JPS5874645A - Preparation of dl-norleucine - Google Patents
Preparation of dl-norleucineInfo
- Publication number
- JPS5874645A JPS5874645A JP17286281A JP17286281A JPS5874645A JP S5874645 A JPS5874645 A JP S5874645A JP 17286281 A JP17286281 A JP 17286281A JP 17286281 A JP17286281 A JP 17286281A JP S5874645 A JPS5874645 A JP S5874645A
- Authority
- JP
- Japan
- Prior art keywords
- norleucine
- halobutylhydantoin
- delta
- reaction
- butylhydantoin
- 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
- LRQKBLKVPFOOQJ-UHFFFAOYSA-N 2-aminohexanoic acid Chemical compound CCCCC(N)C(O)=O LRQKBLKVPFOOQJ-UHFFFAOYSA-N 0.000 title description 8
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- NOHNSECEKFOVGT-UHFFFAOYSA-N 1-butylimidazolidine-2,4-dione Chemical compound CCCCN1CC(=O)NC1=O NOHNSECEKFOVGT-UHFFFAOYSA-N 0.000 claims 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract description 18
- 229910000564 Raney nickel Inorganic materials 0.000 abstract description 5
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 abstract description 5
- 238000010531 catalytic reduction reaction Methods 0.000 abstract description 5
- JZBMVRBRZUZZCT-UHFFFAOYSA-N 5-butylimidazolidine-2,4-dione Chemical compound CCCCC1NC(=O)NC1=O JZBMVRBRZUZZCT-UHFFFAOYSA-N 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 3
- 239000003513 alkali Substances 0.000 abstract description 2
- 230000003115 biocidal effect Effects 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract 2
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 abstract 1
- 239000003242 anti bacterial agent Substances 0.000 abstract 1
- 239000000470 constituent Substances 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000000034 method Methods 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 235000011121 sodium hydroxide Nutrition 0.000 description 5
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- TWRKXHFCQVEYHI-UHFFFAOYSA-N 5-(4-bromobutyl)imidazolidine-2,4-dione Chemical compound BrCCCCC1NC(=O)NC1=O TWRKXHFCQVEYHI-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- ZKHLVOULDIXSCC-UHFFFAOYSA-N 5-(4-chlorobutyl)imidazolidine-2,4-dione Chemical compound ClCCCCC1NC(=O)NC1=O ZKHLVOULDIXSCC-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 2
- 238000005695 dehalogenation reaction Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
- -1 5-δ-iodobutylhydantoin Chemical compound 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 235000019454 L-leucine Nutrition 0.000 description 1
- 239000004395 L-leucine Substances 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229910045601 alloy Inorganic materials 0.000 description 1
- 239000000956 alloy Substances 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229960003136 leucine Drugs 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
本発明はＤＬ−ノルロイシンの新規製造方法に関するも
のである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing DL-norleucine.
ＤＬ−ノルロイシンはその光学異性体Ｌ−ノルロイシン
が抗性物質ＤＯＮ（ｅ−ジアゾ−５−オキシ−Ｌ−ノル
ロイシン）の構成成分であり、また、細菌の生育におい
て、Ｌ−ロイシンに対し拮抗作用を有するアミノ酸であ
る。ＤＬ−ノルロイシンの公知の合成方法としては、α
−プロモーｎ−カプロン酸をアンモニア水と反応させる
方法（Ｏｒｇ、 Ｓｙｎ、、 ４巻、：う頁、 １９２
５年）、アゼト了Ｊミゾシアｌ酢酸工、チルを臭化ブチ
ルと反応させた後、加水分解する方法（Ｊ、 Ｐｈａｒ
ｍ。DL-norleucine, whose optical isomer L-norleucine is a component of the antibiotic substance DON (e-diazo-5-oxy-L-norleucine), also has an antagonistic effect on L-leucine during bacterial growth. It is an amino acid with Known methods for synthesizing DL-norleucine include α
- Method for reacting promo n-caproic acid with aqueous ammonia (Org, Syn, Vol. 4, p. 192
5 years), a method of reacting acetic acid with butyl bromide and then hydrolyzing it (J, Phar
m.
Ｓｏｃ、 Ｊａｐａｎ、 ６８巻、２２６頁、 １９
４８年）、マロン酸誘導体を用いる方法等、数種類の合
成方法が知られているが、原料の入手の困難さや工程の
繁雑さ等、いずれも工業的に有利な方法とは言えない。Soc, Japan, vol. 68, p. 226, 19
Although several types of synthesis methods are known, such as a method using a malonic acid derivative (48), none of them can be said to be industrially advantageous due to the difficulty in obtaining raw materials and the complexity of the process.
そこで本発明者らは、鋭意検討の結果、８，４−ジヒド
ロ−２Ｈ−ピランより、容易に合成される５−δ−ハロ
ブチルヒダントインを脱ハロゲン化後、加水分、解駿て
収率よくＤＬ−ノルロイシンが得られる事を知見し２本
発明を完成した。As a result of intensive studies, the present inventors have determined that 5-δ-halobutylhydantoin, which is easily synthesized from 8,4-dihydro-2H-pyran, can be dehalogenated, hydrolyzed, and decomposed in a high yield. They discovered that DL-norleucine can be obtained and completed the present invention.
本発明を化学反応式を以て表わせば下式のとおりである
。The present invention can be expressed as a chemical reaction formula as shown below.
０ ０
ＣＨａ（ＣＬ）ｍ ＣＨ−ＣＯｔＨ
ＮＨ。0 0
CHa(CL)mCH-COtHNH.
（式中Ｘは０１．Ｂｒ、Ｉを表わす） ５−δ−ハロブチルヒダントインとしては。(In the formula, X represents 01.Br, I) As 5-δ-halobutylhydantoin.
５−δ−クロロブチルヒダントイン、５−δ−・ブロモ
ブチルヒダントイン、５−δ−ヨードブチルヒダントイ
ンの何れも使用することができるが、５−δ−ブロモブ
チルヒダントインを原料とした場合、脱ハロゲン化反応
が容易に進行し、収率よ＜、ＤＬ−ノルロイシンを得る
ことが出来る。脱ハロゲン化反応についてはパラジウム
・炭素、ラネーニッケル触媒による接触還元、 Ｎａ
ＢＩ３．亜鉛宋還元等、何れの方法を用いても反応は進
行するが、触媒の価格や、水溶液中で反応できる点でラ
ネーニッケル触媒による接触還元が好ましいと考える。Any of 5-δ-chlorobutylhydantoin, 5-δ-bromobutylhydantoin, and 5-δ-iodobutylhydantoin can be used, but when 5-δ-bromobutylhydantoin is used as a raw material, dehalogenation The reaction proceeds easily and DL-norleucine can be obtained in a high yield. For dehalogenation reaction, palladium/carbon, catalytic reduction using Raney nickel catalyst, Na
BI3. The reaction proceeds no matter which method is used, such as zinc reduction, but catalytic reduction using a Raney nickel catalyst is considered preferable because of the cost of the catalyst and the fact that the reaction can be carried out in an aqueous solution.
加水分解反応は。What is the hydrolysis reaction?
過剰のアルカリ、好ましくは２〜８倍モルの苛性ソーダ
を用いてオートクレーブ中で１００〜２００℃の範囲で
行うのが良い。次に実施例を挙げて本発明を説明する。It is preferable to carry out the reaction in an autoclave at a temperature of 100 to 200°C using an excess of alkali, preferably 2 to 8 times the molar amount of caustic soda. Next, the present invention will be explained with reference to Examples.
実施例１．
５−δ−ブロモブチルヒダントイン４０ ｋｇ（１７０
モル）を水１２０１に懸濁し、冷却下、５０％苛性ソー
ダ水溶液２８に９（８５０モル）を添加した。結晶が溶
解した後、接触還元装置に吸い上げ、展開したラネーニ
ッケル触媒を加えて、水素ガスを通じ、接触還元を行っ
た。８時間で予定量の水素を消費し、吸収が止まったの
で反応終了とした。触媒を濾過して除いた後、Ｐ液を濃
塩酸で中和して析出した白色粉末結晶を濾過し、５−ブ
チルヒダントイン２２９に９を得た。これは理論量の８
６％に相当する。Example 1. 5-δ-bromobutylhydantoin 40 kg (170
mol) was suspended in water 1201, and 9 (850 mol) was added to 50% caustic soda aqueous solution 28 while cooling. After the crystals were dissolved, they were sucked up into a catalytic reduction device, the developed Raney nickel catalyst was added, and hydrogen gas was passed through to perform catalytic reduction. The expected amount of hydrogen was consumed in 8 hours and absorption stopped, so the reaction was terminated. After removing the catalyst by filtration, the P solution was neutralized with concentrated hydrochloric acid, and the precipitated white powder crystals were filtered to obtain 5-butylhydantoin 229 and 9. This is the theoretical quantity 8
This corresponds to 6%.
融点 １８９〜１４０℃。Melting point: 189-140°C.
５−ブチルヒダントイン２２．９７Ｃ９（１４７モル）
を水１００１，５０％苛性ソーダ水溶液８５．２ｋ（ｉ
（４４０モル）に溶解し、オートクレーブ中１４０℃で
４時間攪拌して反応を完結させた０反応液を濃縮した後
、濃塩酸で中和して析出した白色粉末結晶を濾過し、Ｄ
Ｌ−ノルロイシンの粗晶１５．２Ｉｃｇを得た。これは
理論量の７９％に相当する０融点 ２７７〜２７９℃（
分解）。5-Butylhydantoin 22.97C9 (147 mol)
water 1001, 50% caustic soda aqueous solution 85.2k (i
(440 mol) and stirred in an autoclave at 140°C for 4 hours to complete the reaction. After concentrating the reaction solution, it was neutralized with concentrated hydrochloric acid and the precipitated white powder crystals were filtered.
15.2 Icg of crude crystals of L-norleucine were obtained. This corresponds to 79% of the theoretical amount with a melting point of 277-279℃ (
Disassembly).
粗晶のＤＬ−ノルロイシンを水２５倍量で再結晶して白
色鱗片具のＤＬ−フルロイシンを得た。融点 ２８５℃
（分解）。Crude crystal DL-norleucine was recrystallized with 25 times the amount of water to obtain white scaly DL-fluleucine. Melting point 285℃
(Disassembly).
実施例２゜
５−δ−クロロブチルヒダントイン１９．１％（０，１
モル）を水２００ ｍｌ、 ５６％苛性ソーダ水溶液９
．６ｐ（０，１２モル）に溶解し、ラネーニッケル合金
２０１と５０％苛性ソーダ水溶液８０１を４時間かけて
少量ずつ添加した。Example 2 5-δ-chlorobutylhydantoin 19.1% (0,1
200 ml of water, 56% caustic soda aqueous solution 9
．． Raney nickel alloy 201 and 50% caustic soda aqueous solution 801 were added little by little over 4 hours.
触媒を濾過後、Ｐ液に濃塩酸を加えてｐＨ＋１とし、析
出した白色粉末品を濾過し、５−ブチルヒダントイン１
１．５ｐを得た０収率７４％。After filtering the catalyst, add concentrated hydrochloric acid to the P solution to adjust the pH to +1, filter the precipitated white powder, and remove 5-butylhydantoin 1.
0 yield 74% yielding 1.5p.
融点 １８７〜１８９℃。Melting point: 187-189°C.
以下実施例１と同様に操作し、ＤＬ−ノルロイシンを得
た。Thereafter, the same procedure as in Example 1 was carried out to obtain DL-norleucine.
Claims (1)
ブチルヒダントインとし、これを加水分解することを特
徴とするＤＬ−フルロイシンの製造法。5-δ-Halobutylhydantoin is dehalogenated to give 5-
A method for producing DL-fluleucine, which comprises using butylhydantoin and hydrolyzing it.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17286281A JPS5874645A (en) | 1981-10-30 | 1981-10-30 | Preparation of dl-norleucine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17286281A JPS5874645A (en) | 1981-10-30 | 1981-10-30 | Preparation of dl-norleucine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS5874645A true JPS5874645A (en) | 1983-05-06 |
Family
ID=15949667
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP17286281A Pending JPS5874645A (en) | 1981-10-30 | 1981-10-30 | Preparation of dl-norleucine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5874645A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6256457A (en) * | 1985-09-05 | 1987-03-12 | Mitsui Toatsu Chem Inc | Production of n-acetyl-dl-amino acid |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5521734A (en) * | 1978-08-01 | 1980-02-16 | Takuya Okada | Attachable apparatus of extending and retracting fishing rod |
-
1981
- 1981-10-30 JP JP17286281A patent/JPS5874645A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5521734A (en) * | 1978-08-01 | 1980-02-16 | Takuya Okada | Attachable apparatus of extending and retracting fishing rod |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6256457A (en) * | 1985-09-05 | 1987-03-12 | Mitsui Toatsu Chem Inc | Production of n-acetyl-dl-amino acid |
| JPH0623148B2 (en) * | 1985-09-05 | 1994-03-30 | 三井東圧化学株式会社 | Method for producing N-acetyl-DL-amino acid |
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