Fmoc-L-Asn(Trt)-L-Dap(Boc-L-Leu-D-Ala-L-Chp)-OH | 668985-60-2

• 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: Fmoc-L-Asn(Trt)-L-Dap(Boc-L-Leu-D-Ala-L-Chp)-OH
• 英文别名: Fmoc-L-Asn(Trt)-L-(2,3-diaminopropionic acid)(Boc-L-Leu-D-Ala-L-(3-chloro-4-hydroxyphenylglycine))-OH
• CAS: 668985-60-2
• 化学式: C₆₃H₆₈ClN₇O₁₂
• 分子量: 1150.73
• InChiKey: PYBGNIUAJAAMIR-CMRNWSBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.74
• 重原子数：
  83.0
• 可旋转键数：
  23.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  279.69
• 氢给体数：
  9.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  D-Hpg-D-Orn(SES)-D-aThr-Hpg-D-Hpg-aThr-Phe-OBn 、 Fmoc-L-Asn(Trt)-L-Dap(Boc-L-Leu-D-Ala-L-Chp)-OH 在 碳酸氢钠 、 3-(二乙氧基邻酰氧基)-1,2,3-苯并三嗪-4-酮 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 以119 mg的产率得到Fmoc-Asn(Trt)-Dap(Boc-Leu-D-Ala-Chp)-D-Hpg-D-Orn(SES)-D-aThr-Hpg-D-Hpg-aThr-Phe-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：

  Fmoc-L-Dap(Boc-L-Leu-D-Ala-L-Chp)-OBn 在 palladium on activated charcoal N-羟基-7-氮杂苯并三氮唑 、 四丁基氟化铵 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 49.17h， 生成 Fmoc-L-Asn(Trt)-L-Dap(Boc-L-Leu-D-Ala-L-Chp)-OH
  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

文献信息

• 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。