N-Me-Leu-OBzl p-toluenesulfonic acid salt

• 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-Me-Leu-OBzl p-toluenesulfonic acid salt
• 英文别名: MeLeu-OBzl p-tosylate；N-methylleucine benzyl ester p-TsOH salt；N-methyl-L-leucine benzyl ester p-toluenesulfonate；N-Me-Leu-OBn p-TsOH salt；H-N-Me-L-Leu-OBn*TosOH；PTS HMeN-Leu-OBn；pTos MeN-Leu-OBn；N-ME-Leu-obzl P-tosylate；benzyl (2S)-4-methyl-2-(methylamino)pentanoate;4-methylbenzenesulfonic acid
• 化学式: C₇H₈O₃S*C₁₄H₂₁NO₂
• mdl: MFCD00083659
• 分子量: 407.531
• InChiKey: HQAGSSPEDLUVSS-ZOWNYOTGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.98
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-Me-Leu-OBzl p-toluenesulfonic acid salt 在 palladium on activated charcoal 氢气 、 benzotriazol-1-yloxy-tris(dimethylamino)-phosphonium chloride 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 octanoyl-N-methylleucine
  参考文献：
  名称：

  小分子B的合成研究

  摘要：

  使用节段缩合策略合成了从山茱Lyn（Lyngbya majuscula）分离的脂肽微柱蛋白B的辛酰基和去乙酰基类似物。为了实现这一点，在五步合成中由Boc-Pro-Ala-OH制备了独特的1-prolyl-甲基-2-pyrroline单元。使用PyBoP®将该片段偶联至二肽Boc-Thr-MeVal-OH。脱保护，然后由PyBroP®介导的与辛酰基-MeLeu-OH偶联，最终形成了去乙酰基微考林B的辛酰基类似物。

  DOI：

  10.1016/0040-4020(95)00922-1
• 作为产物：
  描述：

  N-t-butoxycarbonyl-N-methyl-L-leucine 、 对甲苯磺酸 、 苯甲醇 以 甲苯 为溶剂， 反应 0.01h， 生成 N-Me-Leu-OBzl p-toluenesulfonic acid salt
  参考文献：
  名称：

  MW‐Enhanced High‐Speed Deprotection of Boc Group Usingp‐TsOH and Concommitant Formation ofN‐Me‐Amino Acid Benzyl Esterp‐TsOH Salts

  摘要：

  A high-speed, complete deprotection of Boc group from Boc amino acids and protected peptide esters employing p-TsOH in toluene under microwave irradiation is found to be complete in 30 s. The deprotection can be carried out in methanol and acetonitrile also. Under the present conditions, C-peptide benzyl esters and O-benzyl ethers have been found to be stable. This has permitted us to carry out the synthesis of [Leu] enkephalin employing the Boc/Bzl-group strategy. Further more, it has been found that both N-alpha-Fmoc and N-alpha-Z groups are completely stable. The present conditions can be extended for the concomitant removal of the Boc group and the formation of C-benzyl amino acid esters as well. This has been utilized for the synthesis of N-Me amino acid benzyl esters starting from Boc-N-Me amino acids in a single step.

  DOI：

  10.1081/scc-200063953

文献信息

• Total Synthesis of Pleofugin A, a Potent Inositol Phosphorylceramide Synthase Inhibitor
  作者：Toshihiro Kiho、Mizuka Yokoyama、Hiroshi Kogen

  DOI：10.1021/acs.orglett.8b01930

  日期：2018.8.3

  X-ray analysis and total synthesis of 1 unambiguously confirmed pleofingin A’s absolute configuration. The total synthesis was achieved by convergent assembly of three fragments (12, 14, and 18). This synthetic approach provides access to derivatives of 1 to search for antifungal agents that will be more effective in clinical use.

  X射线分析和1的全合成明确证实了pleofingin A的绝对构型。总合成通过的三个片段（会聚组件实现12，14，和18）。这种合成方法可提供1的衍生物，以寻找在临床上更有效的抗真菌剂。
• Synthetic Modification within the “RPRL” Region of Apelin Peptides: Impact on Cardiovascular Activity and Stability to Neprilysin and Plasma Degradation
  作者：Shaun M. K. McKinnie、Wang Wang、Conrad Fischer、Tyler McDonald、Kevin R. Kalin、Xavier Iturrioz、Catherine Llorens-Cortes、Gavin Y. Oudit、John C. Vederas

  DOI：10.1021/acs.jmedchem.7b00723

  日期：2017.7.27

  (NEP). The synthetic analogues modified within the NEP degradation site (“RPRL” motif) showed improved in vitro proteolytic stability while maintaining receptor-binding affinities, with three candidate peptides retaining full cardiovascular activities for potential therapeutic application. Many such analogues proved physiologically inactive even with relatively conservative modifications, highlighting

  Apelin是一种重要的哺乳动物肽激素，具有多种生理作用，尤其是在心血管系统中。Apelinergic系统是治疗疾病的有希望的靶标，但是由于蛋白酶（包括NEPrilysin（NEP））对apelin衍生的肽进行了快速蛋白水解，因此仍有待实现。在NEP降解位点（“ RPRL”基序）内修饰的合成类似物显示出改善的体外蛋白水解稳定性，同时保持受体结合亲和力，其中三种候选肽保留了完整的心血管活性，可用于潜在的治疗应用。即使具有相对保守的修饰，许多此类类似物也被证明在生理上是无活性的，从而突显了该区域对于该肽激素的完全激动剂活性的重要性。
• Antineoplastic activity of linear leucine homodipeptides and their potential mechanisms of action
  作者：Yun Lei、Xiao-Xia Yang、Wei Guo、Fu-yong Zhang、Xiao-Jian Liao、Hui-Fu Yang、Shi-Hai Xu、Sheng Xiong

  DOI：10.1097/cad.0000000000000615

  日期：2018.7

  cleavage of caspase-9 and caspase-3, as well as increased intracellular Ca levels and decreased the mitochondrial membrane potential. Collectively, certain linear leucine dipeptides derived from cyclic pentapeptide are able to inhibit tumor cell proliferation through cell cycle arrest and apoptosis induction. The N-methyl group in the side chain and the D/L conformation of the amino-acid residue are critical

  Galaxamide是一种稀有的环状同五肽，由从海水藻类Galaxaura silkosa分离出的三个亮氨酸和两个N-甲基亮氨酸组成。该化合物的强大抗肿瘤活性使其成为肿瘤治疗的有希望的候选者。然而，galaxamide的合成是一个复杂的过程，并且水溶性差。根据其特殊的化学组成，我们设计了一系列线性亮氨酸同系肽。在七个二肽衍生物中，具有末端保护基团和酰胺基团中氢的甲基取代基的五个化合物显示出对各种癌细胞的显着抑制作用。N-叔丁基-D-亮氨酸-N-甲基-D-亮氨酸苄基（A7）是由两个D-亮氨酸缩合而成的唯一立体异构体，具有最高的抗肿瘤活性。经A7处理的细胞表现出细胞周期停滞和典型的经历凋亡的细胞形态变化。Annexin-V阳性/碘化丙啶阴性细胞的数量也增加，表明诱导了早期凋亡。A7促进caspase-9和caspase-3的裂解，并增加细胞内Ca水平并降低线粒体膜电位。集体地，衍生自环状五肽的
• <i>N</i>-Methylamino Acids in Peptide Synthesis. IV. Racemization and Yields in Peptide-bond Formation
  作者：John R. McDermott、N. Leo Benoiton

  DOI：10.1139/v73-386

  日期：1973.8.1

  observed when Z-Ala-MeLeu was coupled with Gly-OBzl by various methods in the presence of salts such as triethylamine hydrochloride or p-toluenesulfonate. Only coupling through the N-hydroxysuccinimide (HONSu) ester gave stereochemically pure product. In the absence of salt, less racemization was observed, but only couplings using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline and N,N′-dicyclohexylcarbod

  使用 Ala-MeLeu-Gly 和 Ala-MeLeu 作为模型肽研究了肽键形成和混合酸酐活化过程中 N-甲基氨基酸残基的外消旋化。将结果与 Ala-Leu-Gly、Ala-Leu 和 Ala-Pro 的结果进行比较。外消旋化的程度通过使用氨基酸分析仪分析脱保护后反应的非对映产物来确定。在 Bz-MeLeu、Z-Ala-MeLeu 和 Z-Ala-Leu 的混合酸酐水解后检测到广泛的外消旋化，但 Boc-Ala-Pro 和 Z-MeIle 没有。当 Z-Ala-MeLeu 与 Gly-OBzl 在盐（如三乙胺盐酸盐或对甲苯磺酸盐）存在下通过各种方法偶联时，观察到显着的外消旋化（2.8-39%）。只有通过 N-羟基琥珀酰亚胺 (HONSu) 酯偶联才能得到立体化学纯的产物。在没有盐的情况下，观察到较少的外消旋化，但仅使用 N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline
• In vitro evaluation of N-methyl amide tripeptidomimetics as substrates for the human intestinal di-/tri-peptide transporter hPEPT1
  作者：Rikke Andersen、Carsten Uhd Nielsen、Mikael Begtrup、Flemming Steen Jørgensen、Birger Brodin、Sven Frokjaer、Bente Steffansen

  DOI：10.1016/j.ejps.2006.03.007

  日期：2006.7

  oral absorption of tripeptides is generally mediated by the human intestinal di-/tri-peptide transporter, hPEPT1. However, the bioavailability of tripeptides is often limited due to degradation in the GI-tract by various peptidases. The aim of the present study was to evaluate the general application of N-methyl amide bioisosteres as peptide bond replacements in tripeptides in order to decrease degradation by peptidases and yet retain affinity for and transport via hPEPT1. Seven structurally diverse N-methyl amide tripeptidomimetics were selected based on a principal component analysis of structural properties of 6859 N-methyl amide tripeptidomimetics. In vitro extracellular degradation of the selected tripeptidomimetics as well as affinity for and transepithelial transport via hPEPT1 were investigated in Caco-2 cells. Decreased apparent degradation was observed for all tripeptidomimetics compared to the corresponding natural tripeptides. However, affinity for and transepithelial transport via hPEPT1 were only seen for Gly-Sar-Sar, Asn Psi[CONCH3]Phe Psi[CONCH3]Trp, and Gly-Sar-Leu. This implies that tripeptidomimetics originating from tripeptides with neutral side chains are more likely to be substrates for hPEPT1 than tripeptidomimetics with charged side chains. The results of the present study indicate that the N-methyl amide peptide bond replacement approach for increasing bioavailability of tripeptidomimetic drug candidates is not generally applicable to all tripeptides. Nevertheless, retained affinity for and transport via hPEPT1 were shown for three of the evaluated N-methyl amide tripeptidomimetics. (c) 2006 Elsevier B.V All rights reserved.