Cbz-4-碘-L-苯基丙氨酸 | 220400-04-4

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 苯丙氨酸类衍生物
• 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
• 中文名称: Cbz-4-碘-L-苯基丙氨酸
• 中文别名: Cbz-L-4-碘苯丙氨酸
• 英文名称: N-<(Benzyloxy)carbonyl>-4-iodo-L-phenylalanine
• 英文别名: N-benzyloxycarbonyl-4-iodo-L-phenylalanine；N-carboxybenzyl-4-iodo-phenylalanine；Cbz-4-iodo-L-Phe-OH；2S-2-benzyloxycarbonylamino-2-(4-iodo-phenylmethyl)-acetic acid；(S)-2-(((Benzyloxy)carbonyl)amino)-3-(4-iodophenyl)propanoic acid；(2S)-3-(4-iodophenyl)-2-(phenylmethoxycarbonylamino)propanoic acid
• CAS: 220400-04-4
• 化学式: C₁₇H₁₆INO₄
• 分子量: 425.223
• InChiKey: RLQFURMICGBHLW-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2924299090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  Cbz-4-碘-L-苯基丙氨酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride sodium hydroxide 、 sodium periodate 、 ammonium acetate 、 对甲苯磺酸 、 三乙胺 作用下， 以 1,4-二氧六环 、 水 、 丙酮 、 甲苯 为溶剂， 反应 79.0h， 生成 N-benzyloxycarbonyl-4-borono-L-phenylalanine
  参考文献：
  名称：

  A Practical Method for the Synthesis of Enantiomerically Pure 4-Borono-L-phenylalanine

  摘要：

  利用钯催化的频哪醇硼烷（2,3-二甲基-2,3-丁二醇硼）交叉偶联反应，从 L-酪氨酸或 4-碘-L-苯丙氨酸衍生物合成了对映体纯度极高的 L-BPA（4-硼-L-苯丙氨酸）。在[PdCl2(PPh3)2]催化剂存在下，Cbz-Tyr(Nf)-OBzl (2b) 与频哪醇硼烷 (1) 发生交叉偶联反应，得到 N-苄氧羰基-4-(2,3-二甲基-2,3-丁二醇基)-L-苯丙氨酸苄酯 (3a)，收率为 58%。4-碘-L-苯丙氨酸衍生物的反应，如 N-苄氧羰基-4-碘-L-苯丙氨酸苄酯 (2c)、N,N-二苄基-4-碘-L-苯丙氨酸苄酯 (2d)、(4S)-3-苄氧羰基-4-(4-碘苄基)-5-恶唑烷酮(2e)和(4S)-3-叔丁氧羰基-4-(4-碘苄基)-5-恶唑烷酮(2f)，其中 1 在[PdCl2(dppf)]催化剂存在下进行得非常顺利、得到 N-苄氧羰基-4-(2,3-二甲基-2,3-丁二醇二硼酸基)-L-苯丙氨酸苄酯 (3a)、N,N-二苄基-4-(2,3-二甲基-2,3-丁二醇二硼酸基)-L-苯丙氨酸苄酯 (3b)、(4S)-3-苄氧羰基-4-[4-(2、3-(2,3-二甲基-2,3-丁二醇基)苄基]-5-恶唑烷酮 (3c) 和 (4S)-3-丁酰氧羰基-4-[4-(2,3-二甲基-2,3-丁二醇基)苄基]-5-恶唑烷酮 (3d)。对 3a-d 进行脱保护处理后，可得到对映体纯度很高的 L-BPA，总产率也很高。

  DOI：

  10.1246/bcsj.73.231
• 作为产物：
  描述：

  L-苯丙氨酸 在 sodium hydroxide 、 sodium iodate 、 硫酸 、 碘 作用下， 以 溶剂黄146 为溶剂， 反应 22.0h， 生成 Cbz-4-碘-L-苯基丙氨酸
  参考文献：
  名称：

  Efficient Synthesis of a Phosphinate Bis-Amino Acid and Its Use in the Construction of Amphiphilic Peptides

  摘要：

  A new amphiphilic bis-amino acid has been designed and its convergent, asymmetric synthesis achieved in differentially protected form. A convenient preparation of iodophenylalanine, a generally useful starting material, is disclosed. Sequential palladium-catalyzed couplings of aryl iodides to phosphinate lead directly to the target protected bis-amino acid. Controlled peptide coupling of the new bis-amino acid is also demonstrated.

  DOI：

  10.1021/jo00094a036

文献信息

• Late Stage Phosphotyrosine Mimetic Functionalization of Peptides Employing Metallaphotoredox Catalysis
  作者：Hao Chen、Runyu Mao、Martin Brzozowski、Nghi H. Nguyen、Brad E. Sleebs

  DOI：10.1021/acs.orglett.1c01200

  日期：2021.6.4

  requires multistep syntheses, and therefore late stage incorporation of these mimetics into peptides is not feasible. Here, we develop and employ metallaphotoredox catalysis using 4-halogenated phenylalanine to afford a variety of protected pTyr mimetics in one step. This methodology was shown to be tolerant of common protecting groups and applicable to the late stage pTyr mimetic modification of protected

  获得磷酸酪氨酸 (pTyr) 模拟物需要多步合成，因此将这些模拟物后期掺入肽中是不可行的。在这里，我们使用 4-卤代苯丙氨酸开发和使用金属光氧化还原催化，一步提供各种受保护的 pTyr 模拟物。该方法显示出对常见保护基团的耐受性，并适用于受保护和未受保护肽以及具有生物相关性的肽的后期 pTyr 模拟修饰。
• Synthesis of the Side Chain Cross-Linked Tyrosine Oligomers Dityrosine, Trityrosine, and Pulcherosine
  作者：Ojia Skaff、Katrina A. Jolliffe、Craig A. Hutton

  DOI：10.1021/jo051076m

  日期：2005.9.1

  5-diiodotyrosine and tyrosine-3-boronic acid derivatives gave the corresponding trityrosine, but in low yield. However, use of a potassium tyrosine-3-trifluoroborate derivative in place of the corresponding pinacol boronate ester, in combination with protecting group variation, gave protected trityrosine in good yield. Access to pulcherosine was achieved through copper-catalyzed coupling of phenylalanine-4-boronic

  已经实现了二氢酪氨酸的有效合成以及酪氨酸三聚体三氢酪氨酸和pulcherosine的首次合成。受保护的3-碘酪氨酸串联Miyaura borylation-Suzuki偶联得到受保护的二酪氨酸。氨基甲酸苄酯，酯和醚保护基团的选择使一步式整体脱保护反应可得到二酪氨酸。受保护的3，5-二碘酪氨酸和酪氨酸-3-硼酸衍生物的Suzuki偶联产生相应的三苯甲基酪氨酸，但是收率低。然而，酪氨酸-3-三氟硼酸钾衍生物代替相应的频哪醇硼酸酯与保护基团的变化结合使用，以良好的收率得到了被保护的三苯酪氨酸。通过铜催化的苯丙氨酸-4-硼酸和4- O的偶联反应获得了pulcherosine。-保护的多巴衍生物，得到异碘酪氨酸衍生物。选择性卤化，然后与酪氨酸-3-三氟硼酸钾铃木偶联，得到保护的pulcherosine。对被保护的三苯甲基酪氨酸和普卢切洛因衍生物的整体脱保护完成了相应的tris-α-氨基酸的第一合成。
• Synthesis and binding studies of two new macrocyclic receptors for the stereoselective recognition of dipeptides
  作者：Ana Maria Castilla、M Morgan Conn、Pablo Ballester

  DOI：10.3762/bjoc.6.5

  日期：——

  We present here the design, synthesis, and analysis of a series of receptors for peptide ligands inspired by the hydrogen-bonding pattern of protein β-sheets. The receptors themselves can be regarded as strands 1 and 3 of a three-stranded β-sheet, with cross-linking between the chains through the 4-position of adjacent phenylalanine residues. We also report on the conformational equilibria of these receptors in solution as well as on their tendency to dimerize. ¹H NMR titration experiments are used to quantify the dimerization constants, as well as the association constant values of the 1:1 complexes formed between the receptors and a series of diamides and dipeptides. The receptors show moderate levels of selectivity in the molecular recognition of the hydrogen-bonding pattern present in the diamide series, selecting the α-amino acid-related hydrogen-bonding functionality. Only one of the two cyclic receptors shows modest signs of enantioselectivity and moderate diastereoselectivity in the recognition of the enantiomers and diastereoisomers of the Ala-Ala dipeptide (ΔΔG⁰₁ (DD-DL) = −1.08 kcal/mol and ΔΔG⁰₁ (DD-LD) = −0.89 kcal/mol). Surprisingly, the linear synthetic precursors show higher levels of stereoselectivity than their cyclic counterparts.

  我们在这里介绍了一系列受蛋白质β-折叠中氢键模式启发的肽配体受体的设计、合成和分析。这些受体本身可以被视为一个三股β-折叠中的第一股和第三股，通过相邻苯丙氨酸残基的4位交联链之间的交联。我们还报告了这些受体在溶液中的构象平衡以及它们二聚的倾向。使用1H NMR滴定实验来量化二聚化常数，以及受体和一系列二酰胺和二肽形成的1:1复合物的关联常数值。这些受体在分子识别二酰胺系列中存在的氢键模式方面表现出适度的选择性，选择α-氨基酸相关的氢键功能。仅有两个环状受体中的一个显示出对Ala-Ala二肽的对映体和对映异构体的识别中适度的对映选择性和中等的顺反异构选择性（ΔΔG01（DD-DL）= -1.08 kcal/mol和ΔΔG01（DD-LD）= -0.89 kcal/mol）。令人惊讶的是，线性合成前体显示出比它们的环状对应物更高的立体选择性。
• Dual‐Mechanism Quenched Fluorogenic Probe Provides Selective and Rapid Detection of Cathepsin L Activity**
  作者：Kelton A. Schleyer、Ben Fetrow、Peter Zannes Fatland、Jun Liu、Maya Chaaban、Biwu Ma、Lina Cui

  DOI：10.1002/cmdc.202000823

  日期：2021.4.8

  have developed a fluorogenic probe, CTLAP, that displays good selectivity for CTL over CTB and CTV while exhibiting low background fluorescence attributed to dual quenching mechanisms. CTLAP achieves optimum CTL selectivity in the first 10 min of incubation, thus suggesting that it is amenable for rapid detection of CTL, even in the presence of competing cathepsins.

  组织蛋白酶 L (CTL) 是一种半胱氨酸蛋白酶，在许多疾病状态下活性上调。重叠的底物特异性使得 CTL 活性的选择性检测难以从其密切同源物 CTV 和普遍存在的 CTB 的活性中解析出来。由于对比度较差或需要额外的检测步骤来实现选择性，当前的 CTL 活性探针的应用受到限制。我们开发了一种荧光探针 CTLAP，与 CTB 和 CTV 相比，它对 CTL 具有良好的选择性，同时由于双重猝灭机制而表现出低背景荧光。CTLAP 在孵育的前 10 分钟内即可实现最佳的 CTL 选择性，因此表明即使存在竞争性组织蛋白酶，它也适合快速检测 CTL。
• A protected l-bromophosphonomethylphenylalanine amino acid derivative (BrPmp) for synthesis of irreversible protein tyrosine phosphatase inhibitors
  作者：Naresh S. Tulsi、A. Michael Downey、Christopher W. Cairo

  DOI：10.1016/j.bmc.2010.09.040

  日期：2010.12

  Protein tyrosine phosphatases (PTPs) are important therapeutic targets for medicinal chemists and biochemists. General strategies for the development of inhibitors of these enzymes are needed. Several modular strategies which rely on phosphotyrosine mimics are known for PTP inhibitors. Previous strategies include phosphonomethylphenylalanine (Pmp) derivatives which act as competitive inhibitors. Pmp amino acid derivatives have been used to develop specific inhibitors by incorporation into sequences recognized by the PTP of interest. We report the synthesis of a new phosphonotyrosine analog, L-phosphonobromomethylphenylalanine (BrPmp), which acts as an inhibitor of PTPs. The BrPmp derivative was prepared as an Fmoc-protected amino acid which can be used in standard solid phase peptide synthesis (SPPS) methods. The synthesis of the protected amino acid derivative requires 11 steps from tyrosine with a 30% overall yield. Enzyme inhibition studies with the PTP CD45 demonstrate that BrPmp derivatives are irreversible inhibitors of the enzyme. A tripeptide which incorporated BrPmp had increased inhibitory potency against PTP relative to BrPmp alone, confirming that the incorporation of BrPmp into peptide sequences provides additional context to improve enzyme binding. (c) 2010 Elsevier Ltd. All rights reserved.