BOC-L-Leu-D-Ala-OH | 374116-21-9

• 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: BOC-L-Leu-D-Ala-OH
• 英文别名: t-Boc-Leu-D-Ala-OH；Boc-L-Leu-D-Ala；D-Alanine, N-[(1,1-dimethylethoxy)carbonyl]-L-leucyl-；(2R)-2-[[(2S)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]propanoic acid
• CAS: 374116-21-9
• 化学式: C₁₄H₂₆N₂O₅
• 分子量: 302.371
• InChiKey: DQXXTKCYGQDBKO-ZJUUUORDSA-N

物化性质

• 沸点：
  502.5±35.0 °C(Predicted)
• 密度：
  1.104±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 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：

  BOC-L-Leu-D-Ala-OH 在 palladium on activated charcoal N-羟基-7-氮杂苯并三氮唑 、 氢气 、 碳酸氢钠 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 3-(二乙氧基邻酰氧基)-1,2,3-苯并三嗪-4-酮 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 50.5h， 生成 Fmoc-L-Dab(Boc-L-Leu-D-Ala-L-Chp)-OBn
  参考文献：
  名称：

  Total Synthesis and Examination of Three Key Analogues of Ramoplanin: A Lipoglycodepsipeptide with Potent Antibiotic Activity

  摘要：

  The total synthesis and evaluation of three key ramoplanin aglycon analogues are detailed. The first (5a) represents replacement of the labile depsipeptide ester with a stable amide (HAsn2 --> Dap2) with removal of the HAsn pendant carboxamide, and it was found to be slightly more potent than the natural aglycon in antimicrobial assays providing a new lead structure with an improved profile and a more stable and accessible macrocyclic template on which to conduct structure-function studies. In contrast, a second amide analogue 5b which contains a single additional methylene relative to 5a (HAsn2 --> Dab2) was found to be inactive in antimicrobial assays (>100-fold loss in activity). The third key analogue 5c in which the Asn1 lipid side chain was replaced with an acetyl group revealed that it contributes significantly to the antimicrobial activity (16-fold) of the ramoplanins, but is not essential.

  DOI：

  10.1021/ja039671y
• 作为产物：
  描述：

  benzyl (tert-butoxycarbonyl)-L-leucyl-D-alaninate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 5.0h， 生成 BOC-L-Leu-D-Ala-OH
  参考文献：
  名称：

  Application of an Automated Synthesis Suite to Parallel Solution-Phase Peptide Synthesis.

  摘要：

  使用一套自主研发的自动化合成系统，制备了72个四肽衍生物库，这些是用于合成具有药物吸引力的五肽的起始材料，采用了一种汇聚策略。首先，利用自动化合成工作站大规模（100-1000克）合成了18种二肽，然后使用自动化系统在中等规模（5-10克）合成了72种四肽。每个二肽或四肽均在单个操作周期中使用改良的甲磺酸方法制备，随后在小型规模（100毫克-1克）下利用机器人工作站并行合成了56种五肽的子库。

  DOI：

  10.1248/cpb.49.1147

文献信息

• Total Synthesis of the Ramoplanin A2 and Ramoplanose Aglycon
  作者：Wanlong Jiang、Jutta Wanner、Richard J. Lee、Pierre-Yves Bounaud、Dale L. Boger

  DOI：10.1021/ja020237q

  日期：2002.5.1

  subunits composed of residues 3−9 (heptapeptide 15), pentadepsipeptide 26, and pentapeptide 34 (residues 10−14) were prepared, sequentially coupled, and cyclized to provide the 49-membered depsipeptide core of the aglycon. Key to the preparation of the pentadepsipeptide 26 incorporating the backbone ester was the asymmetric synthesis of an orthogonally protected l-threo-β-hydroxyasparagine and the development

  公开了ramoplanin A2和ramoplanose苷元的会聚全合成。制备由残基 3-9（七肽 15）、五肽 26 和五肽 34（残基 10-14）组成的三个关键亚基，依次偶联并环化以提供苷元的 49 元缩酚肽核心。制备包含主链酯的五肽 26 的关键是正交保护的 l-苏式-β-羟基天冬酰胺的不对称合成，以及为其受阻醇（EDCI、DMAP、0 ℃）。选择偶联位点以最大限度地提高合成的收敛性，包括三个亚基的收敛性，以防止羧酸盐活化的苯基甘氨酸衍生残基的晚期外消旋化，并为 49 元环闭合争取无环大环化底物的 β-折叠预组织。因此，所选 Phe9-d-Orn10 位点的大环化可能受益于...
• Alanine Scan of [<scp>l</scp>-Dap²]Ramoplanin A2 Aglycon:  Assessment of the Importance of Each Residue
  作者：Joonwoo Nam、Dongwoo Shin、Yosup Rew、Dale L. Boger

  DOI：10.1021/ja068573k

  日期：2007.7.1

  ramoplanin A2 aglycon, a potent antibiotic that inhibits bacterial cell wall biosynthesis, is detailed. As a consequence of both its increased stability (lactam vs lactone) and its "relative" ease of synthesis, the alanine scan was conducted on [Dap2]ramoplanin A2 aglycon, which possesses antimicrobial activity equal to or slightly more potent than that of ramoplanin A2 or its aglycon. Thus, 14 key

  在定义每个残基的重要性并确定分子的关键区域的工作中，详细介绍了 ramoplanin A2 苷元的丙氨酸扫描，这是一种抑制细菌细胞壁生物合成的强效抗生素。由于其稳定性（内酰胺与内酯）的增加及其“相对”易于合成，对 [Dap2] 雷莫拉宁 A2 苷元进行了丙氨酸扫描，其具有与雷莫拉宁 A2 相同或略强的抗菌活性或其苷元。因此，制备了 ramoplanin A2 苷元的 14 个关键类似物，代表残基 3-13、15 和 17 的扫描，采用收敛的溶液相全合成，将努力巩固到可管理的水平。
• Himaja; Desai, Siddharth; Sambanthan, A. Thirugnana, Asian Journal of Chemistry, 2010, vol. 22, # 4, p. 2914 - 2918
  作者：Himaja、Desai, Siddharth、Sambanthan, A. Thirugnana、Ranjitha

  DOI：——

  日期：——
• Cyclotetrapeptides with alternating d-Ala residues: synthesis and spectroscopic studies
  作者：Maria Ngu-Schwemlein、Zhe Zhou、Toni Bowie、Rebecca Eden

  DOI：10.1016/s0022-2860(03)00207-2

  日期：2003.7

  Three cyclotetrapeptides, c[Leu-D-Ala-Xaa-D-Ala], where Xaa is Leu (P1), Lys (P2) and Glu (P3) were synthesized and studied by H-1 and C-13 NMR and CD spectroscopy. These cyclotetrapeptides exhibit similar coupling constants, (3)J(HNHalpha), in the range of 8.56-9.93 Hz, commonly observed for beta-turn structures. All amide proton chemical shifts for P1, P2 and P3 exhibited linear dependence on temperature with moderate temperature coefficients ranging from -3.1 to -9.8 ppb/K. Amide proton signal broadening was observed for all residues in P1, P2 and P3, indicating that they are solvent accessible. The number of resonance observed for P1 was half of the total counts, indicating a C2 symmetric conformation. P2 and P3 exhibit similar CD in solvents of varying dielectric constants and dilutions, with characteristic positive CD bands at ca. 210 and 222 nm, which correspond to a beta-turn type structure. Small CD/temperature effect was also observed with isodichroic points, consistent with conformational stability and a well-populated cyclotetrapeptide energy state. These heterochiral cyclotetrapeptides consisting of alternating D-Ala residues adopt stabilized open beta-turn conformations and may be useful as a ligand template for further functionalization. (C) 2003 Elsevier Science B.V. All rights reserved.
• Leucinostatin Y: A Peptaibiotic Produced by the Entomoparasitic Fungus <i>Purpureocillium lilacinum</i> 40-H-28
  作者：Isao Momose、Takefumi Onodera、Hiroyasu Doi、Hayamitsu Adachi、Masatomi Iijima、Yohko Yamazaki、Ryuichi Sawa、Yumiko Kubota、Masayuki Igarashi、Manabu Kawada

  DOI：10.1021/acs.jnatprod.8b00839

  日期：2019.5.24

  Leucinostatin Y, a new peptaibiotic, was isolated from the culture broth of the entomoparasitic fungus Purpureocillium lilacinum 40-H-28. The planar structure was elucidated by detailed analysis of its NMR and MS/MS data. The absolute configurations of the amino acids were partially determined by an advanced Marfey's method. The biological activities of leucinostatin Y were assessed using human pancreatic cancer cells, revealing the importance of the C-terminus of leucinostatins for preferential cytotoxicity to cancer cells under glucose-deprived conditions and inhibition of mitochondrial function.