Boc-Tyr-azide | 71591-33-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Boc-Tyr-azide
• 英文别名: Boc-Tyr-N3；tert-butyl N-[(2S)-1-azido-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamate
• CAS: 71591-33-8
• 化学式: C₁₄H₁₈N₄O₄
• 分子量: 306.321
• InChiKey: SYDXABWEEADLGD-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.66
• 重原子数：
  22.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  124.39
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  Boc-Tyr-azide 在 N-甲基吗啉 、 苯甲醚 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 3,6-bis(2-Tyr-aminoethyl)-5-methyl-2(1H)-pyrazinone
  参考文献：
  名称：

  Oral Bioavailability of a New Class of μ-Opioid Receptor Agonists Containing 3,6-Bis[Dmt-NH(CH₂)_n]-2(1H)-pyrazinone with Central-Mediated Analgesia

  摘要：

  The inability of opioid peptides to be transported through epithelial membranes in the gastrointestinal tract and pass the blood-brain barrier limits their effectiveness for oral application in an antinociceptive treatment regime. To overcome this limitation, we enhanced the hydrophobicity while maintaining the aqueous solubility properties in a class of opioidmimetic substances by inclusion of two identical N-termini consisting of Dmt (2',6'-dimethyl-L-tyrosine) coupled to a pyrazinone ring platform by means of alkyl chains to yield the class of 3,6-bis[Dmt-NH-(CH2)(n)],1-2(1H)-pyrazinones. These compounds displayed high mu-opioid receptor affinity (K(i)mu = 0.042-0.115 nM) and selectivity (K(i)delta/K(i)mu = 204-307) and functional p-opioid receptor agonism (guinea-pig ileum, IC50 = 1.3-1.9 nM) with little or undetectable bioactivity toward delta-opioid receptors (mouse vas deferens) and produced analgesia in mice in a naloxone reversible manner when administered centrally (intracerebroventricular, icv) or systemically (subcutaneously and orally). Furthermore, the most potent compound, 3,6-bis(3'-Dmt-aminopropyl)-5-methyl-2(1H)-pyrazinone (7') lacked functional delta-opioid receptor bioactivity and was 50-63-fold and 18-21-fold more active than morphine by icv administration as measured analgesia using tail-flick (spinal involvement) and hot-plate (supraspinal effect) tests, respectively; the compound ranged from 16 to 63% as potent upon systemic injection. These analgesic effects are many times greater than unmodified opioid peptides. The data open new possibilities for the rational design of potential opioid-mimetic drugs that pass through the epithelium of the gastrointestinal tract and the blood-brain barrier to target brain receptors.

  DOI：

  10.1021/jm0304616
• 作为产物：
  描述：

  Boc-L-酪氨酸 在 N-甲基吗啉 、 氯甲酸乙酯 、 sodium azide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.08h， 生成 Boc-Tyr-azide
  参考文献：
  名称：

  Efficient Synthesis of O-Succinimidyl-(tert-Butoxycarbonylamino)methyl Carbamates Derived from α-Amino Acids Accelerated by Ultrasound: Application to the Synthesis of Ureidodipeptides

  摘要：

  The synthesis of O-succinimidyl-(tert-butoxycarbonylamino)methyl carbamates employing isocyanates made through the Curtius rearrangement of Boc-amino acid azides in the presence of N-hydroxysuccinimide under the influence of ultrasound is described.

  DOI：

  10.1080/00397910802026386

文献信息

• Amino acids and peptides. XXVIII. Synthesis of peptide fragments related to eglin c and studies on the relationship between their structure and effects on human leukocyte elastase, cathepsin G and .ALPHA.-chymotrypsin.
  作者：Satoshi TSUBOI、Kazunori NAKABAYASHI、Yoshikazu MATSUMOTO、Naoki TENO、Yuko TSUDA、Yoshio OKADA、Yoko NAGAMATSU、Junichiro YAMAMOTO

  DOI：10.1248/cpb.38.2369

  日期：——

  Various peptide fragments related to eglin c, which consists of 70 amino acid residues, were synthesized by a conventional solution method and their inhibitory effects on leukocyte elastase, cathepsin G and α-chymotrypsin were examined. Among them, H-Arg-Glu-Tyr-Phe-OMe (eglin c 22-25) and H-Ser-Pro-Val-Thr-Leu-Asp-Leu-Arg-Tyr-OMe (eglin c 41-49) inhibited cathepsin G and α-chymotrypsin but not leukocyte elastase, while H-Thr-Asn-Val-Val-OMe (eglin c 60-63) inhibited leukocyte elastase but not cathepsin G or α-chymotrypsin, although eglin c potently inhibited leukocyte elastase, cathepsin G and α-chymotrypsin. These results indicated that the interaction sites of eglin c with leukocyte elastase, cathepsin G and α-chymotrypsin might be different.

  采用常规的溶液法合成了与来自家蚕血淋巴的抗蛋白酶eglin c（由70个氨基酸残基构成）相关的各种肽片段，并检验了它们对白细胞弹性蛋白酶、组织蛋白酶G和α-胰凝乳蛋白酶的抑制效应。其中，H-Arg-Glu-Tyr-Phe-OMe（eglin c 22-25）和H-Ser-Pro-Val-Thr-Leu-Asp-Leu-Arg-Tyr-OMe（eglin c 41-49）能抑制组织蛋白酶G和α-胰凝乳蛋白酶，但不能抑制白细胞弹性蛋白酶，而H-Thr-Asn-Val-Val-OMe（eglin c 60-63）能抑制白细胞弹性蛋白酶，但不能抑制组织蛋白酶G或α-胰凝乳蛋白酶，尽管eglin c对白细胞弹性蛋白酶、组织蛋白酶G和α-胰凝乳蛋白酶都具有强抑制作用。这些结果提示，eglin c与白细胞弹性蛋白酶、组织蛋白酶G和α-胰凝乳蛋白酶的相互作用部位可能各不相同。
• Synthesis of peptide chloromethyl ketones and examination of their inhibitory effects on human spleen fibrinolytic proteinase(SFP) and human leukocyte elastase(LE).
  作者：YUKO TSUDA、YOSHIO OKADA、YOKO NAGAMATSU、UTAKO OKAMOTO

  DOI：10.1248/cpb.35.3576

  日期：——

  Various substrate-derived chloromethyl ketones were synthesized by a conventional method for the purpose of obtaining specific and potent irreversible inhibitors for human spleen fibrinolytic proteinase (SFP) and human leukocyte elastase (LE) in order to compare the properties of SFP with those of LE. It was found that Boc-Ala-Tyr-Leu-Val-CH2Cl among the peptide chloromethyl ketones exhibited the most effective and specific inhibition of SFP and LE. The two enzymes were inhibited by peptide chloromethyl ketones having a Val residue at the C-terminus in a similar manner, demonstrating a similarity between SFP and LE.

  为了比较人脾纤溶酶（SFP）和人白细胞弹力酶（LE）的性质，通过传统方法合成了多种来自底物的氯甲基酮，旨在获得对这两种酶具有特异性和强效的不可逆抑制剂。在各种肽氯甲基酮中，发现Boc-Ala-Tyr-Leu-Val-CH2Cl对SFP和LE表现出最有效和特异的抑制作用。这两种酶都被C-末端具有Val残基的肽氯甲基酮以类似方式抑制，这表明SFP和LE之间存在相似性。
• Studies on .ALPHA.2-plasmin inhibitor fragment T-11. I. Synthesis of the protected hexadecapeptide ester corresponding to positions 11 through 26 of .ALPHA.2-plasmin inhibitor fragment T-11.
  作者：TAKASHI SASAKI、SUMIRO ISODA

  DOI：10.1248/cpb.35.2797

  日期：——

  The protected hexadecapeptide ester corresponding to positions 11 through 26 of human α2-plasmin inhibitor fragment T-11, which consists of 26 amino acids and binds to the plasmin (ogen) lysine-binding site (s), was synthesized by assembling five peptide fragments by the azide method or the dicyclohexylcarbodiimide-N-hydroxybenzotriazole method.

  通过对五个肽片段采用叠氮法或二环己基碳二亚胺-N-羟基苯并三唑法进行组装，合成了与人类α2-纤溶酶抑制剂片段T-11的第11至26位对应的受保护十六肽酯，该片段由26个氨基酸组成，并与纤溶酶（原）赖氨酸结合位点（s）结合。
• Studies on peptides. CXXVI. Synthesis of the protected tetracosapeptide corresponding to positions 30-53 of mouse epidermal growth factor (EGF).
  作者：KENICHI AKAJI、NOBUTAKA FUJII、HARUAKI YAJIMA

  DOI：10.1248/cpb.33.173

  日期：——

  As a starting material for the synthesis of mouse epidermal growth factor, a half of the molecule, the protected tetracosapeptide ester (positions 30-53), was synthesized by successive condensations of eight peptide fragments : (positions 51-53), (49-50), (46-48), (42-45), (39-41), (37-38), (34-36), (30-33).

  作为合成小鼠表皮生长因子起始原料的半个分子，即30-53位点的受保护二十四肽酯，是通过八个肽片段（51-53位点，49-50位点，46-48位点，42-45位点，39-41位点，37-38位点，34-36位点，30-33位点）的连续缩合反应合成的。
• Studies on peptides. CXXVII. Synthesis of a tripentacontapeptide with epidermal growth factor activity.
  作者：KENICHI AKAJI、NOBUTAKA FUJII、HARUAKI YAJIMA、KYOZO HAYASHI、KAZUHIKO MIZUTA、MITSURU AONO、MOTOYUKI MORIGA

  DOI：10.1248/cpb.33.184

  日期：——

  The tripentacontapeptide corresponding to the entire linear sequence of epidermal growth factor was synthesized by assembling 15 peptide fragments and one His residue (position 22), followed by deprotection with trifluoromethanesulfonic acid-thioanisole in trifluoroacetic acid. The deprotected peptide was subjected to air-oxidation. After purification by ion-exchange chromatography on diethyl aminoethyl cellulose followed by high performance liquid chromatography, a peptide with powerful anti-gastric activity was obtained.

  通过组装15个肽片段和一个组氨酸残基（位置22），合成了对应于表皮生长因子整个线性序列的三十五肽。随后，通过三氟甲磺酸-噻吩在三氟乙酸中进行脱保护。脱保护的肽进行空气氧化。经过二乙氨基乙基纤维素上的离子交换色谱法纯化，接着用高效液谱法，获得了一种具有强大抗胃活性的肽。