N-tert-butoxycarbonyl-L-leucyl-L-methioninamide | 2280-68-4

• 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
• 英文名称: N-tert-butoxycarbonyl-L-leucyl-L-methioninamide
• 英文别名: (S,S)-N-(tert-butoxycarbonyl)leucylmethionine amide；Boc-LeuΨ(CH2NH)Met-NH2；BOC-L Leu-L Met-NH2；BOC-Leu-Met-NH2；Boc-L-Leu-methionamid；tert-butyl N-[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate
• CAS: 2280-68-4
• 化学式: C₁₆H₃₁N₃O₄S
• 分子量: 361.506
• InChiKey: OJANTFFQNUJOQL-RYUDHWBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  24
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  136
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-tert-butoxycarbonyl-L-leucyl-L-methioninamide 在 苯甲醚 、 三氟乙酸 、 氯甲酸异丁酯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 pyroglutamyl-phenylalanyl-phenylalanine-glycyl-leucyl-methionine amide
  参考文献：
  名称：

  Activity of the C-terminal part of substance P on guinea pig ileum and trachea preparations I. N-acylated pentapeptides SP(7–11)

  摘要：

  DOI：

  10.1016/0223-5234(88)90006-2
• 作为产物：
  描述：

  Boc-L-蛋氨酸 在 N-甲基吗啉 、 氨 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 2.0h， 生成 N-tert-butoxycarbonyl-L-leucyl-L-methioninamide
  参考文献：
  名称：

  人组织蛋白酶F与二肽腈抑制剂的活性位点图。

  摘要：

  恒定链的切割是主要组织相容性复合体II类的运输途径中的关键事件。组织蛋白酶S是恒定链的主要加工酶，但是组织蛋白酶F在巨噬细胞中作为其功能增效剂起作用，其在恒定链切割中与组织蛋白酶S一样有效。尚未开发出针对组织蛋白酶F的专用低分子量抑制剂。用52个二肽腈作为共价可逆抑制剂进行反应，绘制了一个活性位点图，以绘制人组织蛋白酶F非引物结合区的结构-活性关系。在逐步过程中，设计了具有优化片段组合的新化合物，并合成的。在人半胱氨酸组织蛋白酶F，B，L，K和S上评估了这些二肽腈。化合物10（ñ - （4-苯基苯甲酰基）-leucylglycine腈）和12（ñ - （4-苯基苯甲酰基）leucylmethionine腈）被认为是人类的有效抑制剂的组织蛋白酶F，其ķ我值<10N的中号。利用我们研究中的所有二肽腈，生成了3D活动图，以可视化此系列组织蛋白酶F抑制剂的结构与活性之间的关系。

  DOI：

  10.1002/cmdc.201500151

文献信息

• Palladium-catalyzed reaction of tributyltin hydride. Selective and very mild deprotection of allyl and allyloxycarbonyl derivatives of amino-acids.
  作者：F Guibe、O Dangles、G Balavoine

  DOI：10.1016/s0040-4039(00)84530-x

  日期：——

  Allyl(All) and Allyloxycarbonyl(Alloc) amino-acid derivatives are deprotected through palladium-catalyzed hydrostannolysis by Bu3SnH in a highly selective manner. Benzyl and benzyloxycarbonyl groups are stable under these conditions. Moreover the allyl and Alloc groups seem orthogonal to the t-butyl and t-butoxycarbonyl protecting groups.

  烯丙基（All）和烯丙氧基羰基（Alloc）氨基酸衍生物通过Bu 3 SnH以高选择性的方式通过钯催化的氢化锡烷基水解进行脱保护。苄基和苄氧羰基在这些条件下是稳定的。此外，烯丙基和Alloc基团似乎与叔丁基和叔丁氧羰基保护基团正交。
• Optimum Cross-linking Spacer Length of Dimeric Neurokinin B Analogs for Interaction with NK-1 Tachykinin Receptors.
  作者：Hiroshi Matsumoto、Yasuyuki Shimohigashi、Yukio Takano、Kazuyasu Sakaguchi、Hiro-o Kamiya、Motonori Ohno

  DOI：10.1246/bcsj.66.196

  日期：——

  A series of dimeric analogs of neurokinin B (NKB) COOH-terminal heptapeptide were synthesized in order to find an optimum length of cross-linking spacer for bivalent interaction with tachykinin receptors. Dimerization was carried out at the NH2-terminus of heptapeptide with succinyl bis[(Gly)n–OH], in which the number of glycine varies from 0 to 4. Dimers D–(Gly)n–NKB4—10, namely succinyl bis[(Gly)n–Asp–Ser–Phe–Val–Gly–Leu–Met–NH2] (n = 0—4), were almost inactive in the assay using rat vas deferens, indicating that they have no interaction with NK-2 receptor subtype. In contrast, these dimers were very active in guinea pig ileum (GPI) containing all of NK-1, 2, and 3 receptors. Relative activity was highest when the cross-linking spacer with oligoglycine of n = 2, and decreased sharply for dimers with shorter and longer chain lengths (n = 0 and 1; 3 and 4). In order to specify receptor subtype (NK-1 or NK-3) in GPI to which dimers bind, dimers were examined under the conditions that NK-1 receptors are desensitized by substance P methyl ester. All dimers exhibited drastically diminished contractile activity, indicating that dimers exclusively interact with NK-1. This was further confirmed by blocking the response of NK-3 receptors with atropine, which had no effect on the contractile activity of dimers. The results suggested that dimers interact bivalently with NK-1 receptors by bridging adjacent two binding sites.

  为寻找与速激肽受体二价相互作用的最佳连接间隔长度，合成了一系列神经激肽B（NKB）羧基端七肽的二聚体类似物。通过琥珀酰双[甘氨酸（n）—OH]在七肽的氨基端进行二聚化，其中甘氨酸的数目从0到4变化。二聚体D–（甘氨酸）n–NKB4—10，即琥珀酰双[甘氨酸（n）–天冬氨酸–丝氨酸–苯丙氨酸–缬氨酸–甘氨酸–亮氨酸–蛋氨酸–NH2]（n = 0—4），在利用大鼠输精管进行的实验中几乎无活性，表明它们与NK-2受体亚型无相互作用。相比之下，这些二聚体在含有所有NK-1、NK-2和NK-3受体的大鼠回肠（GPI）中非常活跃。当连接间隔为n = 2的寡甘氨酸时，相对活性最高，而链长更短和更长的二聚体（n = 0和1；3和4）活性显著降低。为了明确二聚体在GPI中结合的受体亚型（NK-1或NK-3），在NK-1受体被甲酯化的P物质脱敏的条件下检测了二聚体。所有二聚体的收缩活性都急剧降低，表明二聚体专门与NK-1受体相互作用。进一步通过利用阿托品阻断NK-3受体的反应，证实了这一点，阿托品对二聚体的收缩活性没有影响。结果表明，二聚体通过桥接相邻的两个结合位点与NK-1受体发生二价相互作用。
• Synthesis and Biological Evaluation of Dehydrophenylalanine Containing Substance P Fragments
  作者：Paramjeet Kaur、Gyanedra Kumar Patnaik、Ram Raghubir、Virander Singh Chauhan

  DOI：10.1246/bcsj.65.3412

  日期：1992.12

  Peptide fragments of Substance P corresponding to the C-terminal segments (6-11) and (4-11), which contain a putative β-turn, were synthesised using solution phase methodology. Analogs of Substance P were synthesised where the phenylalanine residue at position 8 was replaced by dehydrophenylalanine (ΔPhe) and the glycine residue in position 9 was replaced by alanine, valine, sarcosine (N–Me–Gly) and α-aminoisobutyric acid. In two of the analogs [8-ΔPhe, 9-Sar]–SP (4-11) (5) and [5,8-ΔPhe, 9-Aib]–SP (4-11) (7) glutamine residue at position 5 was also substituted by ΔPhe. These analogs were evaluated for their ability to cause smooth muscle contraction in guinea pig ileum preparation (in vitro) and for hypotensive activity (in vivo) in female rats anesthetized with urethane. In the hexapeptide series [8-ΔPhe]–SP (6-11) (1) and [8-ΔPhe, 9-Sar]–SP (6-11) (4) showed significant activity in both the assays. Octapeptide [5,8-ΔPhe, 9-Sar]–SP (4-11) (5) with ΔPhe residue in positions 5 and 8 and sarcosine in position 9 was found to be the most potent analog both in vitro and in vivo systems.

  合成了与物质P的C端片段（6-11）和（4-11）相对应的肽段，这些片段包含一个假定的β-转角，采用溶液相的方法。合成了物质P的类似物，其中第8位的苯丙氨酸残基被脱氢苯丙氨酸（ΔPhe）替代，第9位的甘氨酸残基被丙氨酸、缬氨酸、肌氨酸（N–Me–Gly）和α-氨基异丁酸替代。在两个类似物[8-ΔPhe, 9-Sar]–SP (4-11) (5)和[5,8-ΔPhe, 9-Aib]–SP (4-11) (7)中，第5位的谷氨酰胺残基也被ΔPhe替代。这些类似物在豚鼠回肠制备中（体外）评估了其引起平滑肌收缩的能力，并在以氨基甲酸酯麻醉的雌性大鼠中评估了其降血压活性。在六肽系列中，[8-ΔPhe]–SP (6-11) (1)和[8-ΔPhe, 9-Sar]–SP (6-11) (4)在两项实验中均显示出显著的活性。八肽[5,8-ΔPhe, 9-Sar]–SP (4-11) (5)在第5和第8位具有ΔPhe残基并在第9位含有肌氨酸，发现其在体外和体内系统中是最有效的类似物。
• Synthesis and biological activity of substance P C-terminal hexapeptide analogues: structure-activity studies
  作者：Constantine Poulos、John R. Brown、Christopher C. Jordan

  DOI：10.1021/jm00157a028

  日期：1986.7

  series of analogues of the C-terminal hexapeptide of substance P, modified at the glutaminyl residue, was synthesized and their relative activities as spasmogens were determined in the guinea pig ileum and rat colon muscularis mucosae preparations in vitro. In general, when compared to SP6-11, the loss of the carboxamide group has little effect on activity in the colon and reduces activity on the ileum

  合成了一系列在谷氨酰胺残基上修饰的物质P的C端六肽类似物，并在体外确定了豚鼠回肠和大鼠结肠粘膜黏膜制剂中作为痉挛源的相对活性。通常，与SP6-11相比，羧酰胺基的丢失对结肠的活性影响很小，而对回肠的活性降低。例外的是Orn6类似物，它在两种制剂中均具有活性，被提议作为结构活性研究的有用工具。结论是6位取代基的氢键电势可能是生物活性的重要决定因素。
• Studies on peptides. CXIV. Synthesis of hylambates-kassinin, a frog skin tachykinin peptide.
  作者：NOBUTAKA FUJII、SHINICHI KATAKURA、HARUAKI YAJIMA、YOSHIHIRO NAKATA、ATSUKO INOUE、TOMIRO SEGAWA

  DOI：10.1248/cpb.31.4259

  日期：——

  Hylambates-kassinin, a new amphibian skin dodecapeptide of the tachykinin family, was synthesized in a conventional manner using thioanisole-mediated deprotection with trifluoromethanesulfonic acid. The contractile potency of synthetic hylambates-kassinin in isolated guinea-pig duodenum was 1.4 times higher than that of synthetic kassinin.

  Hylambates-kassinin是一种新的两栖动物皮肤十二肽，属于速激肽家族。它采用传统方法合成，使用了以硫醚为介质的去保护反应，辅以三氟甲烷磺酸。合成的Hylambates-kassinin在孤立的豚鼠十二指肠中的收缩效力是合成的kassinin的1.4倍。