2-[[(2S,3R)-2-[[(2S)-2-azido-4-[(2-methylpropan-2-yl)oxy]-4-oxobutanoyl]amino]-3-[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[1-[(2-methylpropan-2-yl)oxycarbonyl]indol-3-yl]propanoyl]oxybutanoyl]amino]acetic acid | 1429504-43-7

• 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: 2-[[(2S,3R)-2-[[(2S)-2-azido-4-[(2-methylpropan-2-yl)oxy]-4-oxobutanoyl]amino]-3-[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[1-[(2-methylpropan-2-yl)oxycarbonyl]indol-3-yl]propanoyl]oxybutanoyl]amino]acetic acid
• CAS: 1429504-43-7
• 化学式: C₄₅H₅₁N₇O₁₂
• 分子量: 881.94
• InChiKey: YUNKAYLIQVAXRO-MHNPHYDPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  64
• 可旋转键数：
  22
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  232
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  2-[[(2S,3R)-2-[[(2S)-2-azido-4-[(2-methylpropan-2-yl)oxy]-4-oxobutanoyl]amino]-3-[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[1-[(2-methylpropan-2-yl)oxycarbonyl]indol-3-yl]propanoyl]oxybutanoyl]amino]acetic acid 在 臭氧 、 二甲基硫 作用下， 以 二氯甲烷 为溶剂， 反应 2.08h， 以95%的产率得到O-((S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(2-(N-(tert-butoxycarbonyl)formamido)phenyl)-4-oxobutanoyl)-N-((S)-2-azido-4-(tert-butoxy)-4-oxobutanoyl)-L-threonylglycine
  参考文献：
  名称：

  Total Synthesis of Daptomycin by Cyclization via a Chemoselective Serine Ligation

  摘要：

  A total synthesis of daptomycin, the first natural product antibiotic launched in a generation, was achieved. This convergent synthesis relies on an efficient macrocyclization via a serine ligation to assemble the 31-membered cyclic depsipeptide. The difficult esterification by the nonproteinogenic amino acid kynurenine was accomplished via the esterification of a threonine residue by a suitably protected Trp ester, followed by ozonolysis. This synthesis provides a foundation and framework to prepare varied analogues of daptomycin to establish its structure-activity profile.

  DOI：

  10.1021/ja4012468
• 作为产物：
  描述：

  Fmoc-L-天冬氨酸 beta-叔丁酯 在 1H-咪唑-1-磺酰叠氮盐酸盐 、 四(三苯基膦)钯 、 copper(ll) sulfate pentahydrate 、 四丁基氟化铵 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 碳酸氢钠 、 溶剂黄146 、 二乙胺 、 N,N-二异丙基乙胺 、 N-甲基苯胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 42.0h， 生成 2-[[(2S,3R)-2-[[(2S)-2-azido-4-[(2-methylpropan-2-yl)oxy]-4-oxobutanoyl]amino]-3-[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[1-[(2-methylpropan-2-yl)oxycarbonyl]indol-3-yl]propanoyl]oxybutanoyl]amino]acetic acid
  参考文献：
  名称：

  Total Synthesis of Daptomycin by Cyclization via a Chemoselective Serine Ligation

  摘要：

  A total synthesis of daptomycin, the first natural product antibiotic launched in a generation, was achieved. This convergent synthesis relies on an efficient macrocyclization via a serine ligation to assemble the 31-membered cyclic depsipeptide. The difficult esterification by the nonproteinogenic amino acid kynurenine was accomplished via the esterification of a threonine residue by a suitably protected Trp ester, followed by ozonolysis. This synthesis provides a foundation and framework to prepare varied analogues of daptomycin to establish its structure-activity profile.

  DOI：

  10.1021/ja4012468

文献信息

• DAPTOMYCIN ANALOGUES AND A METHOD FOR THE PREPARATION OF DAPTOMYCIN OR A DAPTOMYCIN ANALOGUE
  申请人：THE UNIVERSITY OF HONG KONG

  公开号：US20150126707A1

  公开（公告）日：2015-05-07

  A method for the synthesis of daptomycin or a daptomycin analogue is carried out on a resin to form a linear precursor followed by a serine ligation macrocyclization in solution. Daptomycin analogues can differ from daptomycin by substitution of amino acids residues and/or deletion or addition of amino acid residues. Daptomycin analogues can include a different fatty acid in the side arm of the daptomycin analogue.

  一种合成达托霉素或达托霉素类似物的方法在树脂上进行，形成线性前体，然后在溶液中进行丝氨酸连接的大环化反应。达托霉素类似物可以通过替换氨基酸残基和/或删除或添加氨基酸残基与达托霉素不同。达托霉素类似物的侧链中可以包含不同的脂肪酸。