叔-丁基氧羰基-甘氨酰苯丙氨酸 | 4530-37-4

• 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: 叔-丁基氧羰基-甘氨酰苯丙氨酸
• 英文名称: N-t-butyloxycarbonylglycyl-L-phenylalanine
• 英文别名: Boc-Gly-Phe-OH；tert-Butyloxycarbonyl-glycylphenylalanine；(2S)-2-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]amino]-3-phenylpropanoic acid
• CAS: 4530-37-4
• 化学式: C₁₆H₂₂N₂O₅
• 分子量: 322.361
• InChiKey: DBYCQNCOYVUBGY-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  叔-丁基氧羰基-甘氨酰苯丙氨酸 在 sodium hydroxide 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 为溶剂， 反应 8.0h， 生成 (2S)-4-methyl-2-[methyl-[(2S)-2-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]amino]-3-phenylpropanoyl]amino]pentanoic acid
  参考文献：
  名称：

  Investigation of the structural parameters involved in the .mu. and .delta. opioid receptor discrimination of linear enkephalin-related peptides

  摘要：

  The previous rules proposed for selective recognition of mu and delta opioid receptors by modified enkephalins were investigated through an extensive structure-activity study. Thus, modifications of the sequence of TRIMU 4 (Tyr-D-Ala-Gly-NHCH(CH3)CH2CH(CH3)2, a peptide that exhibits mu selectivity close to that of DAGO (Try-D-Ala-Gly-N(Me)Phe-Gly.ol), were performed for two positions, 2 and 4, critical for mu recognition. The drastic loss of potency following introduction of L-Ala or Aib in position 2 emphasizes the importance of the stereochemistry and the steric size of the X2 amino acid for optimal mu binding. The enhancement of the intrinsic flexibility of the C-terminal alkyl chain of TRIMU 4 through removal of a methyl group leads to TRIMU 5 (Tyr-D-Ala-Gly-NHCH2CH2CH(CH3)2), a peptide with a mu selectivity similar to that of DAGO. In contrast, introduction of an O-tert-butyl Ser2 residue increases affinity for delta receptors. In the hexapeptide series derived from DSLET (Tyr-D-Ser-Gly-Phe-Leu-Thr), a D-Thr2 moiety was shown to be very efficient in improving delta recognition and delta selectivity appeared also to be modulated by the nature of the sixth residue. The potencies of the 24 peptides studied to inhibit the electrically evoked contractions of the GPI or MVD are relatively well correlated with their affinities for brain mu or delta receptors labeled with [3H]DAGO or [3H]DSLET, respectively. Moreover, the analgesic potency (hot plate test) of the peptides is related to their affinity for rat brain mu receptors. The wide range of receptor affinities exhibited by the compounds reported here could be useful to study the physiological role of mu and delta receptors.

  DOI：

  10.1021/jm00397a019
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 生成 叔-丁基氧羰基-甘氨酰苯丙氨酸
  参考文献：
  名称：

  Influence of the dipeptide linker configuration on the activity of PSMA ligands

  摘要：

  DOI：

  10.1016/j.mencom.2020.11.022

文献信息

• High penetration prodrug compositions of peptides and peptide-related compounds
  申请人：Yu Chongxi

  公开号：US09248109B2

  公开（公告）日：2016-02-02

  The invention provides compositions of novel high penetration compositions (HPC) or high penetration prodrugs (HPP) of peptides and peptide-related compounds, which are capable of crossing biological barriers with higher penetration efficiency comparing to their parent drugs. The HPPs are capable of being converted to parent drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs/HPCs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPPs/HPCs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

  这项发明提供了一种新型高渗透性肽类化合物（HPC）或高渗透性前药（HPP）的组合物，这些化合物能够比其原始药物更高效地穿越生物屏障。HPP能够在穿越生物屏障后转化为原始药物或药物代谢物，从而可以治疗原始药物或代谢物所能治疗的疾病。此外，HPP/HPC能够到达原始药物可能无法进入或在目标区域提供足够浓度的区域，从而提供新颖的治疗方法。HPP/HPC可以通过各种给药途径给予受试者，例如，局部给药到疾病作用部位以高浓度给药，或者系统给药到生物体内并以更快的速率进入全身循环。
• Diphenylsilane as a coupling reagent for amide bond formation
  作者：Morgane Sayes、André B. Charette

  DOI：10.1039/c7gc02643a

  日期：——

  A simple procedure for amide bond formation using diphenylsilane as a coupling reagent is described. This methodology enables the direct coupling of carboxylic acids with primary and secondary amines, releasing only hydrogen and a siloxane as by-products. Only one equivalent of each partner is needed, providing a more sustainable amidation method producing minimal wastes. This methodology was also

  描述了使用二苯基硅烷作为偶联剂形成酰胺键的简单程序。这种方法可以使羧酸与伯胺和仲胺直接偶联，仅释放出氢和作为副产物的硅氧烷。每个合作伙伴只需要一个等价物，即可提供一种可持续性更高的酰胺化方法，从而减少浪费。通过添加Hünig碱（DIPEA）和4-二甲基氨基吡啶（DMAP），该方法还扩展到肽和内酰胺的合成。
• 9-Silafluorenyl Dichlorides as Chemically Ligating Coupling Agents and Their Application in Peptide Synthesis
  作者：Samuel J. Aspin、Sylvain Taillemaud、Patrick Cyr、André B. Charette

  DOI：10.1002/anie.201606120

  日期：2016.10.24

  A fundamentally simple, mild, and practical procedure for peptide bond formation is reported that employs a stoichiometric amount of easy‐to‐access 9‐silafluorenyl dichlorides as the coupling agent. Without initial preactivation or elaboration of the carboxylic acid or amine termini of the amino acids, the developed reagent is proposed to act through an unprecedented chemical ligation mechanism, bringing

  据报道，一种基本简单，温和且实用的肽键形成方法是采用化学计量的易于获得的9-二氟芴基二氯化物作为偶联剂。无需对氨基酸的羧酸或胺末端进行初步的预活化或精加工，就可以开发出一种通过空前的化学连接机制发挥作用的试剂，从而将两个偶联配偶体聚集在一起，然后再将其消除。因此以高收率和低至无差向异构化提供所需的酰胺或肽键。
• 2-Chloro-4,6-dimethoxy-1,3,5-triazine. A New Coupling Reagent for Peptide Synthesis
  作者：Zbigniew J. Kamiński

  DOI：10.1055/s-1987-28122

  日期：——

  In order to facilitate the purification of peptides, the new coupling reagent 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) is proposed. Due to the weakly basic properties of the triazine ring, the side products and excess coupling reagent are easily removed by washing the crude reaction product with diluted acids. CDMT enables the synthesis of di-,tri-, and pentapeptides in 75-98% yield under mild conditions and without concomitant racemization. Moreover, the reagent diminishes the formation of side products during the incorporation of serine with an unprotected hydroxy group or of N-protected ω-nitroarginine into the peptide chain.

  为了便于肽的纯化，提出了新型偶联试剂2-氯-4,6-二甲氧基-1,3,5-三嗪（CDMT）。由于三嗪环的弱碱性，副产物和过量的偶联试剂可以通过用稀酸洗涤粗反应产物轻松去除。在温和条件下且无需伴随消旋化的情况下，CDMT能够实现二肽、三肽和五肽的合成，产率高达75-98%。此外，该试剂在未保护的羟基丝氨酸或N-保护的β-硝基精氨酸并入肽链期间减少了副产物的形成。
• Solar and Visible Light Assisted Peptide Coupling
  作者：Abhaya K. Mishra、Galit Parvari、Sourav K. Santra、Andrii Bazylevich、Ortal Dorfman、Jonatan Rahamim、Yoav Eichen、Alex M. Szpilman

  DOI：10.1002/anie.202011510

  日期：2021.5.25

  novel coupling reagent in situ. The resulting coupling method is rapid, does not require dry solvents or inert atmosphere, and is compatible with all the most common amino acids and protecting groups. Peptide couplings can be run on gram‐scale, without the use of special equipment. This method has a significantly reduced environmental and financial footprint compared to standard peptide coupling reactions

  氨基酸和肽偶联剂广泛用于与药物和材料有关的领域。尽管如此，当前的肽合成仍继续依赖使用昂贵的，对水敏感的和产生废物的偶联剂，这些偶联剂通常以多步骤的顺序制备且过量使用。本文描述了一种肽偶联反应设计，该设计在机械上依赖于4-二甲氨基吡啶-烷基卤化物电荷转移复合物的阳光激活，从而原位生成新型偶联剂。所得的偶联方法快速，不需要干燥溶剂或惰性气氛，并且与所有最常见的氨基酸和保护基兼容。肽偶联可以以克为单位运行，而无需使用特殊设备。与标准的肽偶联反应相比，该方法的环境和经济足迹显着减少。实验和计算研究支持所提出的机制。