JPH03118354A - Production of aspartic acid 4-benzyl ester - Google Patents
Production of aspartic acid 4-benzyl esterInfo
- Publication number
- JPH03118354A JPH03118354A JP25622789A JP25622789A JPH03118354A JP H03118354 A JPH03118354 A JP H03118354A JP 25622789 A JP25622789 A JP 25622789A JP 25622789 A JP25622789 A JP 25622789A JP H03118354 A JPH03118354 A JP H03118354A
- Authority
- JP
- Japan
- Prior art keywords
- aspartic acid
- benzyl ester
- base
- aspartyl
- salt
- 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
- VGALFAWDSNRXJK-VIFPVBQESA-N L-aspartic acid beta-benzyl ester Chemical compound OC(=O)[C@@H](N)CC(=O)OCC1=CC=CC=C1 VGALFAWDSNRXJK-VIFPVBQESA-N 0.000 title claims description 9
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- BQAMWLOABQRMAO-INIZCTEOSA-N dibenzyl (2s)-2-aminobutanedioate Chemical compound C([C@H](N)C(=O)OCC=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 BQAMWLOABQRMAO-INIZCTEOSA-N 0.000 claims abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 5
- 239000002585 base Substances 0.000 claims description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 abstract description 8
- 150000001875 compounds Chemical class 0.000 abstract description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Substances [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 abstract description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 abstract description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 abstract description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 abstract description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 4
- 239000005749 Copper compound Substances 0.000 abstract description 3
- 150000001880 copper compounds Chemical class 0.000 abstract description 3
- 239000000203 mixture Substances 0.000 abstract description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 abstract description 2
- 230000003266 anti-allergic effect Effects 0.000 abstract description 2
- 235000003704 aspartic acid Nutrition 0.000 abstract description 2
- 235000019445 benzyl alcohol Nutrition 0.000 abstract description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 abstract description 2
- 239000003960 organic solvent Substances 0.000 abstract description 2
- 229920001184 polypeptide Polymers 0.000 abstract description 2
- 102000004196 processed proteins & peptides Human genes 0.000 abstract description 2
- 108090000765 processed proteins & peptides Proteins 0.000 abstract description 2
- NJSRYBIBUXBNSW-VIFPVBQESA-N (3s)-3-azaniumyl-4-oxo-4-phenylmethoxybutanoate Chemical compound [O-]C(=O)C[C@H]([NH3+])C(=O)OCC1=CC=CC=C1 NJSRYBIBUXBNSW-VIFPVBQESA-N 0.000 abstract 1
- -1 aspartyl-seryl-aspartyl-prolyl- arginyl Chemical group 0.000 abstract 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 abstract 1
- 239000002994 raw material Substances 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229910000365 copper sulfate Inorganic materials 0.000 description 3
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- KQDIGHIVUUADBZ-PEDHHIEDSA-N pentigetide Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O KQDIGHIVUUADBZ-PEDHHIEDSA-N 0.000 description 1
- 239000002244 precipitate Substances 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、アスパラギン酸４−ベンジルエステルの新規
製法に関する。DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to a novel method for producing aspartic acid 4-benzyl ester.
（従来技術）
アスパラギン酸４−ベンジルエステルは、医薬化合物の
合成中間体として有用な化合物であり、たとえば優れた
抗アレルギー作用を有するポリペプチドであるアスパル
チル−セリル−アスパルチル−プロリル−アルギニン等
（特公昭６０の中間原料として有用である。(Prior art) Aspartic acid 4-benzyl ester is a compound useful as a synthetic intermediate for pharmaceutical compounds, such as aspartyl-seryl-aspartyl-prolyl-arginine, which is a polypeptide with excellent antiallergic effects (Tokuko Showa). 60 is useful as an intermediate raw material.
従来１．アスパラギン酸４−ベンジルエステルの製法と
しては、アスパラギン酸ジベンジルエステルを硫酸銅の
存在下、水酸化ナトリウムで加水分解し、得られる錯体
をエチレンジアミン四酢酸で分解する方法〔ジャーナル
・オン・オルガニック・ケミストリー、第４０巻、３２
８７頁、（１９７５年〕〕が知られている。しかしなが
ら、この方法は、製造工程が複雑で、銅化合物の環境へ
の影響や使用後の処理などに対し配慮が必要であった。Conventional 1. As a method for producing aspartic acid 4-benzyl ester, aspartic acid dibenzyl ester is hydrolyzed with sodium hydroxide in the presence of copper sulfate, and the resulting complex is decomposed with ethylenediaminetetraacetic acid [Journal on Organic Chemistry, Volume 40, 32
87, (1975)].However, this method requires a complicated manufacturing process, and requires consideration of the environmental impact of the copper compound and its treatment after use.
（発明の構成及び効果）
本発明によれば、アスパラギン酸４−ベンジルエステル
は、アスパラギン酸ジベンジルエステルを、塩基を用い
て部分加水分解することによって製造することができる
。(Structure and effects of the invention) According to the present invention, aspartic acid 4-benzyl ester can be produced by partially hydrolyzing aspartic acid dibenzyl ester using a base.
当該加水分解は、例えばテトラヒドロフラン、アセトン
、ジオキサン、メタノール、エタノール等の有機溶媒と
水との混合溶媒中０℃〜室温、とりわけ０〜１５°Ｃで
好適に実施することができる。The hydrolysis can be suitably carried out, for example, in a mixed solvent of water and an organic solvent such as tetrahydrofuran, acetone, dioxane, methanol, or ethanol at a temperature of 0°C to room temperature, particularly 0 to 15°C.
２３１８号）
原料化合物であるアスパラギン酸ジベンジルエステルは
、遊離のまま或いは塩のいずれの形ででも用いることが
でき、かかる塩としては、例えば塩酸塩、硫酸塩等の無
機酸付加塩又はＰ−Ｉ−ルエンスルホン酸塩、メタンス
ルホン酸塩等の有機酸付加塩等を好適に使用することが
できる。No. 2318) Aspartic acid dibenzyl ester, which is a raw material compound, can be used either as a free form or in the form of a salt. Such salts include, for example, inorganic acid addition salts such as hydrochloride and sulfate, or P- Organic acid addition salts such as I-luenesulfonate and methanesulfonate can be suitably used.
塩基としては、例えば水酸化ナトリウム、水酸化カリウ
ム等を好適に使用することができ、その使用量は、通常
、原料化合物に対して１．８〜２．４倍モル量、特に２
．０〜２．２倍モル量であるのが好ましい。As the base, sodium hydroxide, potassium hydroxide, etc. can be suitably used, and the amount used is usually 1.8 to 2.4 times the molar amount of the raw material compound, especially 2.
．． The amount is preferably 0 to 2.2 times the molar amount.
上記本発明方法は、取り扱いに配慮を要する銅化合物（
硫酸銅）を使用せず、操作が簡便であるという利点が得
られることから、アスパラギン酸４−ベンジルエステル
の工業的に有利な製法となるものである。The method of the present invention described above is applicable to copper compounds (
This method is an industrially advantageous method for producing aspartic acid 4-benzyl ester because it does not use copper sulfate (copper sulfate) and is easy to operate.
尚、本発明の原料化合物であるアスパラギン酸ジベンジ
ルエステルは、例えば日本化学雑誌、第７８巻、１７６
８頁、（１９５７年）記載方法に準じ、アスパラギン酸
とベンジルアルコールとから製造することができる。Note that aspartic acid dibenzyl ester, which is a raw material compound of the present invention, is described, for example, in Nippon Kagaku Zasshi, Vol. 78, 176.
It can be produced from aspartic acid and benzyl alcohol according to the method described on page 8 (1957).
実施例Ｉ
Ｌ−アスパラギン酸ジベンジルエステル・Ｉ）−トルエ
ンスルホン酸塩７２．８ｇをテトラヒドロフラン２９０
成と水２２０ｍβとの混液に溶解する。該溶液に、２０
％水酸化す］・リウム水溶液６６ｇを１３°Ｃで滴下し
た後、３０分間撹拌する。反応液をクロロホルム１５０
１ｄで洗浄し、１５°Ｃで１０％塩酸を滴下してｐＨ４
〜５とした後、析出品をろ取することによりＬ−アスパ
ラギン酸４−ベンジルエステル２０．７ｇを得る。 収
率： ６２．２％ｍ、 Ｐ、 ２１３〜２１５”Ｃ
（α） ｎ ＋２７． ２° （Ｃ＝１．ＩＮ塩酸）実
施例２
Ｌ−アスパラギン酸ジベンジルエステル・ｐ−トルエン
スルホン酸塩４８．６ｇを、水酸化ナトリウムに代えて
水酸化カリウムを用いる以外は実施例１と同様に処理す
ることにより、し−アスパラギン酸４−ベンジルエステ
ル１４．７ｇを得る。Example I 72.8 g of L-aspartic acid dibenzyl ester I)-toluenesulfonate was dissolved in 290 g of tetrahydrofuran.
Dissolved in a mixture of 220 mβ of water and 220 mβ of water. To the solution, add 20
% hydroxide]-lium aqueous solution was added dropwise at 13°C, and the mixture was stirred for 30 minutes. The reaction solution was diluted with 150% chloroform.
Wash with 1d and add 10% hydrochloric acid dropwise at 15°C to pH 4.
5, and then filtering the precipitate to obtain 20.7 g of L-aspartic acid 4-benzyl ester. Yield: 62.2% m. By treating .6 g in the same manner as in Example 1 except using potassium hydroxide instead of sodium hydroxide, 14.7 g of 4-benzyl aspartic acid ester was obtained.
収率： ６５．７％
実施例３
Ｌ−アスパラギン酸ジベンジルエステル・ｐ−）ルエン
スルホン酸塩１２．８ｇを、テトラヒドロフランに代え
てアセトンを用いる以外は実施例１と同様に処理するこ
とにより、 Ｌ−アスパラギン酸４−ベンジルエステル
２２．１ｇを１％る。Yield: 65.7% Example 3 12.8 g of L-aspartic acid dibenzyl ester/p-)luenesulfonate was treated in the same manner as in Example 1 except that acetone was used instead of tetrahydrofuran. 22.1 g of L-aspartic acid 4-benzyl ester was added at 1%.
収率： ６５．９％Yield: 65.9%
Claims (2)
、塩基で部分加水分解することを特徴とするアスパラギ
ン酸４−ベンジルエステル又はその塩の製法。(1) A method for producing aspartic acid 4-benzyl ester or its salt, which comprises partially hydrolyzing aspartic acid dibenzyl ester or its salt with a base.
製法。(2) The method according to claim 1, wherein the base is an alkali metal hydroxide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25622789A JPH03118354A (en) | 1989-09-29 | 1989-09-29 | Production of aspartic acid 4-benzyl ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25622789A JPH03118354A (en) | 1989-09-29 | 1989-09-29 | Production of aspartic acid 4-benzyl ester |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH03118354A true JPH03118354A (en) | 1991-05-20 |
Family
ID=17289704
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP25622789A Pending JPH03118354A (en) | 1989-09-29 | 1989-09-29 | Production of aspartic acid 4-benzyl ester |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH03118354A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6371886B1 (en) | 1998-10-30 | 2002-04-16 | Mazda Motor Corporation | Controller for automatic transmission |
| EP1391449A1 (en) * | 2002-08-09 | 2004-02-25 | PCBU Services, Inc. | Hydrolysis of amino acid diesters |
| US7891266B2 (en) | 2005-04-01 | 2011-02-22 | Toyota Jidosha Kabushiki Kaisha | Gear position display device of transmission |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2608174A1 (en) * | 1975-12-30 | 1977-07-14 | Pharmedical Sa Lab | Aspartyl (hydroxy)phenyl-alanine dipeptides prepn. - by hydrogenolysis of benzyl esters, for use as sweeteners |
-
1989
- 1989-09-29 JP JP25622789A patent/JPH03118354A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2608174A1 (en) * | 1975-12-30 | 1977-07-14 | Pharmedical Sa Lab | Aspartyl (hydroxy)phenyl-alanine dipeptides prepn. - by hydrogenolysis of benzyl esters, for use as sweeteners |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6371886B1 (en) | 1998-10-30 | 2002-04-16 | Mazda Motor Corporation | Controller for automatic transmission |
| EP1391449A1 (en) * | 2002-08-09 | 2004-02-25 | PCBU Services, Inc. | Hydrolysis of amino acid diesters |
| US7891266B2 (en) | 2005-04-01 | 2011-02-22 | Toyota Jidosha Kabushiki Kaisha | Gear position display device of transmission |
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