JPH0510338B2 - - Google Patents
Info
- Publication number
- JPH0510338B2 JPH0510338B2 JP59262913A JP26291384A JPH0510338B2 JP H0510338 B2 JPH0510338 B2 JP H0510338B2 JP 59262913 A JP59262913 A JP 59262913A JP 26291384 A JP26291384 A JP 26291384A JP H0510338 B2 JPH0510338 B2 JP H0510338B2
- Authority
- JP
- Japan
- Prior art keywords
- lysine
- anhydride
- acetic
- present
- 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
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 24
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 22
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 11
- BVHLGVCQOALMSV-JEDNCBNOSA-N L-lysine hydrochloride Chemical compound Cl.NCCCC[C@H](N)C(O)=O BVHLGVCQOALMSV-JEDNCBNOSA-N 0.000 claims description 11
- 235000019253 formic acid Nutrition 0.000 claims description 11
- 239000004472 Lysine Substances 0.000 claims description 9
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 9
- 229960003646 lysine Drugs 0.000 claims description 9
- 229960005337 lysine hydrochloride Drugs 0.000 claims description 8
- 150000007524 organic acids Chemical class 0.000 claims description 7
- LYUPJHVGLFETDG-UHFFFAOYSA-N 1-phenylbutan-2-ol Chemical compound CCC(O)CC1=CC=CC=C1 LYUPJHVGLFETDG-UHFFFAOYSA-N 0.000 claims description 5
- 229910052783 alkali metal Inorganic materials 0.000 claims description 5
- -1 alkali metal salt Chemical class 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 235000018977 lysine Nutrition 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- LIEIRDDOGFQXEH-LURJTMIESA-N (2s)-6-amino-2-formamidohexanoic acid Chemical compound NCCCC[C@@H](C(O)=O)NC=O LIEIRDDOGFQXEH-LURJTMIESA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 239000004280 Sodium formate Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- WFIZEGIEIOHZCP-UHFFFAOYSA-M potassium formate Chemical compound [K+].[O-]C=O WFIZEGIEIOHZCP-UHFFFAOYSA-M 0.000 description 3
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 3
- 235000019254 sodium formate Nutrition 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- JBBURJFZIMRPCZ-XRIGFGBMSA-N (2s)-2,6-diaminohexanoic acid;hydron;dichloride Chemical compound Cl.Cl.NCCCC[C@H](N)C(O)=O JBBURJFZIMRPCZ-XRIGFGBMSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- FQJRFMZNINFSOJ-SSDOTTSWSA-N (2r)-2,6-diamino-2-formylhexanoic acid Chemical compound NCCCC[C@@](N)(C=O)C(O)=O FQJRFMZNINFSOJ-SSDOTTSWSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- VGGRCVDNFAQIKO-UHFFFAOYSA-N formic anhydride Chemical compound O=COC=O VGGRCVDNFAQIKO-UHFFFAOYSA-N 0.000 description 1
- XKPJKVVZOOEMPK-UHFFFAOYSA-M lithium;formate Chemical compound [Li+].[O-]C=O XKPJKVVZOOEMPK-UHFFFAOYSA-M 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明はN2−ホルミルリジンの製造方法に関
するものである。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing N 2 -formyl lysine.
従来、N2−ホルミルリジンの製造方法として、
リジン−ギ酸塩を大過剰のギ酸に溶解した後、無
水酢酸10当量と反応させる方法が公知である〔ジ
ヤーナル オブ アメリカン ケミカル ソサイ
アテイ（Journal of American Chemical
Society）第82巻第3727ページ（1960）〕。
Conventionally, as a method for producing N 2 -formyl lysine,
A method is known in which lysine formate is dissolved in a large excess of formic acid and then reacted with 10 equivalents of acetic anhydride [Journal of American Chemical Society].
Society) Volume 82, Page 3727 (1960)].
この方法はリジンに二つ存在するアミノ基の
内、２位に存在するアミノ基だけを選択的に反応
せしめたN2−ホルミルリジンを得る方法として
は有用な方法ではあるが、98％以上の高い濃度の
ギ酸を使用しなければならないこと、しかも大過
剰に使用しなければならないこと、無水酢酸の使
用量が多いことならびに原料のリジン−ギ酸塩そ
のものの入手が困難で、従つて原料としては高価
であること等の問題がある。
Although this method is a useful method for obtaining N 2 -formyl lysine by selectively reacting only the amino group present at the 2-position of the two amino groups present in lysine, it is It is necessary to use a high concentration of formic acid, and in large excess, a large amount of acetic anhydride is used, and the raw material lysine-formate itself is difficult to obtain. There are problems such as being expensive.
そこで本発明者らは前記問題の解消を目的に検
討した結果、有機酸のアルカリ金属塩およびギ酸
の存在下で、リジン塩酸塩と無水酢酸および酢酸
ギ酸無水物から選ばれる有機酸無水物とを０〜20
℃で反応させることにより目的が達成され、効率
よくN2−ホルミルリジンが製造できることを見
いだし、本発明を完成した。
Therefore, the present inventors investigated with the aim of solving the above problem, and found that in the presence of an alkali metal salt of an organic acid and formic acid, lysine hydrochloride and an organic acid anhydride selected from acetic anhydride and acetic formic anhydride were combined. 0~20
The inventors have discovered that the objective can be achieved and N 2 -formyl lysine can be efficiently produced by reacting at a temperature of 0.degree. C., and the present invention has been completed.
以下、本発明の構成を説明する。 The configuration of the present invention will be explained below.
本発明に使用されるリジン塩酸塩とは、リジン
−塩酸塩、リジン二塩酸塩のいずれでもよいが、
好ましくはリジン−塩酸塩である。またそれらは
Ｄ体、Ｌ体またはラセミ体のいずれでも使用でき
る。 The lysine hydrochloride used in the present invention may be either lysine hydrochloride or lysine dihydrochloride, but
Preferred is lysine hydrochloride. Moreover, they can be used in any of the D-form, L-form or racemic form.
本発明において使用される有機酸のアルカリ金
属塩の好ましい具体例は、ギ酸ナトリウム、ギ酸
カリウム、ギ酸リチウム、酢酸ナトリウム、酢酸
カリウムであり、特に好ましくは、ギ酸ナトリウ
ムとギ酸カリウムである。 Preferred specific examples of the alkali metal salts of organic acids used in the present invention are sodium formate, potassium formate, lithium formate, sodium acetate, and potassium acetate, and particularly preferred are sodium formate and potassium formate.
有機酸のアルカリ金属塩の使用量はリジン塩酸
塩を中和するのに足りる量であればよく、例えば
リジン−塩酸塩ならば１当量であり、リジン二塩
酸塩であれば２当量あればよい。 The amount of alkali metal salt of an organic acid to be used may be an amount sufficient to neutralize lysine hydrochloride, for example, 1 equivalent for lysine hydrochloride and 2 equivalents for lysine dihydrochloride. .
ギ酸の使用量はリジンに対して５〜20当量、好
ましくは８〜11当量である。ギ酸使用量が５当量
未満であると、リジン塩酸塩や有機酸のアルカリ
金属塩が溶解せず反応収率が低くなる。また20当
量を越えると、反応には影響がないが、必要以上
の原料を使用することになる。なお、反応終了後
に反応系に残る未反応のギ酸は減圧蒸留して回収
し、再度使用することができる。 The amount of formic acid used is 5 to 20 equivalents, preferably 8 to 11 equivalents, relative to lysine. If the amount of formic acid used is less than 5 equivalents, lysine hydrochloride and the alkali metal salt of an organic acid will not dissolve, resulting in a low reaction yield. If the amount exceeds 20 equivalents, the reaction will not be affected, but more raw materials than necessary will be used. In addition, unreacted formic acid remaining in the reaction system after the completion of the reaction can be recovered by distillation under reduced pressure and used again.
無水酢酸の使用量はリジンに対して、１〜５倍
モル、好ましくは1.2〜３倍モルである。酢酸ギ
酸無水物の使用量はリジンに対して１〜４倍モ
ル、好ましくは1.1〜２倍モルである。 The amount of acetic anhydride used is 1 to 5 times the mole of lysine, preferably 1.2 to 3 times the mole of lysine. The amount of acetic formic anhydride used is 1 to 4 times the mole of lysine, preferably 1.1 to 2 times the mole of lysine.
反応時間は実質的に反応が終了するに十分な時
間をかければよいのであるが、通常は0.5〜2.0時
間である。 The reaction time may be sufficient to substantially complete the reaction, but is usually 0.5 to 2.0 hours.
反応温度は０〜20℃である。 The reaction temperature is 0-20°C.
反応が終了したら、反応液に水を加えて、無水
酢酸または酢酸ギ酸無水物を分解して酢酸、ギ酸
にした後にこれらの酸を減圧下で濃縮するか、そ
のまま減圧濃縮してN2−ホルミルリジンを取得
する。 After the reaction is completed, water is added to the reaction solution to decompose acetic anhydride or acetic formic anhydride into acetic acid and formic acid, and then these acids are concentrated under reduced pressure, or directly concentrated under reduced pressure to form N 2 -formyl. Get Lysine.
本発明法で得られたN2−ホルミルリジンはペ
プチドを合成するための原料として有効に利用さ
れる。 N2 -formyllysine obtained by the method of the present invention can be effectively used as a raw material for synthesizing peptides.
次に本発明の実施例を述べる。 Next, examples of the present invention will be described.
実施例 １
滴下ロート、温度計および攪拌器を装着した
500mlの３つ口フラスコにギ酸230.1ｇ（５モル）
およびＬ−リジン−塩酸塩91.3ｇ（0.5モル）を
仕込み、５〜10℃に冷却した。ギ酸ナトリウム
34.0ｇ（0.5モル）を10分間５〜10℃で加え、更
に30分間攪拌した。Example 1 Equipped with dropping funnel, thermometer and stirrer
230.1g (5 moles) of formic acid in a 500ml three-necked flask
and 91.3 g (0.5 mol) of L-lysine hydrochloride were charged and cooled to 5 to 10°C. sodium formate
34.0 g (0.5 mol) was added for 10 minutes at 5-10°C and stirred for an additional 30 minutes.
次いで無水酢酸102.1ｇ（1.0モル）を５〜10℃
にて30分間で滴下し、更に１時間、10〜20℃で攪
拌した。反応終了後、水10mlを加えてから室温で
１時間攪拌した。次いでエバポレータで減圧濃縮
した。濃縮物にエタノールを200ml加えて攪拌し
た後、冷蔵庫に一晩静置して結晶を析出させた。
得られた結晶を過分離して乾燥し、粗N2−ホ
ルミル−Ｌ−リジン80.2ｇを得た。収率は92.1％
であつた。エタノールで再結晶して精製された
N2−ホルミル−Ｌ−リジン（mp＝189〜191℃）
を得た。 Next, 102.1 g (1.0 mol) of acetic anhydride was heated at 5 to 10°C.
The mixture was added dropwise over 30 minutes and stirred for an additional hour at 10 to 20°C. After the reaction was completed, 10 ml of water was added and the mixture was stirred at room temperature for 1 hour. Then, it was concentrated under reduced pressure using an evaporator. After adding 200 ml of ethanol to the concentrate and stirring, the mixture was left standing in a refrigerator overnight to precipitate crystals.
The obtained crystals were separated and dried to obtain 80.2 g of crude N2 -formyl-L-lysine. Yield is 92.1%
It was hot. Purified by recrystallization with ethanol
N2 -formyl-L-lysine (mp=189-191℃)
I got it.
実施例 ２
実施例１と同様の装置にギ酸276.1ｇ（６モル）
およびＬ−リジン−塩酸塩91.3ｇ（0.5モル）を
仕込み、５〜10℃に冷却した。ギ酸カリウム42.1
ｇ（0.5モル）を10分間かけて加え、更に30分間
５〜10℃で攪拌した。Example 2 276.1 g (6 moles) of formic acid was placed in the same apparatus as in Example 1.
and 91.3 g (0.5 mol) of L-lysine hydrochloride were charged and cooled to 5 to 10°C. Potassium formate 42.1
g (0.5 mol) was added over 10 minutes and stirred for an additional 30 minutes at 5-10°C.
次いで酢酸ギ酸無水物57.2ｇ（0.65モル）を５
〜10℃にて30分間で滴下し、更に１時間10〜20℃
で攪拌した。反応終了後、水10mlを加えてから室
温で１時間攪拌した後、実施例１と同様にして粗
N2−ホルミルＬ−リジンを81.1ｇ取得した。収
率は93.1％であつた。 Next, 57.2 g (0.65 mol) of acetic formic anhydride was added to 5
Dropwise at ~10℃ for 30 minutes, then 1 hour at 10~20℃
It was stirred with After the reaction was completed, 10 ml of water was added and stirred at room temperature for 1 hour.
81.1 g of N 2 -formyl L-lysine was obtained. The yield was 93.1%.
本発明は次の効果を発揮する。 The present invention exhibits the following effects.
(1) 安価な原料であるＬ−リジン塩酸塩をそのま
ま使用しているので安価に本発明に係る化合物
を得ることができる。(1) Since L-lysine hydrochloride, which is an inexpensive raw material, is used as it is, the compound according to the present invention can be obtained at low cost.
(2) ギ酸や無水酢酸の使用量が少なくてよい。(2) The amount of formic acid and acetic anhydride used can be reduced.
(3) 酢酸・ギ酸無水物を使用した場合は更に安価
に本発明に係る化合物を得ることができる。(3) When acetic acid/formic anhydride is used, the compound according to the present invention can be obtained at a lower cost.
Claims (1)
で、リジン塩酸塩と無水酢酸および酢酸ギ酸無水
物から選ばれる有機酸無水物とを０〜20℃で反応
させることを特徴とするN2−ホルミルリジンの
製造方法。1 N2 -formyl, which is characterized by reacting lysine hydrochloride with an organic acid anhydride selected from acetic anhydride and acetic formic anhydride at 0 to 20°C in the presence of an alkali metal salt of an organic acid and formic acid. Method for producing lysine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59262913A JPS61140552A (en) | 1984-12-14 | 1984-12-14 | Production of n2-formyllysine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59262913A JPS61140552A (en) | 1984-12-14 | 1984-12-14 | Production of n2-formyllysine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61140552A JPS61140552A (en) | 1986-06-27 |
| JPH0510338B2 true JPH0510338B2 (en) | 1993-02-09 |
Family
ID=17382345
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59262913A Granted JPS61140552A (en) | 1984-12-14 | 1984-12-14 | Production of n2-formyllysine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61140552A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100377336B1 (en) * | 2000-11-17 | 2003-03-26 | 학교법인 카톨릭학원 | Method for the preparation of N-formyl-lysine and the analysis of glycation induced-protein crosslinking assay thereby |
-
1984
- 1984-12-14 JP JP59262913A patent/JPS61140552A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61140552A (en) | 1986-06-27 |
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