOH) in a solvent such as dichloroethane.
can be carried out in the presence of Moreover, the glycosylation reaction is preferably carried out at a temperature of 5 to 100° C. for 1 minute to 24 hours while stirring the reaction system.
更に、化合物（１３）は、化合物（１２）を脱ベンジル
化することによって合成する。上記化合物（１２）の脱
ベンジル化は、パラジウム・ブラックの存在の下に、水
素ガス雰囲気中、メタノールやテトラヒドロフラン（以
下、ＴＨＦという）等の溶媒中、５〜１００℃の温度で
、１分〜２４時間、反応系を攪拌しながら行うことが好
ましい。Furthermore, compound (13) is synthesized by debenzylating compound (12). The debenzylation of the above compound (12) is carried out for 1 minute to 1 minute at a temperature of 5 to 100°C in a solvent such as methanol or tetrahydrofuran (hereinafter referred to as THF) in a hydrogen gas atmosphere in the presence of palladium black. It is preferable to carry out the reaction while stirring the reaction system for 24 hours.
また、化合物（１４）は化合物（１３）を脱アセチル化
することによって合成する。上記化合物（１３）の脱ア
セチル化は、メタノール等の溶媒中、ＮａＯＨ等のアル
カリで処理することによって実施することができる。Moreover, compound (14) is synthesized by deacetylating compound (13). Deacetylation of the compound (13) can be carried out by treatment with an alkali such as NaOH in a solvent such as methanol.
尚、前記工程において合成される化合物（１２）、（１
３）、（１４）は、いずれも新規化合物である。In addition, compounds (12) and (1) synthesized in the above step
3) and (14) are both new compounds.
（実施例）
以下に、実施例を挙げて本発明を更に具体的に説明する
が、本発明の範囲はこれらの例により限定されるもので
はない。(Examples) The present invention will be described in more detail below with reference to Examples, but the scope of the present invention is not limited by these Examples.
実施例１ ［化合物（１０）＋（１１）→（１２）コ化
合物（１１）１．１５ｇ （３，５ｍモル）を１゜２−
ジクロロエタン１０−に溶解し、１，２−ジクロロエタ
ン１５−に溶解した化合物（１０）１．０５ｇ （３，
２ｍモル）とｐ −Ｔ ｓ ＯＨ２０ｍ ｇを加えて、
浴温９０℃で１５時間還流した。Example 1 [Compound (10) + (11) → (12) 1.15 g (3.5 mmol) of compound (11) was mixed at 1°2-
1.05 g of compound (10) dissolved in dichloroethane 10- and 1,2-dichloroethane 15- (3,
2 mmol) and 20 mg of p-Ts OH,
The mixture was refluxed for 15 hours at a bath temperature of 90°C.
放冷後、クロロホルム２００−を加えて希釈し、重曹処
理をして、無水硫酸マグネシウムで乾燥した。濾過後、
減圧乾燥して、残渣を１８０ｇのシリカゲルカラム（溶
媒；クロロホルム−アセトン＝４：１）に通して得られ
た粗生成物をり四ロホルムー石油エーテルで結晶化し、
７０６．４ｍｇの化合物（１２〉を得な（収率３３．６
％）。After cooling, the mixture was diluted with 200% chloroform, treated with sodium bicarbonate, and dried over anhydrous magnesium sulfate. After filtration,
After drying under reduced pressure, the residue was passed through a 180 g silica gel column (solvent: chloroform-acetone = 4:1), and the resulting crude product was crystallized from tetraroform-petroleum ether.
706.4 mg of compound (12) was obtained (yield 33.6
%).
［化合物（１２）の性質］
■薄層クロマトグラフィー
Ｒｆ＝０． ３７ （りＶ！υホルム：アセトン＝４
：１ ）■元素分析（Ｃ３２Ｈ３８Ｎ２０１３として
）計算値 Ｃ＝５８．３５．８＝５．８２． Ｎ＝４．
２５測定値 Ｃ＝５８．４８． Ｈ＝５．７６、 Ｎ＝
４．３５■比旋光度
［α］２５＝−９，２°（Ｃ・０．３９． ＣＨＣｌ３
）■融点
ｍｐ＝１５６〜１５９℃
■核磁気共鳴分析（ＩＨ−Ｎ Ｍ Ｒ、ＣＤＣｌ３ ）
７．３５４（ｓ、ＩＯＨ，２Ｐｈ）
４．６８２（ｄ、ＩＨ，Ｊ８．３０Ｈｚ、Ｈ−１）■核
磁気共鳴分析（”ＣＮ Ｍ Ｒ、ＣＤＣｈ ）１００．
４７（’ＪＣ）１１６０．４Ｈ２，Ｃ−１）６８．７６
（Ｓｅｒ、β）、６１．９４（Ｃ−６）５４．４１，５
４．２６（Ｃ−２，Ｓｅｒ、ａ ）実施例２［化合物〈
１２）→（１３）］１００．６ｍｇの化合物（１２）を
メタノール５−及びＴＨＦ２ｄの混液に溶解し、ＴＨＦ
３ｄに懸濁させたパラジウムブラック２０ｍｇを加えて
、水素を封入し、室温で１６時間攪拌した。[Properties of compound (12)] ■Thin layer chromatography Rf=0. 37 (riV!υ form: acetone = 4
:1) ■Elemental analysis (as C32H38N2013) Calculated value C=58.35.8=5.82. N=4.
25 Measured value C=58.48. H=5.76, N=
4.35 ■ Specific optical rotation [α] 25 = -9.2° (C・0.39. CHCl3
) ■Melting point mp=156-159℃ ■Nuclear magnetic resonance analysis (IH-NMR, CDCl3)
7.354 (s, IOH, 2Ph) 4.682 (d, IH, J8.30Hz, H-1) ■Nuclear magnetic resonance analysis (CNMR, CDCh) 100.
47('JC)1160.4H2,C-1)68.76
(Ser, β), 61.94 (C-6) 54.41,5
4.26 (C-2, Ser, a) Example 2 [Compound
12)→(13)] 100.6 mg of compound (12) was dissolved in a mixture of methanol 5- and THF2d, and THF
20 mg of palladium black suspended in 3d was added, hydrogen was enclosed, and the mixture was stirred at room temperature for 16 hours.
次いで、セライト濾過後、減圧濃縮し、化合物（１３）
を定量的に得た。Then, after filtration through Celite, concentration under reduced pressure was performed to obtain compound (13).
was obtained quantitatively.
［化合物（１３）の性質］
■薄層クロマトグラフィー
Ｒｆ＝０． ４９ （ｎ−ツタノール−エタノール−
水＝２：１：１）■核磁気共鳴分析（’Ｈ−ＮＭＲ，Ｃ
Ｄ、ＯＤ ）４．６８４（ｄ、ＩＨ，Ｊ８．５５Ｈｚ、
）！−１）２．０５６．２．０１２，１．９ｇ４．１．
９４０（４ｓ、１２ｔｌ、４Ａｃ）■核磁気共鳴分析（
１３Ｃ−ＮＭＲ，ＣＤ、ＯＤ ）１０２．１６（’ＪＣ
）１１６２．４Ｈ２，Ｃ−１）、７４．３０（Ｃ−５＞
７３．３６（Ｃ−３）、７０．１３（Ｃ−４）。[Properties of compound (13)] ■Thin layer chromatography Rf=0. 49 (n-tutanol-ethanol-
water = 2:1:1) ■ Nuclear magnetic resonance analysis ('H-NMR, C
D, OD) 4.684 (d, IH, J8.55Hz,
)! -1) 2.056.2.012, 1.9g4.1.
940 (4s, 12tl, 4Ac) ■Nuclear magnetic resonance analysis (
13C-NMR, CD, OD) 102.16 ('JC
) 1162.4H2, C-1), 74.30 (C-5>
73.36 (C-3), 70.13 (C-4).
６９．８６（Ｓｅｒ、β）、６３．２８（Ｃ−６）５６
．４７（Ｃ−２＞、５５．２６（Ｓｅｒ、α）実施例３
［化合ＩＩ（１３）→（１４）］化合物（１３）２０１
．１ｍｇをメタノール２〇−に溶解し、ｌＮ−ＮａＯＨ
水溶液２−を加えて、室温で３時間撹拌した。69.86 (Ser, β), 63.28 (C-6) 56
．． 47 (C-2>, 55.26 (Ser, α) Example 3
[Compound II (13) → (14)] Compound (13) 201
．． Dissolve 1 mg in 20-methanol and dilute with 1N-NaOH.
Aqueous solution 2- was added and stirred at room temperature for 3 hours.
次に、冷水２０−を加えて、アンバーリスト１５［Ａｍ
ｂｅｒｌｙｓｔ１５．オルガノ■製コ２−で中和し、セ
ライトを用いて濾過した後減圧濃縮した。Next, add 20 - of cold water and add Amberlyst 15 [Am
berryst15. The mixture was neutralized with CO2 manufactured by Organo ■, filtered through Celite, and then concentrated under reduced pressure.
残渣をゲル濾過（５ｅｐｈａｄｅｘＧ−１０，１００−
１水）により精製し、凍結乾燥した後５Ｂ、４ｍｇの化
合物（１４）を得た（収率３７．４％）。The residue was subjected to gel filtration (5ephadexG-10,100-
1 water) and lyophilized to obtain 5B, 4 mg of compound (14) (yield 37.4%).
［化合物（１４）の性質］
■薄層クロマトグラフィー
Ｒｆ＝０． ２３ （ｎ−フタノール−エタノール−
水−２＋１：１）■元素分析（Ｃ１ＩＨ２ＯＮ２０ｇ
・４／３Ｈ２０として）
計算値 Ｃ＝３９．７６、８＝６．８８． Ｎ＝８．４
３測定値 Ｃ＝３９．７２．８＝６．４８． Ｎ＝８．
０７■比旋光度
［α］２５ ＝−３３，１°（Ｃ＝０．３９． Ｈ２
Ｏ）■核磁気共鳴分析（”Ｈ−ＮＭＲ，Ｄ２０ ）４．
５４８（ｄ、ＩＨ，Ｊ８．３０Ｈｚ、Ｈ−１）２．０５
０（ｓ、３Ｈ，ＮＡｃ）
■核磁気共鳴分析（”Ｃ−ＮＭＲ，Ｄ２０ ）１７５
、８０ （ＮＨＣＯＣＨ３）
１７２．４７（Ｃｏ□Ｈ）
１０１．６６（’Ｊｃｏ１６２．４Ｈｚ、Ｃ−１）７６
．６８（Ｃ−５）、７４．５ＨＣ−３）、７０．５６（
Ｃ−４）。[Properties of compound (14)] ■Thin layer chromatography Rf=0. 23 (n-phthanol-ethanol-
water-2+1:1) ■Elemental analysis (C1IH2ON20g
・As of 4/3H20) Calculated value C=39.76, 8=6.88. N=8.4
3 Measured value C=39.72.8=6.48. N=8.
07 ■ Specific optical rotation [α] 25 = -33,1° (C = 0.39. H2
O)■Nuclear magnetic resonance analysis ("H-NMR, D20)4.
548 (d, IH, J8.30Hz, H-1) 2.05
0 (s, 3H, NAc) ■Nuclear magnetic resonance analysis ("C-NMR, D20) 175
, 80 (NHCOCH3) 172.47 (Co□H) 101.66 ('Jco162.4Hz, C-1) 76
．． 68 (C-5), 74.5HC-3), 70.56 (
C-4).
６８．７５（Ｓｅｒ、β）、６１．４０（Ｃ−６＞５６
．１５（Ｃ−２＞、５５．５４（Ｓｅｒ、 ａ ） 、
２２．９９（ＮＨＣＯＣＨ３）（発明の効果）
本発明により、有機合成によってＮ−アセチル−β−Ｄ
−グルコサミニルーＬ−セリン及びその中間体を得るこ
とが可能になった。68.75 (Ser, β), 61.40 (C-6>56
．． 15(C-2>, 55.54(Ser, a),
22.99 (NHCOCH3) (Effect of the invention) According to the present invention, N-acetyl-β-D
- It has become possible to obtain glucosaminyl-L-serine and its intermediates.
Claims (1)
カルボニル基を示し、Ａｃはアセチル基を示す。） ４ 次式 ▲数式、化学式、表等があります▼ （式中、Ｂｎはベンジル基を示し、Ｚはベンジルオキシ
カルボニル基を示す。）の化合物（１１）を、次式 ▲数式、化学式、表等があります▼ （式中、Ａｃはアセチル基を示す。）の化合物（１０）
でグリコシル化し、次式 ▲数式、化学式、表等があります▼ （式中、Ｂｎはベンジル基を示し、Ｚはベンジルオキシ
カルボニル基を示し、Ａｃはアセチル基を示す。）で表
される化合物（１２）を製造する工程、化合物（１２）
を脱ベンジル化し、次式▲数式、化学式、表等がありま
す▼ （式中、Ａｃはアセチル基を示す。）で表される化合物
（１３）を製造する工程、及び、化合物（１３）を脱ア
セチル化し、次式 ▲数式、化学式、表等があります▼ （式中、Ａｃはアセチル基を示す。）で表される化合物
（１４）を製造する工程、の諸工程からなる、Ｎ−アセ
チル−β−Ｄ−グルコサミニル−Ｌ−セリンの製造法。[Claims] A compound represented by the primary formula (14). Formula (14) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, Ac represents an acetyl group.) A compound represented by the secondary formula (13). Formula (13) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, Ac represents an acetyl group.) A compound represented by the tertiary formula (12). Formula (12) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, Bn represents a benzyl group, Z represents a benzyloxycarbonyl group, and Ac represents an acetyl group.) Quaternary formula ▲ Numerical formula, chemical formula, There are tables, etc. ▼ (In the formula, Bn represents a benzyl group and Z represents a benzyloxycarbonyl group.) The compound (11) is expressed by the following formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, Ac represents an acetyl group.) Compound (10)
The compound is glycosylated with the following formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, Bn represents a benzyl group, Z represents a benzyloxycarbonyl group, and Ac represents an acetyl group.) 12) Process for producing compound (12)
A step of debenzylating and producing a compound (13) represented by the following formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, Ac represents an acetyl group.) N-acetyl- Method for producing β-D-glucosaminyl-L-serine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4240390A JPH03251595A (en) | 1990-02-26 | 1990-02-26 | N-acetyl-beta-d-glucosaminyl-l-serine, intermediate thereof and production thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4240390A JPH03251595A (en) | 1990-02-26 | 1990-02-26 | N-acetyl-beta-d-glucosaminyl-l-serine, intermediate thereof and production thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH03251595A true JPH03251595A (en) | 1991-11-11 |
Family
ID=12635103
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4240390A Pending JPH03251595A (en) | 1990-02-26 | 1990-02-26 | N-acetyl-beta-d-glucosaminyl-l-serine, intermediate thereof and production thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH03251595A (en) |
-
1990
- 1990-02-26 JP JP4240390A patent/JPH03251595A/en active Pending
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