JPS5912119B2 - Method for producing amino acid derivatives - Google Patents
Method for producing amino acid derivativesInfo
- Publication number
- JPS5912119B2 JPS5912119B2 JP52130103A JP13010377A JPS5912119B2 JP S5912119 B2 JPS5912119 B2 JP S5912119B2 JP 52130103 A JP52130103 A JP 52130103A JP 13010377 A JP13010377 A JP 13010377A JP S5912119 B2 JPS5912119 B2 JP S5912119B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- mol
- acid
- amino acid
- solution
- 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
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 150000003862 amino acid derivatives Chemical class 0.000 title 1
- 150000001413 amino acids Chemical class 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 238000006116 polymerization reaction Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 18
- 229940024606 amino acid Drugs 0.000 description 12
- 235000001014 amino acid Nutrition 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- HDFRDWFLWVCOGP-UHFFFAOYSA-N carbonothioic O,S-acid Chemical compound OC(S)=O HDFRDWFLWVCOGP-UHFFFAOYSA-N 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 3
- -1 alkali metal salt Chemical class 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- 229960002989 glutamic acid Drugs 0.000 description 3
- 229960002885 histidine Drugs 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 2
- QCHPKSFMDHPSNR-UHFFFAOYSA-N 3-aminoisobutyric acid Chemical compound NCC(C)C(O)=O QCHPKSFMDHPSNR-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 229960004799 tryptophan Drugs 0.000 description 2
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- KIWBPDUYBMNFTB-UHFFFAOYSA-N Ethyl hydrogen sulfate Chemical compound CCOS(O)(=O)=O KIWBPDUYBMNFTB-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 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
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-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
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000003524 antilipemic agent Substances 0.000 description 1
- 229940000635 beta-alanine Drugs 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 150000002333 glycines Chemical class 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 235000005772 leucine Nutrition 0.000 description 1
- 239000010446 mirabilite Substances 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
- 235000008729 phenylalanine Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 235000014393 valine Nutrition 0.000 description 1
Description
【発明の詳細な説明】
１５本発明は一般式〔Ｉ〕
Ｈ壬Ｓ−Ｙ−Ｃｏチｎ０ＨＣＩ〕
（式中、Ｙは１〜３個の炭素原子を有する直鎖又２０は
分枝のアルキレン基を示し、該アルキレン基はフェニル
基で置換されていてもよい。Detailed Description of the Invention 15 The present invention relates to the general formula [I] The alkylene group may be substituted with a phenyl group.
ｎは平均分子量が１６６〜１５００となる重合度を示す
。）で表わされるポリチオエステルに一般式〔■〕で表
わされるアミノ酸ＮＨ２−ＣＨ−（ＣＨ２）ｍ−ＣＯＯ
Ｈ〔■〕３０（式中、Ｒは水素原子、低級アルキル基、
フェニル基または置換低級アルキル基を示し、該置換基
はメルカプト基、カルボキシル基、フェニル基、イミダ
ゾリル基またはインドリル基を示す。n indicates the degree of polymerization at which the average molecular weight is from 166 to 1,500. ) to the polythioester represented by the amino acid NH2-CH-(CH2)m-COO represented by the general formula [■]
H [■] 30 (wherein R is a hydrogen atom, a lower alkyl group,
It represents a phenyl group or a substituted lower alkyl group, and the substituent represents a mercapto group, a carboxyl group, a phenyl group, an imidazolyl group or an indolyl group.
ｍは０〜４を示す。）３５を反応させることを特徴とす
る一般式〔■〕（式中、Ｙ，．Ｒ及びｍは上記と同義）
で表わされるＮ−（メルカプトアシル）アミノ酸の製造
方法に関する。m indicates 0-4. ) General formula [■] characterized by reacting 35 (wherein, Y, .R and m have the same meanings as above)
The present invention relates to a method for producing an N-(mercaptoacyl)amino acid represented by
本発明によつて得られる一般式〔〕で示される化合物は
医薬特に喀痰溶解剤、脂質低下剤、降圧剤、重金属の排
泄促進剤として有用である。The compound represented by the general formula [] obtained by the present invention is useful as a medicine, particularly as a sputum solubilizing agent, a lipid lowering agent, an antihypertensive agent, and a heavy metal excretion promoter.
これらのＮ−（メルカブトアシル）アミノ酸の製造法に
ついては種々の方法が提示されている。しかしながら従
来０製造法は必ずしも満足される工業的製造法とはいい
難い。即ち反応経路が長いかまたは液体アンモニア、金
属ナトリウムのような取扱上危険性のある原料薬品を必
要とする等の欠点がある。本発明者は鋭意研究を重ねた
結果、上記Ｎ−（メルカブトアシル）アミノ酸を従来の
方法に比し容易にしかも工業的に有利に製造し得る方法
を見い出し、本発明を完成した。Various methods have been proposed for producing these N-(mercabutoacyl) amino acids. However, the conventional 0 manufacturing method cannot necessarily be said to be a satisfactory industrial manufacturing method. That is, there are drawbacks such as a long reaction route or the need for raw chemicals such as liquid ammonia or metallic sodium that are dangerous to handle. As a result of extensive research, the present inventors have discovered a method for producing the above-mentioned N-(mercabutoacyl)amino acid that is easier and more industrially advantageous than conventional methods, and has completed the present invention.
以下；本発明方法を詳しく説明する。Below, the method of the present invention will be explained in detail.
ポリチオエステルはＭ．ＰｉｅｔｒＯＣＡｔｔＳＯｃ．
ＰｅｌＯｒｉｔａｎａＳｃｉ．Ｆｉ８．Ｍａｔ．Ｎａｔ
ｕｒ．、１１、４５７（１９６５）；Ｃｈｅｍ．Ａｂｓ
ｔｒ．、６７、５４０６８ｅ（１９６７）］の方法に従
いメルカプトカルボン酸の酢酸エチル、テトラヒドロフ
ラン、クロロホルム等の有機溶媒溶液とＮ−Ｎ′−ジシ
クロヘキシルカルボジイミドの有機溶媒溶液とを反応さ
せ生成するＮ−Ｎ′−ジシクロヘキシル尿素を分離しポ
リチオエステルを有機溶媒溶液として得ることができる
。本発明においてはこの溶液をそのままあるいは濃縮し
てアミノ酸との反応に使用すればよい。第１表において
代表的なポリチオエステルの分子量分布を示す。表
Ｍｎ：数平均分子量
Ｍｗ：重量平均分子量
Ｍｚ：Ｚ平均分子量
ポリチオエステルとアミノ酸とを反応さすにはアミノ酸
を適当な溶媒例えば水、メタノール、酢酸エチル等に溶
解させて行えばよく、この場合アミノ酸をアルカリ金属
塩とすることが溶解性のため好ましい。Polythioester is M. PietrOCAttSOc.
PelOritanaSci. Fi8. Mat. Nat
ur. , 11, 457 (1965); Chem. Abs
tr. , 67, 54068e (1967)] by reacting a solution of a mercaptocarboxylic acid in an organic solvent such as ethyl acetate, tetrahydrofuran, or chloroform with a solution of N-N'-dicyclohexylcarbodiimide in an organic solvent. Urea can be separated and polythioester can be obtained as a solution in an organic solvent. In the present invention, this solution may be used as it is or after being concentrated for the reaction with the amino acid. Table 1 shows the molecular weight distribution of typical polythioesters. Table Mn: Number average molecular weight Mw: Weight average molecular weight Mz: Z average molecular weight The reaction between polythioester and amino acid can be carried out by dissolving the amino acid in a suitable solvent such as water, methanol, ethyl acetate, etc. In this case, the amino acid It is preferable to use an alkali metal salt for better solubility.
反応後は濃縮、抽出およびその他の慣用手段により目的
化合物を分離すればよい。本発明にいうアミノ酸として
はグリシン、アラニン、バリン、ロイシン、システイン
、フエニルアラニン ヒスチジン、トリブトフアン、ア
スバラギン酸、グルタミン酸、α−アミノ−ｎ一酪酸、
α−アミノ−イソ酪酸、α−アミノ−ｎ−カプロン酸、
β−アラニン、β−アミノ−ｎ一酪酸、β−アミノ−イ
ソ酪酸、γ−アミノ−ｎ一酪酸、δ−アミノ−ｎ一吉草
酸、６−アミノ−ｎ−ヘキサン酸、等種々のアミノ酸を
あげることができる。次に実施例を挙げて本発明を具体
的に説明する。参考例第２表のＹに示す種々の基を有す
るメルカブトカルボン酸（０．３モル）を酢酸エチル３
００７！１１に溶解し、これに氷冷攪拌下Ｎ−Ｎ′−ジ
シクロヘキシルカルボジイミド（０．３モル）の酢酸エ
チル２５０ｍ１溶液を滴下する。After the reaction, the target compound may be separated by concentration, extraction, or other conventional means. Amino acids referred to in the present invention include glycine, alanine, valine, leucine, cysteine, phenylalanine histidine, tributophane, asbaragic acid, glutamic acid, α-amino-n-monobutyric acid,
α-amino-isobutyric acid, α-amino-n-caproic acid,
Various amino acids such as β-alanine, β-amino-n-monobutyric acid, β-amino-isobutyric acid, γ-amino-n-monobutyric acid, δ-amino-n-monovaleric acid, 6-amino-n-hexanoic acid, etc. I can give it to you. Next, the present invention will be specifically explained with reference to Examples. Reference Example Mercabutocarboxylic acid (0.3 mol) having various groups shown in Y in Table 2 was mixed with ethyl acetate 3
007!11, and a solution of N-N'-dicyclohexylcarbodiimide (0.3 mol) in 250 ml of ethyl acetate was added dropwise thereto under ice-cooling and stirring.
滴下後室温で更に１時間攪拌した後、析出したＮ−Ｎ″
−ジシクロヘキシル尿素を濾去し、濾液を減圧濃縮し約
２００ｍ１としポリチオエステルの酢酸エチル溶液を得
る。実施例 １システイン（０．３モル）および炭酸カ
リウム（０．１６モル）を水１７０７７！／に溶解し、
メタノール１７０Ｔ！Ｌｔを加える。After the dropwise addition, the precipitated N-N'' was stirred at room temperature for an additional hour.
-Dicyclohexylurea is removed by filtration, and the filtrate is concentrated under reduced pressure to a volume of about 200 ml to obtain a solution of polythioester in ethyl acetate. Example 1 Cysteine (0.3 mol) and potassium carbonate (0.16 mol) were added to 17077 ml of water! / dissolved in
Methanol 170T! Add Lt.
これに参考例で得たポリチオエステルの酢酸エチル溶液
を加え室温で４時間攪拌し、一夜放置する。反応液を減
圧濃縮して得られる水溶液は酸性とし酢酸エチルにて抽
出する。To this was added an ethyl acetate solution of the polythioester obtained in Reference Example, stirred at room temperature for 4 hours, and left overnight. The aqueous solution obtained by concentrating the reaction solution under reduced pressure is made acidic and extracted with ethyl acetate.
抽出液は水洗、芒硝乾燥後溶媒を留去して下記第２表に
示すＮ−（メルカプトアシル）システインを得る。実施
例 ２
Ｌ−ヒスチジン（０．３モル）および炭酸カリウム（０
，１６モル）を水２００ｄに溶解し、メタノール２００
１１１を加える。The extract was washed with water, dried over Glauber's salt, and the solvent was distilled off to obtain N-(mercaptoacyl)cysteine shown in Table 2 below. Example 2 L-histidine (0.3 mol) and potassium carbonate (0
, 16 mol) in 200 d of water, and 200 d of methanol.
Add 111.
この溶液に、第３表のＹに示す基を有するメルカプトカ
ルボン酸（０．３モル）を参考例と同様処理して得たポ
リチオエステルの酢酸エチル溶液を加え室温で４時間攪
拌し、一夜放置する。反応液を減圧濃縮して得られる水
溶液は酢酸エチルで洗滌した後塩酸酸性（ＰＨｌ）とす
る。To this solution, an ethyl acetate solution of polythioester obtained by treating mercaptocarboxylic acid (0.3 mol) having the group shown in Y in Table 3 in the same manner as in the reference example was added, stirred at room temperature for 4 hours, and left overnight. do. The aqueous solution obtained by concentrating the reaction solution under reduced pressure is washed with ethyl acetate and then acidified with hydrochloric acid (PHI).
再び酢酸エチルで洗滌し塩酸を加えＰＨ３乃至ＰＨ４と
しエタノール１００１１ＬＩを加えると結晶が析出する
。結晶は濾取、乾燥して下記第３表に示すＮ一（メルカ
プトアシル）−Ｌ−ヒスチジンを得る。実施例 ３
第４表のＹに示す種々の基を有するメルカプトカルボン
酸（０．１モル）の酢酸エチル１００ｄ溶液、Ｎ−Ｎ５
−ジシクロヘキシルカルボジイミド（０．１モル）の酢
酸エチル７０耐溶液、グリシン（またはフエニルグリシ
ン（０．１モル）、炭酸カリウム（０．０５モル）、水
５０ｄおよびメタノール５０ｄを用い参考例及び実施例
１と同様に処理することにより、下記第４表に示すＮ−
（メルカプトアシル）一置換グリシンを得る。Wash again with ethyl acetate, add hydrochloric acid to adjust the pH to 3 or 4, and add ethanol 10011LI to precipitate crystals. The crystals were collected by filtration and dried to obtain N-(mercaptoacyl)-L-histidine shown in Table 3 below. Example 3 A 100 d solution of mercaptocarboxylic acids (0.1 mol) in ethyl acetate having various groups indicated by Y in Table 4, N-N5
-Reference Examples and Examples using a 70-proof solution of dicyclohexylcarbodiimide (0.1 mol) in ethyl acetate, glycine (or phenylglycine (0.1 mol), potassium carbonate (0.05 mol), 50 d of water, and 50 d of methanol) By processing in the same manner as in 1, N- shown in Table 4 below is obtained.
(Mercaptoacyl) monosubstituted glycine is obtained.
実施例 ４
２−メルカブトプロピオン酸（０．１モル）の酢酸エチ
ル１００１１１溶液、Ｎ−Ｎ′−ジシクロヘキシルカル
ボジイミド（０．１モル）ｑ詐酸エチル７０ｒ！Ｌｔ溶
液、第５に示す種々のアミノ酸（０．１モル）、炭酸カ
リウム（０．０５モル）、水５０ｍ１およびメタノール
５０ｄを用い参考例及び実施例１と同様に処理して、下
記第５表に示すＮ−（メルカプトアシル）一置換アミノ
酸を得る。Example 4 100111 solution of 2-merkabutopropionic acid (0.1 mol) in ethyl acetate, N-N'-dicyclohexylcarbodiimide (0.1 mol) q ethyl sulfate 70r! The Lt solution, various amino acids shown in No. 5 (0.1 mol), potassium carbonate (0.05 mol), 50 ml of water, and 50 d of methanol were treated in the same manner as in Reference Example and Example 1 to obtain the results shown in Table 5 below. The N-(mercaptoacyl) monosubstituted amino acid shown is obtained.
実施例 ５
第６表のＹに示す種々の基を有するメルカプトカルボン
酸（０，２モル）の酢酸エチル２００ｍ１溶液、Ｎ−Ｎ
５−ジシクロヘキシルカルボジイミド（０．２モル）の
酢酸エチル１６０ｍ１溶液、Ｌ−トリプトフアン（０．
２モル）、炭酸カリウム（０．１１モル）、水２００ｍ
１およびメタノール２００ｍ２を用い参考例及び実施例
２と同様に処理して、下記第６表に示すＮ−（メルカプ
トアシル）−Ｌ−トリプトフアンを得る。Example 5 A solution of mercaptocarboxylic acids (0.2 mol) having various groups indicated by Y in Table 6 in 200 ml of ethyl acetate, N-N
A solution of 5-dicyclohexylcarbodiimide (0.2 mol) in 160 ml of ethyl acetate, L-tryptophan (0.2 mol),
2 mol), potassium carbonate (0.11 mol), water 200m
1 and 200 m2 of methanol in the same manner as in Reference Example and Example 2 to obtain N-(mercaptoacyl)-L-tryptophan shown in Table 6 below.
実施例 ６
第７表のＹに示す基を有するメルカプトカルボン酸（０
．１モル）の酢酸エチル２００ｍ１溶液、Ｎ・Ｎ５−ジ
シクロヘキシルカルボジイミド（０．１モル）の酢酸エ
チル１６０ｍ１溶液、Ｌ−グルタミン酸０．１モル、炭
酸カリウム（０．１モル）、水１１０ｍ１およびメタノ
ール１１０ｍ１を用い参渚例及び実施例１と同様に処理
して、下記第７表に示すＮ一（メルカプトアシル）−Ｌ
−グルタミン酸を得る。Example 6 Mercaptocarboxylic acid (0
．． 1 mol) of ethyl acetate, 160 ml of a solution of N.N5-dicyclohexylcarbodiimide (0.1 mol) in ethyl acetate, 0.1 mol of L-glutamic acid, potassium carbonate (0.1 mol), 110 ml of water, and 110 ml of methanol. The N1 (mercaptoacyl)-L shown in Table 7 below was treated in the same manner as the beach example and Example 1.
- Obtain glutamic acid.
Claims (1)
のアルキレン基を示し、該アルキレン基はフェニル基で
置換されていてもよい。 ｎは平均分子量が１６６〜１５００となる重合度を示す
。）で表わされるポリチオエステルに一般式〔II〕で表
わされるアミノ酸▲数式、化学式、表等があります▼〔
II〕（式中、Ｒは水素原子、低級アルキル基、フェニル
基または置換低級アルキル基を示し、該置換基はメルカ
プト基、カルボキシル基、フェニル基、イミダゾリル基
またはインドリル基を示す。 ｍは０〜４を示す。）を反応させることを特徴とする一
般式〔III〕▲数式、化学式、表等があります▼〔III〕
（式中、Ｙ、Ｒ及びｍは上記と同義） で表わされるＮ−（メルカプトアシル）アミノ酸の製造
方法。[Claims] 1 General formula [I] H■S-Y-CO■_nOH [I] (wherein, Y represents a linear or branched alkylene group having 1 to 3 carbon atoms, The alkylene group may be substituted with a phenyl group. n indicates the degree of polymerization such that the average molecular weight is 166 to 1500. There are tables etc.▼〔
II] (wherein R represents a hydrogen atom, a lower alkyl group, a phenyl group, or a substituted lower alkyl group, and the substituent represents a mercapto group, a carboxyl group, a phenyl group, an imidazolyl group, or an indolyl group. m is 0 to 4) is reacted [III] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [III]
(wherein Y, R and m have the same meanings as above) A method for producing an N-(mercaptoacyl)amino acid represented by:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP52130103A JPS5912119B2 (en) | 1977-10-29 | 1977-10-29 | Method for producing amino acid derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP52130103A JPS5912119B2 (en) | 1977-10-29 | 1977-10-29 | Method for producing amino acid derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5463017A JPS5463017A (en) | 1979-05-21 |
| JPS5912119B2 true JPS5912119B2 (en) | 1984-03-21 |
Family
ID=15026009
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP52130103A Expired JPS5912119B2 (en) | 1977-10-29 | 1977-10-29 | Method for producing amino acid derivatives |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5912119B2 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4256761A (en) * | 1979-07-13 | 1981-03-17 | Usv Pharmaceutical Corporation | Antihypertensive amides |
| JPS5732260A (en) * | 1980-08-07 | 1982-02-20 | Meito Sangyo Kk | Mercaptofatty acid derivative and its preparation |
| US5670545A (en) * | 1996-02-09 | 1997-09-23 | Board Of Regents Of The University Of Colorado | Method for the treatment of ischemic disease and reperfusion injury and the prevention of the adverse effects of reactive oxygen species |
| WO2022153101A1 (en) | 2021-01-12 | 2022-07-21 | Optimus Drugs Private Limited | Crystalline form i of bucillamine |
-
1977
- 1977-10-29 JP JP52130103A patent/JPS5912119B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5463017A (en) | 1979-05-21 |
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