JPH024234B2 - - Google Patents
Info
- Publication number
- JPH024234B2 JPH024234B2 JP57040171A JP4017182A JPH024234B2 JP H024234 B2 JPH024234 B2 JP H024234B2 JP 57040171 A JP57040171 A JP 57040171A JP 4017182 A JP4017182 A JP 4017182A JP H024234 B2 JPH024234 B2 JP H024234B2
- Authority
- JP
- Japan
- Prior art keywords
- glucofuranose
- isopropylidene
- benzyl
- equivalents
- reaction
- 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
Links
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 claims description 20
- 229940073608 benzyl chloride Drugs 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 13
- BGGCXQKYCBBHAH-OZRXBMAMSA-N (1r)-1-[(3ar,5r,6s,6ar)-6-hydroxy-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]ethane-1,2-diol Chemical compound O1[C@H]([C@H](O)CO)[C@H](O)[C@H]2OC(C)(C)O[C@H]21 BGGCXQKYCBBHAH-OZRXBMAMSA-N 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 6
- AVVWPBAENSWJCB-IVMDWMLBSA-N D-glucofuranose Chemical compound OC[C@@H](O)[C@H]1OC(O)[C@H](O)[C@H]1O AVVWPBAENSWJCB-IVMDWMLBSA-N 0.000 claims description 4
- 239000002798 polar solvent Substances 0.000 claims description 3
- 238000005574 benzylation reaction Methods 0.000 claims 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 238000003756 stirring Methods 0.000 description 14
- 238000000034 method Methods 0.000 description 11
- 239000000203 mixture Substances 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- RNPMTPOOMRPILB-XYPQWYOHSA-N (3ar,5r,6s,6ar)-5-[(1r)-1,2-bis(phenylmethoxy)ethyl]-2,2-dimethyl-6-phenylmethoxy-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxole Chemical compound C([C@H]([C@H]1O[C@@H]2OC(O[C@@H]2[C@H]1OCC=1C=CC=CC=1)(C)C)OCC=1C=CC=CC=1)OCC1=CC=CC=C1 RNPMTPOOMRPILB-XYPQWYOHSA-N 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- AVVWPBAENSWJCB-UKFBFLRUSA-N alpha-D-glucofuranose Chemical compound OC[C@@H](O)[C@H]1O[C@H](O)[C@H](O)[C@H]1O AVVWPBAENSWJCB-UKFBFLRUSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- -1 dibenzyl compound Chemical class 0.000 description 2
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ULLNJSBQMBKOJH-VIVFLBMVSA-N (3R,4R,5R)-5-[(1R)-1,2-bis(phenylmethoxy)ethyl]-2-ethoxy-4-phenylmethoxy-3-oxolanol Chemical compound C([C@H]([C@H]1OC([C@@H]([C@H]1OCC=1C=CC=CC=1)O)OCC)OCC=1C=CC=CC=1)OCC1=CC=CC=C1 ULLNJSBQMBKOJH-VIVFLBMVSA-N 0.000 description 1
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 1
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 1
- SUAKHGWARZSWIH-UHFFFAOYSA-N N,N‐diethylformamide Chemical compound CCN(CC)C=O SUAKHGWARZSWIH-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- AJFDBNQQDYLMJN-UHFFFAOYSA-N n,n-diethylacetamide Chemical compound CCN(CC)C(C)=O AJFDBNQQDYLMJN-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
Description
【発明の詳細な説明】
本発明は、次（）で表わされるグルコフラノ
ース誘導体の製法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a glucofuranose derivative represented by the following ().
この化合物は循環障害改善作用をはじめとして
種々の薬理作用を有するエチル３，５，６−トリ
−Ｏ−ベンジル−Ｄ−グルコフラノシドのための
製造中間体として重要である。従来、この化合物
を製造するためには次の二つの方法が知られてい
た。 This compound is important as an intermediate for the production of ethyl 3,5,6-tri-O-benzyl-D-glucofuranoside, which has various pharmacological effects including the effect of improving circulation disorders. Conventionally, the following two methods have been known for producing this compound.
(1) 原料である１，２−Ｏ−イソプロピリデン−
α−Ｄ−グルコフラノースに対して溶媒をかね
て大過剰の塩化ベンジル（3.3当量）を用い且
つ塩基として水酸化カリウム（3.5当量）を用
いる方法（特公昭36−23319号公報参照）。(1) Raw material 1,2-O-isopropylidene-
A method in which a large excess of benzyl chloride (3.3 equivalents) is used as a solvent with respect to α-D-glucofuranose, and potassium hydroxide (3.5 equivalents) is used as a base (see Japanese Patent Publication No. 36-23319).
(2) 過剰の塩化ベンジル（1.7当量）および水酸
化カリウム（1.7当量）を用い且つ溶媒として
ジオキサンを使用する方法〔「Helv.Chim.
acta」第51巻第1185頁（1968）参照〕。(2) A method using excess benzyl chloride (1.7 equivalents) and potassium hydroxide (1.7 equivalents) and dioxane as a solvent [“Helv.Chim.
Acta, Vol. 51, p. 1185 (1968)].
しかしながら、これらの両方法とも多くの欠点
を有している。すなわち、過剰の試薬を使用しな
ければならないうえに反応が完結せず、多量のジ
ベンジル化合物（３，６−ジ−Ｏ−ベンジル−
１，２−Ｏ−イソプロピリデン−α−Ｄ−グルコ
フラノースおよび５，６−Ｏ−ベンジル−１，２
−Ｏ−イソプロピリデン−α−Ｄ−グルコフラノ
ース）が副生し、これを除去精製するのは非常に
困難である。反応操作の上でも、反応途中で粉末
水酸化カリウムが粘着性を帯びて固まつてしま
い、撹拌が充分に行なえなくなつてしまう。さら
に、過剰に使用した塩化ベンジルが反応生成物
（）の中に未反応ままで残存し、蒸留精製に際
して機器に好ましくない影響を与える。 However, both of these methods have a number of drawbacks. That is, an excess of reagents must be used, the reaction is not completed, and a large amount of dibenzyl compound (3,6-di-O-benzyl-
1,2-O-isopropylidene-α-D-glucofuranose and 5,6-O-benzyl-1,2
-O-isopropylidene-α-D-glucofuranose) is produced as a by-product, and it is very difficult to remove and purify it. In terms of reaction operation, the powdered potassium hydroxide becomes sticky and hardens during the reaction, making it impossible to stir the mixture sufficiently. Furthermore, the benzyl chloride used in excess remains unreacted in the reaction product (2), which has an undesirable effect on equipment during distillation and purification.
本発明者等はこれらの欠点を改良すべく研究を
重ねた結果、本発明を完成するに至つた。従つて
本発明の目的は上記（）式で表わされる化合物
を工業的に有利に製造する方法を提供するにあ
る。以下に本発明を詳細に説明する。 As a result of repeated research to improve these drawbacks, the present inventors have completed the present invention. Therefore, an object of the present invention is to provide an industrially advantageous method for producing the compound represented by the above formula (). The present invention will be explained in detail below.
本発明によれば、１，２−Ｏ−イソプロピリデ
ン−α−Ｄ−グルコフラノースを非プロトン性極
性溶媒中で塩基の存在下に塩化ベンジルと反応せ
しめて上記（）式で表わされる３，５，６−ト
リ−Ｏ−ベンジル−１，２−Ｏ−イソプロピリデ
ン−α−Ｄ−グルコフラノースを得る。この反応
に用いる塩基としては水酸化ナトリウム、水酸化
カリウム、水素化ナトリウム等が挙げられる。溶
媒としては一般に知られている非プロトン性極性
溶媒例えばジメチルスルホキシド、ジメチルホル
ムアミド、ジメチルホルムアミド、ジメチルアセ
トアミド、ジエチルアセトアミド、ジエチルホル
ムアミド、Ｎ−メチル−２−ピロリドン、１，３
−ジメチル−２−イミダゾリドン、テトラメチル
尿素、リン酸ヘキサメチルトリアミド等が挙げら
れる。溶媒の使用量は場合によつて異なるが、一
般に原料である１，２−Ｏ−イソプロピリデン−
α−Ｄ−グルコフラノースに対して５倍（ｖ／
ｗ）以上が適当である。反応温度は0゜から70°の
範囲が使用できるが一般には室温で好結果を与え
る。 According to the present invention, 1,2-O-isopropylidene-α-D-glucofuranose is reacted with benzyl chloride in an aprotic polar solvent in the presence of a base to obtain 3,5 , 6-tri-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose. Examples of the base used in this reaction include sodium hydroxide, potassium hydroxide, and sodium hydride. As the solvent, commonly known aprotic polar solvents such as dimethyl sulfoxide, dimethylformamide, dimethylformamide, dimethylacetamide, diethylacetamide, diethylformamide, N-methyl-2-pyrrolidone, 1,3
-dimethyl-2-imidazolidone, tetramethylurea, hexamethyltriamide phosphate, and the like. The amount of solvent used varies depending on the case, but generally the raw material 1,2-O-isopropylidene-
5 times (v/
w) The above is appropriate. The reaction temperature can range from 0° to 70°, but good results are generally obtained at room temperature.
本発明の方法によれば、1.2当量の塩化ベンジ
ルを用いれば反応はほぼ完全に進行し、先行技術
におけるようなジベンジル化合物はほとんど副生
しない。反応途中の撹拌も容易である。さらに塩
化ベンジルの過剰分は最終的に完全にジベンジル
エーテルに変換されるために蒸留精製に際し機器
に悪影響を与えることもない。 According to the method of the present invention, when 1.2 equivalents of benzyl chloride is used, the reaction proceeds almost completely, and hardly any dibenzyl compound is produced as a by-product as in the prior art. Stirring during the reaction is also easy. Furthermore, since the excess benzyl chloride is finally completely converted into dibenzyl ether, it does not adversely affect the equipment during distillation and purification.
本発明方法で得られた化合物（）は不純物が
極めて少ないため特に精製することなく次段の反
応例えばエチル３，５，６−トリ−Ｏ−ベンジル
−Ｄ−グリコフラノシドの製造に支障なく使用で
きる。以上のように本発明は工業的に極めて有利
な化合物（）の製造法である。 Since the compound () obtained by the method of the present invention has very few impurities, it can be used without any particular purification in the next reaction, such as the production of ethyl 3,5,6-tri-O-benzyl-D-glycofuranoside. can. As described above, the present invention is an industrially extremely advantageous method for producing compound ().
次に本発明の実施例を示すが、本発明はこれら
の例によつて制限をうけるものではない。 Next, examples of the present invention will be shown, but the present invention is not limited to these examples.
実施例 １
１，２−Ｏ−イソプロピリデン−α−Ｄ−グル
コフラノース300ｇをジメチルスルホキシド1.7
〔5.7倍（ｖ／ｗ）〕に溶解し、次いで粉末水酸化
ナトリウム144ｇ（0.84当量）を加える。30℃で
１時間撹拌した後、塩化ベンジル430ｇ（0.83当
量）を約１時間かけて滴下し、さらに１時間撹拌
する。粉末水酸化ナトリウム114ｇ（0.66当量）
を加え、10℃以下に冷却し、そして塩化ベンジル
187ｇ（0.36当量）を滴下する。10℃以下で１時
間撹拌した後、ゆつくり温度を上げ、20℃で15時
間そして70℃で２時間反応せしめる。反応物をト
ルエンで抽出し、抽出液を水および飽和食塩水で
順次洗つた後無水硫酸ナトリウムで乾燥する。溶
媒を減圧留去すれば３，５，６−トリ−Ｏ−ベン
ジル−１，２−Ｏ−イソプロピリデン−α−Ｄ−
グルコフラノース760ｇを得る。純度87.7％（収
率99.6％）。Example 1 300 g of 1,2-O-isopropylidene-α-D-glucofuranose was mixed with 1.7 g of dimethyl sulfoxide.
[5.7 times (v/w)] and then add 144 g (0.84 equivalents) of powdered sodium hydroxide. After stirring at 30° C. for 1 hour, 430 g (0.83 equivalents) of benzyl chloride was added dropwise over about 1 hour, followed by further stirring for 1 hour. Powdered sodium hydroxide 114g (0.66 equivalent)
was added, cooled to below 10°C, and benzyl chloride
Add 187 g (0.36 equivalents) dropwise. After stirring at below 10°C for 1 hour, the temperature was slowly raised and the reaction was carried out at 20°C for 15 hours and at 70°C for 2 hours. The reaction product was extracted with toluene, and the extract was washed successively with water and saturated brine, and then dried over anhydrous sodium sulfate. When the solvent is distilled off under reduced pressure, 3,5,6-tri-O-benzyl-1,2-O-isopropylidene-α-D-
Obtain 760g of glucofuranose. Purity 87.7% (yield 99.6%).
なお粗生成物中に含まれる５，６−ジ−Ｏ−ベ
ンジル−１，２−Ｏ−イソプロピリデン−α−Ｄ
−グルコフラノースは０％であり、また３，６−
ジ−Ｏ−ベンジル−１，２−Ｏ−イソプロピリデ
ン−α−Ｄ−グルコフラノースは0.12％である。 Furthermore, 5,6-di-O-benzyl-1,2-O-isopropylidene-α-D contained in the crude product
- Glucofuranose is 0% and 3,6-
Di-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose is 0.12%.
実施例 ２
１，２−Ｏ−イソプロピリデン−α−Ｄ−グル
コフラノース22ｇをジメチルアセトアミド132ml
〔６倍（ｖ／ｗ）〕に溶解し、これに粉末水酸化カ
リウム16.8ｇ（0.85当量）を加え、次いで30℃で
１時間撹拌する。塩化ベンジル31ｇ（0.82当量）
を滴下し、１時間撹拌した後、粉末水酸化カリウ
ム13ｇ（0.66当量）を加える。10℃以下に冷却
し、塩化ベンジル14.4ｇ（0.38当量）を滴下し、
そのまま１時間撹拌する。ゆつくり温度を上昇さ
せて20℃で15時間、次いで70℃で２時間反応せし
める。反応混合物をトルエンで抽出し、以後実施
例１と同様に操作して粗製の３，５，６−トリ−
Ｏ−ベンジル−１，２−Ｏ−イソプロピリデン−
α−Ｄ−グルコフラノース56.5ｇを得る。純度
84.9％（収率97.9％）。Example 2 22 g of 1,2-O-isopropylidene-α-D-glucofuranose was added to 132 ml of dimethylacetamide.
[6 times (v/w)], add 16.8 g (0.85 equivalents) of powdered potassium hydroxide, and then stir at 30°C for 1 hour. Benzyl chloride 31g (0.82 equivalent)
was added dropwise, and after stirring for 1 hour, 13 g (0.66 equivalents) of powdered potassium hydroxide was added. Cool to below 10°C, add 14.4g (0.38 equivalents) of benzyl chloride dropwise,
Stir as is for 1 hour. The temperature was increased slowly and the reaction was carried out at 20°C for 15 hours and then at 70°C for 2 hours. The reaction mixture was extracted with toluene, and then the same procedure as in Example 1 was performed to obtain the crude 3,5,6-tri-
O-benzyl-1,2-O-isopropylidene-
56.5 g of α-D-glucofuranose is obtained. purity
84.9% (yield 97.9%).
なお粗生成物中に含まれる５，６−ジ−Ｏ−ベ
ンジル−１，２−Ｏ−イソプロピリデン−α−Ｄ
−グルコフラノースは0.10％であり、また３，６
−ジ−Ｏ−ベンジル−１，２−Ｏ−イソプロピリ
デン−α−Ｄ−グルコフラノースは0.15％であ
る。 Furthermore, 5,6-di-O-benzyl-1,2-O-isopropylidene-α-D contained in the crude product
- Glucofuranose is 0.10% and also 3,6
-di-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose is 0.15%.
実施例 ３
水素化ナトリウム（60％）3.6％（1.5当量）を
ｎ−ヘキサンで洗滌した後、リン酸ヘキサメチル
トリアミド22ml〔５倍（ｖ／ｗ）〕中に懸濁させ
る。氷冷撹拌下に１，２−Ｏ−イソプロピリデン
−α−Ｄ−グルコフラノース4.4ｇを加え、室温
で１時間反応せしめる。塩化ベンジル6.0ｇ（0.8
当量）を滴下し、室温で１時間反応させた後、10
℃以下に冷却し、塩化ベンジル3.0ｇ（0.4当量）
を滴下する。10℃以下で１時間撹拌反応を行つた
後、ゆつくり温度を上げて20℃で15時間、そして
70℃で２時間反応せしめる。冷却後、メタノール
２mlを加え、再び70℃で２時間反応せしめる。反
応混合物をトルエンで抽出し、以後実施例１と同
様に操作して粗製の３，５，６−トリ−Ｏ−ベン
ジル−１，２−Ｏ−イソプロピリデン−α−Ｄ−
グルコフラノース10.2ｇを得る。純度87.5％（収
率91.1％）。Example 3 Sodium hydride (60%) 3.6% (1.5 equivalents) is washed with n-hexane and then suspended in 22 ml (5x (v/w)) of hexamethyltriamide phosphate. 4.4 g of 1,2-O-isopropylidene-α-D-glucofuranose was added to the mixture under ice-cooling and stirring, and the mixture was allowed to react at room temperature for 1 hour. Benzyl chloride 6.0g (0.8
equivalent amount) was added dropwise and reacted at room temperature for 1 hour, then 10
Cool to below ℃ and add 3.0 g (0.4 equivalents) of benzyl chloride.
drip. After stirring the reaction at 10°C or lower for 1 hour, the temperature was slowly raised to 20°C for 15 hours, and then
React at 70°C for 2 hours. After cooling, 2 ml of methanol was added and the mixture was reacted again at 70°C for 2 hours. The reaction mixture was extracted with toluene, and the procedure was repeated in the same manner as in Example 1 to obtain crude 3,5,6-tri-O-benzyl-1,2-O-isopropylidene-α-D-
Obtain 10.2 g of glucofuranose. Purity 87.5% (yield 91.1%).
なお粗生成物中に含まれる５，６−ジ−Ｏ−ベ
ンジル−１，２−Ｏ−イソプロピリデン−α−Ｄ
−グルコフラノースは０％であり、また３，６−
ジ−Ｏ−ベンジル−１，２−Ｏ−イソプロピリデ
ン−α−Ｄ−グルコフラノースは0.18％である。 Furthermore, 5,6-di-O-benzyl-1,2-O-isopropylidene-α-D contained in the crude product
- Glucofuranose is 0% and 3,6-
Di-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose is 0.18%.
実施例 ４
１，２−Ｏ−イソプロピリデン−α−Ｄ−グル
コフラノース22ｇをＮ−メチル−２−ピロリドン
132ml〔６倍（ｖ／ｗ）〕に溶解し、粉末水酸化ナ
トリウム10.6ｇ（0.84当量）を加え、そして１時
間撹拌する。塩化ベンジル31ｇ（0.82当量）を滴
下し且つ１時間撹拌した後、粉末水酸化ナトリウ
ム8.3ｇ（0.66当量）を加える。10℃以下に冷却
し、塩化ベンジル14.4ｇ（0.38当量）を滴下し、
混合物をそのまま１時間撹拌する。ゆつくり温度
を上げて20℃で15時間、そして70℃で２時間反応
させる。反応混合物をトルエンで抽出し、以後実
施例１と同様に操作して粗製の３，５，６−トリ
−Ｏ−ベンジル−１，２−Ｏ−イソプロピリデン
−α−Ｄ−グルコフラノース55ｇを得る。純度
83.4％（収率93.6％）。Example 4 22 g of 1,2-O-isopropylidene-α-D-glucofuranose was added to N-methyl-2-pyrrolidone.
Dissolve in 132 ml [6 times (v/w)], add 10.6 g (0.84 equivalents) of powdered sodium hydroxide and stir for 1 hour. After dropping 31 g (0.82 eq.) of benzyl chloride and stirring for 1 hour, 8.3 g (0.66 eq.) of powdered sodium hydroxide is added. Cool to below 10°C, add 14.4g (0.38 equivalents) of benzyl chloride dropwise,
The mixture is left to stir for 1 hour. Slowly raise the temperature and react at 20℃ for 15 hours and then at 70℃ for 2 hours. The reaction mixture was extracted with toluene, and then the same procedure as in Example 1 was performed to obtain 55 g of crude 3,5,6-tri-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose. . purity
83.4% (yield 93.6%).
なお粗生成物中に含まれる５，６−ジ−Ｏ−ベ
ンジル−１，２−Ｏ−イソプロピリデン−α−Ｄ
−グルコフラノースは0.13％であり、また３，６
−ジ−Ｏ−ベンジル−１，２−Ｏ−イソプロピリ
デン−α−Ｄ−グルコフラノースは0.29％であ
る。 Furthermore, 5,6-di-O-benzyl-1,2-O-isopropylidene-α-D contained in the crude product
- Glucofuranose is 0.13% and also 3,6
-di-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose is 0.29%.
比較例
１，２−Ｏ−イソプロピリデン−α−Ｄ−グル
コフラノース300ｇをDMSO1.7に溶解し粉末水
酸化ナトリウム258ｇを加えて30℃で１時間撹拌
する。塩化ベンジル617ｇを滴下し、室温で更に
一夜撹拌した。反応物をトルエンで抽出し、抽出
液を水及び飽和食塩水で順次あらつたあと、無水
硫酸ナトリウムで乾燥する。溶媒を減圧留去して
３，５，６−トリ−Ｏ−ベンジル−１，２−Ｏ−
イソプロピリデン−α−Ｄ−グルコフラノース
757ｇを得た。純度83.8％（収率94.9％）。Comparative Example 300 g of 1,2-O-isopropylidene-α-D-glucofuranose was dissolved in 1.7 DMSO, 258 g of powdered sodium hydroxide was added, and the mixture was stirred at 30°C for 1 hour. 617 g of benzyl chloride was added dropwise, and the mixture was further stirred at room temperature overnight. The reaction product is extracted with toluene, and the extract is washed with water and saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to give 3,5,6-tri-O-benzyl-1,2-O-
Isopropylidene-α-D-glucofuranose
Obtained 757g. Purity 83.8% (yield 94.9%).
なお粗生成物中に含まれる５，６−ジ−Ｏ−ベ
ンジル−１，２−Ｏ−イソプロピリデン−α−Ｄ
−グルコフラノースは２，４％であり、また３，
６−ジ−Ｏ−ベンジル−１，２−Ｏ−イソプロピ
リデン−α−Ｄ−グルコフラノースは2.6％であ
る。 Furthermore, 5,6-di-O-benzyl-1,2-O-isopropylidene-α-D contained in the crude product
- Glucofuranose is 2.4% and 3.
6-di-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose is 2.6%.
参考例１ （特公昭36−23319の方法）
１，２−Ｏ−イソプロピリデン−α−Ｄ−グル
コフラノース4.4ｇと塩化ベンジル25.3ｇ（3.35当
量）の混合物を90゜で撹拌し、粉末水酸化カリウ
ム14ｇ（3.54当量）を徐々に加える。90℃で５時
間反応した後、冷却しトルエンで抽出を行ない、
以後実施例１と同様に処理すると粗製の３，５，
６−トリ−Ｏ−ベンジル−１，２−Ｏ−イソプロ
ピリデン−α−Ｄ−グルコフラノース27.0ｇを得
る。純度30.7％。Reference Example 1 (Method of Japanese Patent Publication No. 36-23319) A mixture of 4.4 g of 1,2-O-isopropylidene-α-D-glucofuranose and 25.3 g (3.35 equivalents) of benzyl chloride was stirred at 90° and powdered hydroxylated. Gradually add 14 g (3.54 equivalents) of potassium. After reacting at 90°C for 5 hours, it was cooled and extracted with toluene.
Thereafter, the same treatment as in Example 1 yields crude 3, 5,
27.0 g of 6-tri-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose are obtained. Purity 30.7%.
なお粗生成物中に含まれる５，６−ジ−Ｏ−ベ
ンジル−１，２−Ｏ−イソプロピリデン−α−Ｄ
−グルコフラノースは4.91％であり、また３，６
−ジ−Ｏ−ベンジル−１，２−Ｏ−イソプロピリ
デン−α−Ｄ−グルコフラノースは0.50％であ
る。 Furthermore, 5,6-di-O-benzyl-1,2-O-isopropylidene-α-D contained in the crude product
- Glucofuranose is 4.91% and also 3,6
-di-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose is 0.50%.
参考例２ 〔「Helv」51，1185（1968）の方法〕
１，２−Ｏ−イソプロピリデン−α−Ｄ−グル
コフラノース4.4ｇをジオキサン10ml中に加え、
40゜で撹拌しつつ粉末水酸化カリウム6.7ｇ（1.7当
量）を加える。温度を90゜に上げ、塩化ベンジル
12.7ｇ（1.68当量）を滴下し、さらに５時間反応
させる。以後実施例１と同様に処理すると粗製の
３，５，６−トリ−Ｏ−ベンジル−１，２−Ｏ−
イソプロピリデン−α−Ｄ−グルコフラノース
14.4ｇを得る。純度56.5％。Reference Example 2 [Method of "Helv" 51 , 1185 (1968)] Add 4.4 g of 1,2-O-isopropylidene-α-D-glucofuranose to 10 ml of dioxane,
While stirring at 40°, add 6.7 g (1.7 equivalents) of powdered potassium hydroxide. Raise the temperature to 90° and add benzyl chloride.
12.7 g (1.68 equivalents) was added dropwise and the reaction was continued for an additional 5 hours. Thereafter, treatment was carried out in the same manner as in Example 1 to obtain crude 3,5,6-tri-O-benzyl-1,2-O-
Isopropylidene-α-D-glucofuranose
Obtain 14.4g. Purity 56.5%.
なお粗生成物中に含まれる５，６−ジ−Ｏ−ベ
ンジル−１，２−Ｏ−イソプロピリデン−α−Ｄ
−グルコフラノースは10.73％であり、また３，
６−ジ−Ｏ−ベンジル−１，２−Ｏ−イソプロピ
リデン−α−Ｄ−グルコフラノースは10.9％であ
る。 Furthermore, 5,6-di-O-benzyl-1,2-O-isopropylidene-α-D contained in the crude product
- Glucofuranose is 10.73% and 3,
6-di-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose is 10.9%.
Claims (1)
ルコフラノースを該グルコフラノース１当量当た
り約1.1〜1.3当量の塩化ベンジルを用いて非プロ
トン性極性溶媒中でベンジル化するにあたり、第
１段階で全当量の約2/3の塩化ベンジルを用いて
室温ないし70℃の温度でベンジル化しさらに第２
段階で全当量の約1/3の塩化ベンジルを用いて０
ないし10℃の温度でベンジル化することを特徴と
する、３，５，６−トリ−Ｏ−ベンジル−１，２
−Ｏ−イソプロピリデン−α−Ｄ−グルコフラノ
ースの製造法。1 In the first step of benzylating 1,2-O-isopropylidene-α-D-glucofuranose using about 1.1 to 1.3 equivalents of benzyl chloride per equivalent of the glucofuranose in an aprotic polar solvent. Benzylation using about 2/3 of the total equivalent of benzyl chloride at a temperature of room temperature to 70°C, followed by a second reaction.
0 using about 1/3 of the total equivalent of benzyl chloride in step
3,5,6-tri-O-benzyl-1,2, characterized in that it is benzylated at a temperature of from 10°C to 10°C.
A method for producing -O-isopropylidene-α-D-glucofuranose.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4017182A JPS58157797A (en) | 1982-03-16 | 1982-03-16 | Preparation of 3,5,6-tri-o-benzyl-1,2-o-isopropylidene-alpha-d- glucofuranose |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4017182A JPS58157797A (en) | 1982-03-16 | 1982-03-16 | Preparation of 3,5,6-tri-o-benzyl-1,2-o-isopropylidene-alpha-d- glucofuranose |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58157797A JPS58157797A (en) | 1983-09-19 |
| JPH024234B2 true JPH024234B2 (en) | 1990-01-26 |
Family
ID=12573314
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4017182A Granted JPS58157797A (en) | 1982-03-16 | 1982-03-16 | Preparation of 3,5,6-tri-o-benzyl-1,2-o-isopropylidene-alpha-d- glucofuranose |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS58157797A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104387428A (en) * | 2014-12-09 | 2015-03-04 | 济南卡博唐生物科技有限公司 | Method for preparing 3,5,6-tri-oxy-benzyl-1,2-isopropylidene-D-glucose |
| CN104478955A (en) * | 2014-12-09 | 2015-04-01 | 济南卡博唐生物科技有限公司 | Preparation method of 3, 5, 6-tri-oxo-benzyl-1, 2-isopropylidene-D-glucose |
-
1982
- 1982-03-16 JP JP4017182A patent/JPS58157797A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS58157797A (en) | 1983-09-19 |
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