JPS6332800B2 - - Google Patents
Info
- Publication number
- JPS6332800B2 JPS6332800B2 JP55069560A JP6956080A JPS6332800B2 JP S6332800 B2 JPS6332800 B2 JP S6332800B2 JP 55069560 A JP55069560 A JP 55069560A JP 6956080 A JP6956080 A JP 6956080A JP S6332800 B2 JPS6332800 B2 JP S6332800B2
- Authority
- JP
- Japan
- Prior art keywords
- amino
- leucyl
- valyl
- hydroxy
- methyl
- 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
- -1 leucine ester Chemical class 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 4
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
- 239000000126 substance Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- ILJHWMOPCBSXLW-SILRIGIJSA-N (2S)-2-[(4-amino-3-hydroxy-6-methylheptanoyl)-[(2S)-3-methyl-2-[[(2S)-4-methyl-2-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]pentanoyl]amino]butanoyl]amino]propanoic acid Chemical compound C(C1=CC=CC=C1)OC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N([C@@H](C)C(=O)O)C(CC(C(CC(C)C)N)O)=O ILJHWMOPCBSXLW-SILRIGIJSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 230000001766 physiological effect Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 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 2
- DFVFTMTWCUHJBL-UHFFFAOYSA-N 4-azaniumyl-3-hydroxy-6-methylheptanoate Chemical compound CC(C)CC(N)C(O)CC(O)=O DFVFTMTWCUHJBL-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000002467 anti-pepsin effect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 239000003456 ion exchange resin Substances 0.000 description 2
- 229920003303 ion-exchange polymer Polymers 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000013076 target substance Substances 0.000 description 2
- UALXQWNUXKECJD-SFHVURJKSA-N (4-nitrophenyl) (2s)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoate Chemical compound N([C@@H](CC(C)C)C(=O)OC=1C=CC(=CC=1)[N+]([O-])=O)C(=O)OCC1=CC=CC=C1 UALXQWNUXKECJD-SFHVURJKSA-N 0.000 description 1
- WFIYPADYPQQLNN-UHFFFAOYSA-N 2-[2-(4-bromopyrazol-1-yl)ethyl]isoindole-1,3-dione Chemical compound C1=C(Br)C=NN1CCN1C(=O)C2=CC=CC=C2C1=O WFIYPADYPQQLNN-UHFFFAOYSA-N 0.000 description 1
- 108091005508 Acid proteases Proteins 0.000 description 1
- 206010061459 Gastrointestinal ulcer Diseases 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
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 108010036222 Pepstatins Proteins 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000004665 fatty acids Chemical group 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229950003188 isovaleryl diethylamide Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000004474 valine Substances 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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Description
【発明の詳細な説明】
本発明は次式（）
を有する新規ベンジルオキシカルボニル−ロイシ
ル−ロイシル−バリル−４−アミノ−３−ヒドロ
キシ−６−メチル−ヘプタノイル−アラニンおよ
びその製造法に関する。[Detailed Description of the Invention] The present invention is based on the following formula () The present invention relates to a novel benzyloxycarbonyl-leucyl-leucyl-valyl-4-amino-3-hydroxy-6-methyl-heptanoyl-alanine and a method for producing the same.
従来、ストレプトマイセス属微生物の産生する
生理活性物質としてペプシジン類（特許第818156
号、および特開昭49−125583号参照）およびペプ
スタチン類（特公昭47−8996号、特開昭47−
29582号および特開昭49−41590号参照）が知られ
ている。それらは同一の基本構造を有するＮ−ア
シル−ペンタペプタイド、即ちＮ−アシル−バリ
ル−バリル−４−アミノ−３−ヒドロキシ−６−
メチル−ヘプタノイル−アラニル−４−アミノ−
３−ヒドロキシ−６−メチル−ヘプタン酸であ
り、アシル部分として種々の脂肪酸残基を結合し
ている。このＮ−アシルペンタペプタイド類は一
般に抗ペプシン作用および酸性プロテアーゼ阻害
作用たとえば抗レニン作用を有することが知られ
ており、〔ザ・ジヤーナル・オブ・アンチバイオ
テイツクス（J.Antibiotics、26、539〜541
（1973）〕医薬品としての利用が期待される物質で
ある。 Conventionally, pepcidins (Patent No. 818156) have been used as physiologically active substances produced by Streptomyces microorganisms.
(see Japanese Patent Publication No. 49-125583) and pepstatins (Japanese Patent Publication No. 47-8996, Japanese Patent Application Laid-open No. 1987-125583)
29582 and Japanese Unexamined Patent Publication No. 49-41590) are known. They are N-acyl-pentapeptides with the same basic structure, namely N-acyl-valyl-valyl-4-amino-3-hydroxy-6-
Methyl-heptanoyl-alanyl-4-amino-
3-Hydroxy-6-methyl-heptanoic acid, with various fatty acid residues attached as acyl moieties. These N-acyl pentapeptides are generally known to have anti-pepsin effects and acid protease inhibitory effects, such as anti-renin effects [J. Antibiotics, 26 , 539- 541
(1973)] It is a substance that is expected to be used as a medicine.
しかしながら、１つの物質が複数の生理活性を
有することは、当該物質を医療に応用する場合必
ずしも有利とはいえない。即ち、ある物質の１つ
の生理活性をある疾病の治療に応用する場合、他
の生理活性は不必要であるかまたは好ましくない
副作用となるからである。 However, it is not necessarily advantageous for one substance to have multiple physiological activities when applying the substance to medical treatment. That is, when one physiological activity of a certain substance is applied to the treatment of a certain disease, other physiological activities are unnecessary or cause undesirable side effects.
本発明の新規ベンジルオキシカルボニル−ロイ
シル−ロイシル−バリル−４−アミノ−３−ヒド
ロキシ−６−メチル−ヘプタノイル−アラニン
は、上記Ｎ−アシルペンタペプタイドの基本構
造、即ちバリル−４−アミノ−３−ヒドロキシ−
６−メチル−ヘプタノイル−アラニンのＮ端にベ
ンジルオキシカルボニル−ロイシル−ロイシル基
を結合した物質である。上述のＮ−アシルペンタ
ペプタイド類と異なり、本発明の目的物（）は
強力な抗ペプシン活性を有するけれども、抗レニ
ン活性を有していないという特徴をもつており、
ペプシンの分泌亢進に基く諸疾患たとえば消化管
潰瘍の予防治療への応用が期待される物質であ
る。 The novel benzyloxycarbonyl-leucyl-leucyl-valyl-4-amino-3-hydroxy-6-methyl-heptanoyl-alanine of the present invention has the basic structure of the above N-acyl pentapeptide, namely valyl-4-amino-3- hydroxy-
It is a substance in which a benzyloxycarbonyl-leucyl-leucyl group is bonded to the N-terminus of 6-methyl-heptanoyl-alanine. Unlike the above-mentioned N-acyl pentapeptides, the object of the present invention () has a strong anti-pepsin activity but no anti-renin activity.
It is a substance that is expected to be applied to the prevention and treatment of various diseases based on increased secretion of pepsin, such as gastrointestinal ulcers.
本発明の目的物質（）は、次式（）
を有するバリル−４−アミノ−３−ヒドロキシ−
６−メチル−ヘプタノイル−アラニンをＮ−保護
ロイシンエステルと反応させ、Ｎ−保護基を除去
し、得られたロイシル−バリル−４−アミノ−３
−ヒドロキシ−６−メチル−ヘプタノイル−アラ
ニンにベンジルオキシカルボニルロイシンエステ
ルを反応させることによつて製造しうる。Ｎ−保
護基および活性エステルの種類あるいは反応条件
は、ペプタイド合成の技術分野において知られて
いるものから適宜選択して使用することができ
る。 The target substance () of the present invention is expressed by the following formula () valyl-4-amino-3-hydroxy-
6-Methyl-heptanoyl-alanine is reacted with an N-protected leucine ester and the N-protecting group is removed, resulting in leucyl-valyl-4-amino-3
It can be produced by reacting -hydroxy-6-methyl-heptanoyl-alanine with benzyloxycarbonylleucine ester. The types of N-protecting groups and active esters and reaction conditions can be appropriately selected from those known in the technical field of peptide synthesis.
本発明の出発物質（）はまた新規物質である
が、デスアシルバリルペプシジン（特開昭51−
67791号）をたとえば強酸性イオン交換樹脂処理
することによつて得ることができる。 The starting material () of the present invention is also a new substance, desacylvalylpepcidin (Japanese Patent Application Laid-open No.
No. 67791), for example, by treating it with a strongly acidic ion exchange resin.
以下の実施例で本発明をさらに説明する。 The invention is further illustrated in the following examples.
実施例 １
(1) 出発物質バリル−４−アミノ−３−ヒドロキ
シ−６−メチル−ヘプタノイル−アラニン
（）の製造
デスアシルバリルペプシジン17.75ｇを蒸留
水200mlに溶解し、強酸性イオン交換樹脂アン
バーライト（Amberlite）CG120（80ml）を充
填したカラムに負荷した。デスアシルバリルペ
プシジンは全量がカラムに吸着された。カラム
をそのままの状態で30日間放置した。その後、
カラムを水洗し、ついで0.1N水酸化ナトリウ
ム水溶液３で溶出した。ペプタイド含有画分
約1.4を合せ、1N塩酸でPHを５に調整した
後、濃縮乾固して残渣17.8ｇを得た。この残渣
をｎ−ブタノール120mlに溶解し、不溶物を
去した後、液を濃縮して、残渣11.75ｇを得
た。この残渣を蒸留水20mlに溶解し、セフアデ
ツクス（Sephadex）Ｇ−10を担体とするカラ
ムクロマトグラフイで精製した。主画分を合
せ、濃縮乾固し、得られた残渣をエタノールか
ら再結晶して、バリル−４−アミノ−３−ヒド
ロキシ−６−メチル−ヘプタノイル−アラニン
4.3ｇ（収率34.8％）を得た。Example 1 (1) Production of starting material valyl-4-amino-3-hydroxy-6-methyl-heptanoyl-alanine () 17.75 g of desacyl valyl pepcidin was dissolved in 200 ml of distilled water, and strongly acidic ion exchange resin Amber was dissolved in 200 ml of distilled water. It was loaded onto a column packed with Amberlite CG120 (80ml). The entire amount of desacylvalylpepcidin was adsorbed on the column. The column was left as is for 30 days. after that,
The column was washed with water and then eluted with 0.1N aqueous sodium hydroxide solution 3. Approximately 1.4 peptide-containing fractions were combined, the pH was adjusted to 5 with 1N hydrochloric acid, and the mixture was concentrated to dryness to obtain 17.8 g of a residue. This residue was dissolved in 120 ml of n-butanol to remove insoluble matter, and the liquid was concentrated to obtain 11.75 g of a residue. This residue was dissolved in 20 ml of distilled water and purified by column chromatography using Sephadex G-10 as a carrier. The main fractions were combined and concentrated to dryness, and the resulting residue was recrystallized from ethanol to obtain valyl-4-amino-3-hydroxy-6-methyl-heptanoyl-alanine.
4.3g (yield 34.8%) was obtained.
mp：146〜147℃
元素分析：C16H31N3O5・1/2H2Oとして
Ｃ％ Ｈ％ Ｎ％
計算値 54.22 9.10 11.86
測定値 54.80 9.24 11.90
TLC：Rf＝0.37〔キーゼルゲル60G254プレー
ト；展開溶媒：ｎ−ブタノール・酢酸・水
（３：１：１容量比）〕
アミノ酸分析：標品10mgを6N塩酸２mlに溶解
し、110℃で72時間加水分解した。キーゼル
ゲル60G254プレートおよびｎ−ブタノール・
酢酸・水（３：１：１容量比）溶媒を用いる
TLCで加水分解物中のアミノ酸はほぼ等モ
ルずつのバリン、４−アミノ−３−ヒドロキ
シ−６−メチルヘプタン酸およびアラニンか
らなることが認められた。mp: 146-147℃ Elemental analysis: C 16 H 31 N 3 O 5・1/2H 2 O C% H% N% Calculated value 54.22 9.10 11.86 Measured value 54.80 9.24 11.90 TLC: Rf=0.37 [Kieselgel 60G 254 plate ;Developing solvent: n-butanol/acetic acid/water (3:1:1 volume ratio)] Amino acid analysis: 10 mg of the sample was dissolved in 2 ml of 6N hydrochloric acid and hydrolyzed at 110°C for 72 hours. Kieselgel 60G 254 plate and n-butanol
Using acetic acid/water (3:1:1 volume ratio) solvent
TLC revealed that the amino acids in the hydrolyzate consisted of approximately equal moles of valine, 4-amino-3-hydroxy-6-methylheptanoic acid, and alanine.
(2) 目的物質ベンジルオキシカルボニル−ロイシ
ル−ロイシル−バリル−４−アミノ−３−ヒド
ロキシ−６−メチル−ヘプタノイル−アラニン
（）の製造
上記(1)で得られたバリル−４−アミノ−３−
ヒドロキシ−６−メチル−ヘプタノイル−アラ
ニン1.0ｇをジメチルホルムアミド20mlに懸濁
し、ベンジルオキシカルボニルロイシンｐ−ニ
トロフエニルエステル1.2倍モル量を添加し、
室温で96時間撹拌した。反応終了後、反応混合
物を濃縮乾固し、残渣をエーテル洗浄した後、
メタノール160mlに溶解し、10％パラジウム・
炭酸カルシウム400mgを加えて、常法により接
触還元を行なつた。反応液を過し、液を濃
縮乾固し、残渣を熱エタノールに溶解した後冷
却し、析出した沈澱を取して、ロイシル−バ
リル−４−アミノ−３−ヒドロキシ−６−メチ
ル−ヘプタノイル−アラニンの白色粉末877mg
を得た。(2) Production of target substance benzyloxycarbonyl-leucyl-leucyl-valyl-4-amino-3-hydroxy-6-methyl-heptanoyl-alanine () Valyl-4-amino-3-obtained in (1) above
1.0 g of hydroxy-6-methyl-heptanoyl-alanine was suspended in 20 ml of dimethylformamide, and 1.2 times the molar amount of benzyloxycarbonylleucine p-nitrophenyl ester was added.
Stirred at room temperature for 96 hours. After the reaction was completed, the reaction mixture was concentrated to dryness, and the residue was washed with ether.
10% palladium dissolved in 160 ml of methanol.
400 mg of calcium carbonate was added and catalytic reduction was carried out in a conventional manner. The reaction solution was filtered, the solution was concentrated to dryness, the residue was dissolved in hot ethanol and cooled, the precipitate was collected and leucyl-valyl-4-amino-3-hydroxy-6-methyl-heptanoyl- Alanine white powder 877mg
I got it.
上記で得られた白色粉末827mgをジメチルホ
ルムアミド40mlに懸濁し、ベンジルオキシカル
ボニル−ロイシンｐ−ニトロフエニルエステル
1.2倍モル量を添加し、30℃で48時間撹拌した。
反応液を濃縮乾固し、残渣をエチルエーテルで
洗浄して、ベンジルオキシカルボニル−ロイシ
ル−ロイシル−バリル−４−アミノ−３−ヒド
ロキシ−６−メチル−ヘプタノイル−アラニン
1.2ｇ（収率62.5％）を得た。 827 mg of the white powder obtained above was suspended in 40 ml of dimethylformamide, and the benzyloxycarbonyl-leucine p-nitrophenyl ester was suspended in 40 ml of dimethylformamide.
A 1.2-fold molar amount was added, and the mixture was stirred at 30°C for 48 hours.
The reaction solution was concentrated to dryness, and the residue was washed with ethyl ether to give benzyloxycarbonyl-leucyl-leucyl-valyl-4-amino-3-hydroxy-6-methyl-heptanoyl-alanine.
1.2 g (yield 62.5%) was obtained.
mp：207〜208℃（分解）
元素分析：C36H59N5O9・1/2H2Oとして
Ｃ％ Ｈ％ Ｎ％
計算値 60.48 8.46 9.79
実測値 60.80 8.54 10.02
TLC：Rf＝0.76〔キーゼルゲル60G254プレー
ト；展開溶媒：ｎ−ブタノール・酢酸・水
（３：１：１容量比）〕mp: 207-208℃ (decomposition) Elemental analysis: C 36 H 59 N 5 O 9・1/2H 2 O C% H% N% Calculated value 60.48 8.46 9.79 Actual value 60.80 8.54 10.02 TLC: Rf=0.76 [Kieselgel 60G 254 plate; developing solvent: n-butanol/acetic acid/water (3:1:1 volume ratio)]
Claims (1)
ロイシル−バリル−４−アミノ−３−ヒドロキシ
−６−メチル−ヘプタノイル−アラニン。 ２ 次式（） を有するバリル−４−アミノ−３−ヒドロキシ−
６−メチル−ヘプタノイル−アラニンをＮ−保護
ロイシンエステルと反応させ、Ｎ−保護基を除去
し、得られたロイシル−バリル−４−アミノ−３
−ヒドロキシ−６−メチル−ヘプタノイル−アラ
ニンにベンジルオキシカルボニルロイシンエステ
ルを反応させることからなる、式（） を有するベンジルオキシカルボニル−ロイシル−
ロイシル−バリル−４−アミノ−３−ヒドロキシ
−６−メチル−ヘプタノイル−アラニンの製造
法。[Claims] Linear formula () benzyloxycarbonyl-leucyl- with
Leucyl-valyl-4-amino-3-hydroxy-6-methyl-heptanoyl-alanine. Quadratic formula () valyl-4-amino-3-hydroxy-
6-Methyl-heptanoyl-alanine is reacted with N-protected leucine ester and the N-protecting group is removed, resulting in leucyl-valyl-4-amino-3
Formula () consisting of reacting -hydroxy-6-methyl-heptanoyl-alanine with benzyloxycarbonylleucine ester benzyloxycarbonyl-leucyl- with
A method for producing leucyl-valyl-4-amino-3-hydroxy-6-methyl-heptanoyl-alanine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6956080A JPS56166158A (en) | 1980-05-27 | 1980-05-27 | Novel benzyloxycarbonyl-leucyl-leucyl-valyl-4-amino-3- hydroxy-6-methyl-heptanoyl-alanine and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6956080A JPS56166158A (en) | 1980-05-27 | 1980-05-27 | Novel benzyloxycarbonyl-leucyl-leucyl-valyl-4-amino-3- hydroxy-6-methyl-heptanoyl-alanine and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS56166158A JPS56166158A (en) | 1981-12-21 |
| JPS6332800B2 true JPS6332800B2 (en) | 1988-07-01 |
Family
ID=13406252
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6956080A Granted JPS56166158A (en) | 1980-05-27 | 1980-05-27 | Novel benzyloxycarbonyl-leucyl-leucyl-valyl-4-amino-3- hydroxy-6-methyl-heptanoyl-alanine and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS56166158A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4848063B2 (en) * | 2005-09-01 | 2011-12-28 | 株式会社コーワ | Wheel brush |
-
1980
- 1980-05-27 JP JP6956080A patent/JPS56166158A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS56166158A (en) | 1981-12-21 |
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