JPS6035358B2 - Method for producing pyroglutamylglycylamino acid - Google Patents
Method for producing pyroglutamylglycylamino acidInfo
- Publication number
- JPS6035358B2 JPS6035358B2 JP8288177A JP8288177A JPS6035358B2 JP S6035358 B2 JPS6035358 B2 JP S6035358B2 JP 8288177 A JP8288177 A JP 8288177A JP 8288177 A JP8288177 A JP 8288177A JP S6035358 B2 JPS6035358 B2 JP S6035358B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- moles
- pyroglutamic acid
- glycine
- alanine
- 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
Links
- 239000002253 acid Substances 0.000 title claims description 7
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 22
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 claims description 20
- ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 claims description 20
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 claims description 20
- 239000004471 Glycine Substances 0.000 claims description 11
- 235000001014 amino acid Nutrition 0.000 claims description 11
- 150000001413 amino acids Chemical class 0.000 claims description 11
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 10
- 235000013922 glutamic acid Nutrition 0.000 claims description 10
- 239000004220 glutamic acid Substances 0.000 claims description 10
- 238000010438 heat treatment Methods 0.000 claims description 6
- -1 glycylamino Chemical group 0.000 claims description 4
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 11
- 229940024606 amino acid Drugs 0.000 description 10
- 238000000034 method Methods 0.000 description 8
- 108010041049 pyroglutamylglycine Proteins 0.000 description 5
- HLPLTUJPJMFPMP-BYPYZUCNSA-N pyroglutamylglycine Chemical compound OC(=O)CNC(=O)[C@@H]1CCC(=O)N1 HLPLTUJPJMFPMP-BYPYZUCNSA-N 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 4
- 235000004279 alanine Nutrition 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 238000005580 one pot reaction Methods 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- CZNHSHCAPZFDAF-RYUDHWBXSA-N (2s)-3-(4-hydroxyphenyl)-2-[[2-[[(2s)-5-oxopyrrolidine-2-carbonyl]amino]acetyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)CNC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 CZNHSHCAPZFDAF-RYUDHWBXSA-N 0.000 description 2
- YIJVJUARZXCJJP-UHFFFAOYSA-N 2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoic acid Chemical compound OC(=O)C(C)NC(=O)C1CCC(=O)N1 YIJVJUARZXCJJP-UHFFFAOYSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000004570 mortar (masonry) Substances 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- ILJOYLTXYCZXTB-UHFFFAOYSA-N Pyroglu-tyr Chemical compound C1CC(=O)NC1C(=O)NC(C(=O)O)CC1=CC=C(O)C=C1 ILJOYLTXYCZXTB-UHFFFAOYSA-N 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 229940124277 aminobutyric acid Drugs 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Inorganic materials O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
Landscapes
- Peptides Or Proteins (AREA)
Description
【発明の詳細な説明】
本発明はトリベプチド更に詳しく言えばピログルタミル
グリシルアミノ酸の製造法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing tribeptide, and more particularly pyroglutamyl glycylamino acid.
本発明者等は別途、グルタミン酸（もしくはピログルタ
ミン酸）とこれと異る他のアミノ酸とを単に加熱するこ
とのみによって、単一種のピログルタミルベプチド形成
のみを行わしめ得ることを見出したが、かかる新知見に
加え、グルタミン酸（もしくはピログルタミン酸）とグ
リシンと、これらと異る他のアミノ酸とを三者の特定モ
ル比条件下に単に加熱すると、ピログルタミルグリシル
アミノ酸（トリベプチド）が一段階反応で効率良く得ら
れることを見出した。本発明はかかる新知見に基づき完
成されたものである。すなわち、本発明は、グルタミン
酸（もしくはピログルタミン酸）とグルシンとこれらと
異る他のアミノ酸とを１〜２：１：３〜５のモル比にお
いて、加熱することを特徴とするピログルタミルグリシ
ルアミノ酸の製造法を提供するものである。The present inventors have separately discovered that by simply heating glutamic acid (or pyroglutamic acid) and another amino acid different from glutamic acid, only a single type of pyroglutamyl peptide can be formed. In addition to the new findings, simply heating glutamic acid (or pyroglutamic acid), glycine, and other amino acids different from these at a specific molar ratio of the three results in a one-step reaction to form pyroglutamylglycylamino acid (tribeptide). We have found that this can be achieved efficiently. The present invention was completed based on this new knowledge. That is, the present invention provides a pyroglutamyl glycylamino acid, which is characterized in that glutamic acid (or pyroglutamic acid), glucine, and other amino acids different from these are heated in a molar ratio of 1 to 2:1:3 to 5. The present invention provides a method for manufacturing.
グルタミン酸（もしくはピログルタミン酸）とグリシン
の熱縮合反応においては、ピログルタミルグリシン（ジ
ベプチド）をはじめとして、ピログルタミルグリシルグ
リシン（トリベプチド）、ピログルタミルグリシルグリ
シルグリシン（テトラベプチド）まで生成するが、グル
タミン酸（もしくはピログルタミン酸）とグリシン以外
の他のアミノ酸との熱縮合反応においては、ピログルタ
ミルアミノ酸（ジベプチド）のみを生成し、この場合に
はトリベプチドやテトラベプチドは得られない。In the thermal condensation reaction of glutamic acid (or pyroglutamic acid) and glycine, pyroglutamylglycine (dibeptide), pyroglutamylglycylglycine (tribeptide), and pyroglutamylglycylglycylglycine (tetrabeptide) are produced, but glutamic acid ( In the thermal condensation reaction of pyroglutamic acid (or pyroglutamic acid) and other amino acids other than glycine, only pyroglutamyl amino acid (dipeptide) is produced, and in this case, tribeptide and tetrapeptide are not obtained.
本発明者等は、この２つの場合における異つた現象を利
用することにより、グルタミン酸（もしくはピログルタ
ミン酸）とグリシンと他の異なるアミノ酸とを特定のモ
ル比条件下に組み合わせ使用し、単なる加熱により、一
段階反応でピログルタミルグリシルアミノ酸（トリベプ
チド）を得ることに成功したものである。本発明方法に
おいては、原料であるグルタミン酸（もしくはピログル
タミン酸）、グリシンおよびこれと異るアミノ酸の他に
何等の添加成分（物質）例えば触媒等を用いる必要のな
いことが特徴的である。By utilizing the different phenomena in these two cases, the present inventors used glutamic acid (or pyroglutamic acid), glycine, and other different amino acids in combination under specific molar ratio conditions, and by mere heating, They succeeded in obtaining pyroglutamylglycylamino acid (tribeptide) in a one-step reaction. The method of the present invention is characterized in that there is no need to use any additional components (substances) such as catalysts in addition to the raw materials glutamic acid (or pyroglutamic acid), glycine, and amino acids different from these.
ただし、反応温度が低いとき少量の水の添加は反応開始
剤として効果的である。溶媒としては不活性溶媒を用い
ることは妨げないが、無溶媒が望ましい態様である。上
述の反応は不活性ガス例えば窒素、炭酸ガス雰囲気中で
行うのが好ましい。反応温度は通常８０〜２００ｏ○望
ましくは１３０〜１８０つ○である。反応中に発生する
水蒸気は連続的に取り除くことができるが、このことは
実施上必須の条件ではないが、原料として用いるグルタ
ミン酸は加熱により容易にピログルタミン酸となるため
、両者はいずれを用いても同一の結果をもたらす。本発
明方法で用いる前述の「他のアミノ酸」としてはアラニ
ン、バリン、。However, when the reaction temperature is low, the addition of a small amount of water is effective as a reaction initiator. Although it is possible to use an inert solvent as the solvent, it is preferable to use no solvent. The above reaction is preferably carried out in an atmosphere of an inert gas such as nitrogen or carbon dioxide. The reaction temperature is usually 80 to 200 degrees Celsius, preferably 130 to 180 degrees Celsius. The water vapor generated during the reaction can be continuously removed, but this is not an essential condition in practice, but since the glutamic acid used as a raw material can easily be converted to pyroglutamic acid by heating, it is possible to remove either of the two. yields the same result. Examples of the above-mentioned "other amino acids" used in the method of the present invention include alanine and valine.
イシン、イソロイシン、フヱニルアラニン、チロシン、
セリン、スレオニン、リジン、プロリン、ヒドロキシプ
ロリン、メチオニン、システイン、８−アラニン、Ｑー
アミノ酪酸、Ｑーアミノィソ酪酸、ｙーアミノ酪酸、ノ
ルバリン、ノルロィシン、サルコシンなど通常のアミノ
酸はすべてあげることができる。本発明方法の如く、３
種のアミノ酸を、単なる加熱により定められた順序でべ
プチド結合せしめて、トリベプチドを一段階反応で得る
という方法は、従来、全く知られておらず。またかかる
方法は全く予期し得ないものであった。しかも、操作が
簡単なばかりでなく、生成物も水溶液として、イオン交
換樹脂を通すことにより目的とするトリベプチドが容易
に分離、精製されるので、実用上も極めて優れた方法で
ある。Isine, isoleucine, phenylalanine, tyrosine,
All common amino acids such as serine, threonine, lysine, proline, hydroxyproline, methionine, cysteine, 8-alanine, Q-aminobutyric acid, Q-aminoisobutyric acid, y-aminobutyric acid, norvaline, norleucine, and sarcosine can be mentioned. As in the method of the present invention, 3
Conventionally, there has been no known method for obtaining tripeptides in a one-step reaction by bonding seed amino acids with peptides in a predetermined order by simply heating. Moreover, such a method was completely unexpected. Moreover, not only is the operation simple, but the target tripeptide can be easily separated and purified by passing the product as an aqueous solution through an ion exchange resin, so it is an extremely excellent method from a practical standpoint.
本発明方法により製造し得るピログルタミルグリシルア
ミノ酸類の中には、種々の有用性を有する物質や、種々
の用途に用いるべプチドの合成用中間原料がすべて包含
されるので、本発明方法の実用上の価値は極めて高いも
のである。以下に、本発明を実施例ならびに比較例によ
り説明するが、本発明は実施例により限定されるもので
はない。The pyroglutamyl glycylamino acids that can be produced by the method of the present invention include all substances with various usefulness and intermediate raw materials for the synthesis of peptides used for various purposes. Its practical value is extremely high. The present invention will be explained below using Examples and Comparative Examples, but the present invention is not limited by the Examples.
実施例 １
ピログルタミン酸３．２３夕（０．０２５モル）とグリ
シン０．９５夕（０．０１３モル）アラニン３．３５夕
（０．０３８モル）を乳鉢でよくすりつぶして混合し、
ガラス反応管でＮ２ガスを流しながら、１７５こ０で３
５分間反応させたところ、ピログルタミルグリシルアラ
ニン０．６夕（０．００２モル）が得られた。Example 1 3.23 moles (0.025 moles) of pyroglutamic acid, 0.95 moles (0.013 moles) of glycine, and 3.35 moles (0.038 moles) of alanine were thoroughly ground in a mortar and mixed.
While flowing N2 gas in a glass reaction tube, the temperature was 3 at 175℃.
After reacting for 5 minutes, 0.6 moles (0.002 mol) of pyroglutamylglycylalanine was obtained.
その他、ピログルタミルアラニン１．２夕（０．００６
モル）とピログルタミルグリシン１．０夕（０．００５
モル）が得られ、ピログルタミン酸１．６を回収Ｌた。
ピログルタミン酸の転化率５２％、ピログルタミルグリ
シルァラニンの収率８％、選択率１５．４％であった。In addition, pyroglutamylalanine 1.2 evenings (0.006
mole) and pyroglutamylglycine 1.0 mole (0.005 mole)
mol) was obtained and 1.6 pyroglutamic acid was recovered.
The conversion rate of pyroglutamic acid was 52%, the yield of pyroglutamylglycylalanine was 8%, and the selectivity was 15.4%.
生成物の分離および分折は、水溶液にして、Ｓｈｏｄｅ
ｘ Ｉｏｎ−ＥｘｃｈａｎｇｅｒＨＣ−８一１０カラム
を用いる高速液体クロマトグラフイで行った。比較例
１ピログルタミン酸とグリシンとアラニンを１：１：１
モル比に混合して、上記と全く同様の反応を行ったとこ
ろ、主生成物は、ピログルタミルグリシンとピログルタ
ミルグリシルグリシンであり、他に、ピログルタミルグ
リシルグリシルグリシンや、ピログルタミルアラニルグ
リシンも創生し、目的のピログルタミルグリシルアラニ
ンは収率、選択率ともにきわめて低いものであった。Separation and fractionation of the product can be carried out in aqueous solution using Shode
The analysis was performed by high performance liquid chromatography using a x Ion-Exchanger HC-8-10 column. Comparative example
1 Pyroglutamic acid, glycine and alanine 1:1:1
When they were mixed in the same molar ratio and subjected to the same reaction as above, the main products were pyroglutamylglycine and pyroglutamylglycylglycine, and in addition, pyroglutamylglycylglycylglycine and pyroglutamylalanyl. Glycine was also created, and the yield and selectivity of the target pyroglutamylglycylalanine were extremely low.
実施例 ２ピログルタミン酸１．０３夕（０．００８モ
ル）、グリシン０．６３夕（０．００８モル）、８ーア
ラニン２．２３夕（０．０２５モル）の結晶を精秤採取
して乳鉢中でよくすりつぶして混合し、炭酸ガスで置換
したガラス管封中に熔封して、１６０００で４粉ご間反
応させた。Example 2 Crystals of 1.03 moles (0.008 moles) of pyroglutamic acid, 0.63 moles (0.008 moles) of glycine, and 2.23 moles (0.025 moles) of 8-alanine were collected by precise weighing and placed in a mortar. The mixture was thoroughly ground and mixed, sealed in a glass tube sealed with carbon dioxide gas, and reacted between the four powders at 16,000 yen.
反応終了后、生成物を０．１％Ｈ３Ｐ０４水溶液にとか
して、ＳｈｏｄｅｘＩｏｎｐａｃ Ｃ−８１１カラムを
用いる高速液体クロマトグラフィーで分離し、ピログル
タミルグリシルー８−アラニン０．２６夕（０．００１
モル）を得た。他に、ピログルタミル−８ーアラニン０
．４夕（０．００２モル）、ピログルタミルグリシン０
．３７夕（０．００２モル）を得てピログルタミン酸０
．３８夕を回収した。After the reaction was completed, the product was dissolved in 0.1% H3P04 aqueous solution and separated by high performance liquid chromatography using a ShodexIonpac C-811 column to obtain pyroglutamylglycyl-8-alanine 0.26 (0.001
mole) was obtained. In addition, pyroglutamyl-8-alanine 0
．． 4 (0.002 mol), pyroglutamylglycine 0
．． 0.37 (0.002 mol) of pyroglutamic acid was obtained.
．． 38 evenings were collected.
ピログルタミン酸の転化率６３％でピログルタミルグリ
シルー８−アラニンの収率１３％、選択率２１％であっ
た。比較例 ２
ピログルタミン酸とアラニンと８−アラニンを１：１：
１モル比に混合して、上記と全く同様の条件で反応させ
たところ、ピログルタミルアラニンと、ピログルタミル
ー８ーアラニンのみが得られ、トリベプチドの生成は全
くみとめられなかった。The conversion rate of pyroglutamic acid was 63%, the yield of pyroglutamylglycyl-8-alanine was 13%, and the selectivity was 21%. Comparative Example 2 Pyroglutamic acid, alanine, and 8-alanine at 1:1:
When they were mixed at a molar ratio of 1 and reacted under exactly the same conditions as above, only pyroglutamylalanine and pyroglutamyl-8-alanine were obtained, and no formation of tribeptide was observed.
実施例 ３
ピログルタミン酸２．０６夕（０．０１６モル）、グリ
シン０．６３夕（０．００８モル）、チロシン４．５３
夕（０．０２５モル）の結晶を糟秤採取して混合し、窒
素置換したガラス管中に熔封し１８０００、２０分間反
応させた。Example 3 Pyroglutamic acid 2.06 moles (0.016 moles), glycine 0.63 moles (0.008 moles), tyrosine 4.53 moles
The crystals (0.025 mol) were collected on a weighing scale, mixed, sealed in a glass tube purged with nitrogen, and reacted at 18,000 ml for 20 minutes.
実施例２と同様の方法で分析したことろ、ピログルタミ
ルグリシルチロシン０．７９（０．００２モル）が得ら
れた。他の生成物は、ピログルタミルチロシン０．５８
夕（０．００３モル）、ピログルタミルグリシン０．３
夕（０．００２モル）であった。ピログルタミン酸の転
化率 ４３．８％ピログルタミルグリシル
チロシンの収率 ２５％選択率
２８．６％であった。As a result of analysis in the same manner as in Example 2, 0.79 (0.002 mol) of pyroglutamylglycyltyrosine was obtained. Other products include pyroglutamyl tyrosine 0.58
(0.003 mol), pyroglutamylglycine 0.3
(0.002 mol). Conversion rate of pyroglutamic acid: 43.8% Yield of pyroglutamylglycyltyrosine: 25% selectivity
It was 28.6%.
Claims (1)
と、これと異る他のアミノ酸とを１〜２：１：３〜５の
モル比において、加熱することを特徴とするピログルタ
ミルグリシルアミノ酸の製造法。1. A method for producing pyroglutamyl glycylamino acid, which comprises heating glutamic acid or pyroglutamic acid, glycine, and another amino acid different therefrom at a molar ratio of 1 to 2:1:3 to 5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8288177A JPS6035358B2 (en) | 1977-07-13 | 1977-07-13 | Method for producing pyroglutamylglycylamino acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8288177A JPS6035358B2 (en) | 1977-07-13 | 1977-07-13 | Method for producing pyroglutamylglycylamino acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5419967A JPS5419967A (en) | 1979-02-15 |
| JPS6035358B2 true JPS6035358B2 (en) | 1985-08-14 |
Family
ID=13786607
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8288177A Expired JPS6035358B2 (en) | 1977-07-13 | 1977-07-13 | Method for producing pyroglutamylglycylamino acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6035358B2 (en) |
-
1977
- 1977-07-13 JP JP8288177A patent/JPS6035358B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5419967A (en) | 1979-02-15 |
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