N-tert-butoxycarbonyl-O-2,6-dichlorobenzyl-(R)-tyrosine

• 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: N-tert-butoxycarbonyl-O-2,6-dichlorobenzyl-(R)-tyrosine
• 英文别名: Boc-D-tyr(2,6-CL2-bzl)-OH；(2R)-3-[4-[(2,6-dichlorophenyl)methoxy]phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• 化学式: C₂₁H₂₃Cl₂NO₅
• 分子量: 440.323
• InChiKey: DODHIGHXRDNRPP-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.09
• 重原子数：
  29.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  84.86
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-tert-butoxycarbonyl-O-2,6-dichlorobenzyl-(R)-tyrosine 在 盐酸 、 苯甲醚 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 氯仿 为溶剂， 反应 22.0h， 生成 benzyl ((R)-2-((R)-2-((S)-2-((S)-5-(((benzyloxy)carbonyl)amino)-2-((S)-2-((tert-butoxycarbonyl)amino)-3-methylbutanamido)pentanamido)-4-methylpentanamido)-3-phenylpropanamido)-3-(4-((2,6-dichlorobenzyl)oxy)phenyl)propanoyl)-L-prolinate
  参考文献：
  名称：

  Studies on Peptide Antibiotic “Gratisin”

  摘要：

  根据为抗生素多肽格拉亭拟订的一个主要结构，用液相法合成了分别含有部分序列l-苯丙–l-脯–l-酪、d-苯丙–l-脯–l-酪、l-苯丙–l-脯–d-酪和d-苯丙–l-脯–d-酪的四个多肽。其中环(–l-缬–l-鸟–l-亮–d-苯丙–l-脯–d-酪–)2 对所试的革兰氏阳性微生物表现最强的活性。它对枯草杆菌的活性与短杆菌肽 S的相似。因此，天然格拉亭与这个多肽很可能就是同一个东西。为了便于进一步探讨结构与活性关系，制备了四个别的类似物。从它们的抗生素活性的结果看出，把 d-苯丙残基换成d-酪残基会使活性降低，而 d-酪残基的羟基对此活性没有重要作用。具有部分序列 d-苯丙–d-酪–l-脯和 l-脯–d-苯丙–d-苯丙的各个多肽表现很强的活性。这些情况说明，脯残基的位置并不是非固定在5 及 5'不可才表现出活性。这些合成多肽在溶液中的圆二色性光谱反映了脯残基周围的部分序列，它们对这些合成抗生素的构象有很大影响。这些圆二色性光谱的温度依赖关系指出，有生物活性的多肽的构象比活性较小的多肽的构象更稳定些。

  DOI：

  10.1246/bcsj.57.3210

文献信息

• Diagnostic or therapeutic somatostatin or bombesin analog conjugates and uses thereof
  申请人：Coy H. David

  公开号：US20050070470A1

  公开（公告）日：2005-03-31

  Disclosed are peptide agents and uses thereof that are analogs of biologically active peptides such as somatostatin and bombesin. The compounds of the invention have the general formula X-Y-Z-Q, where X is a cytotoxic agent, therapeutic agent, detectable label or chelating group, and Q is a biologically active peptide. In peptide agents of the invention Y is optionally a hydrophilic polymer or peptide, and Z is a linking peptide bonded to Q at the amino terminus of Q, having two, three, four, or five, amino acid residues selected to link X to Q, while retaining the biological activity of Q. Methods of using these peptide agents in the diagnosis and treatment of diseases are also disclosed.

  披露了肽剂及其用途，它们是生物活性肽的类似物，例如生长抑素和蛙皮素。发明的化合物具有通式X-Y-Z-Q，其中X是细胞毒素、治疗剂、可检测的标签或螯合基团，Q是生物活性肽。在发明的肽剂中，Y是可选的水溶性聚合物或肽，Z是与Q的氨基端连接的连接肽，具有两个、三个、四个或五个氨基酸残基，选择将X连接到Q，同时保留Q的生物活性。还披露了使用这些肽剂在疾病的诊断和治疗中的方法。
• Studies of a Peptide Antibiotic “Gratisin”. II
  作者：Makoto Tamaki、Michiaki Takimoto、Ichiro Muramatsu

  DOI：10.1246/bcsj.60.2101

  日期：1987.6

  In order to investigate the structure-activity relationship of the “gratisin”-related peptide, cyclo(–Val–Orn–Leu–d-Phe–Pro–d-Tyr–)2 (GR-I), its two analogs, cyclo(–Val–Orn–Leu–d-Ala–Pro–d-Tyr–)2 (6a) and cyclo(–Val–Orn–Leu–d-Phe–Pro–d-Ala–)2 (6b), were synthesized. The CD spectra of these synthetic peptides in an aqueous solution were similar to that of GR-I, indicating that these peptides have similar conformations in an aqueous solution. The activity of 6b was half that of GR-I, whereas 6a did not show any antibiotic activity. These results indicated that the phenyl group of the d-Phe residue preceding the Pro residue is essential for exhibiting the activity, while the p-hydroxyphenyl group of the d-Tyr residue following the Pro residue is not essential.

  为了研究 "gratisin "相关多肽环(-Val-Orn-Leu-d-Phe-Pro-d-Tyr-)2（GR-I）的结构-活性关系，合成了其两个类似物环(-Val-Orn-Leu-d-Ala-Pro-d-Tyr-)2 (6a)和环(-Val-Orn-Leu-d-Phe-Pro-d-Ala-)2 (6b)。这些合成肽在水溶液中的 CD 光谱与 GR-I 相似，表明这些肽在水溶液中具有相似的构象。6b 的活性是 GR-I 的一半，而 6a 则没有显示出任何抗生素活性。这些结果表明，Pro残基之前的d-Phe残基的苯基是显示活性的必要条件，而Pro残基之后的d-Tyr残基的对羟基苯基则不是必要条件。
• Efficient syntheses of geodiamolide A and jaspamide, cytotoxic and antifungal cyclic depsipeptides of marine sponge origin
  作者：Takayuki Imaeda、Yasumasa Hamada、Takayuki Shioiri

  DOI：10.1016/s0040-4039(00)75846-1

  日期：——

  Geodiamolide A (1a) and jaspamide (2) have been efficiently synthesized by use of the Evans asymmetric alkylation, the Mitsunobu esterification, and the DPPA macrolactamization as key steps.

  通过使用Evans不对称烷基化，Mitsunobu酯化和DPPA大内酰胺化作为关键步骤，有效地合成了Geodiamolide A（1a）和jaspamide（2）。
• Tuftsin derivatives
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP0454302A2

  公开（公告）日：1991-10-30

  Linear or cyclic tetra peptide derivatives of tuftsin which activate immunocompetent cells, i.e., macrophages and polymorphonuclear leukocyte, provide a host-mediated inhibition of the growth of tumors, provide protective effects for infectious diseases such as viral, bacterial and fungal diseases, and exhibit therapeutic effects on autoimmune diseases such as lupus erythematosus, rheumatoid and the like, and therefore, are useful for production of pharmaceutical preparations for the treatment of these diseases.

  土夫素的线性或环状四肽衍生物可激活免疫功能细胞，即巨噬细胞和多形核白细胞，通过宿主介导抑制肿瘤生长，对病毒、细菌和真菌等传染性疾病具有保护作用，对红斑狼疮、类风湿等自身免疫性疾病具有治疗作用，因此可用于生产治疗这些疾病的药物制剂。
• An Expeditious Synthesis of Geodiamolide A, an 18-Membered Cytotoxic Depsipeptide from Marine Sponges
  作者：Takayuki Shioiri、Takayuki Imaeda、Yasumasa Hamada

  DOI：10.3987/com-97-s41

  日期：——

  Geodiamolide A (1) has been efficiently synthesized from the polypropionate and tripeptide units using the Evans asymmetric alkylation, the Mitsunobu esterification, and the macrolactamization with diphenyl phosphorazidate (DPPA) as key steps. Efficient esterification between the complex polyketide and tripeptide units was also realized under high pressure conditions.