tert-butyl (S)-4-(((2S,3R)-1-((2-(allyloxy)-2-oxoethyl)amino)-3-hydroxy-1-oxobutan-2-yl)amino)-3-azido-4-oxobutanoate | 1429504-41-5

• 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: tert-butyl (S)-4-(((2S,3R)-1-((2-(allyloxy)-2-oxoethyl)amino)-3-hydroxy-1-oxobutan-2-yl)amino)-3-azido-4-oxobutanoate
• 英文别名: tert-butyl (3S)-3-azido-4-[[(2S,3R)-3-hydroxy-1-oxo-1-[(2-oxo-2-prop-2-enoxyethyl)amino]butan-2-yl]amino]-4-oxobutanoate
• CAS: 1429504-41-5
• 化学式: C₁₇H₂₇N₅O₇
• 分子量: 413.431
• InChiKey: XYUKYPQKZSNGSH-SUNKGSAMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  29
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  145
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-4-(((2S,3R)-1-((2-(allyloxy)-2-oxoethyl)amino)-3-hydroxy-1-oxobutan-2-yl)amino)-3-azido-4-oxobutanoate 在 四(三苯基膦)钯 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 臭氧 、 N,N-二异丙基乙胺 、 N-甲基苯胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 18.08h， 生成 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：

  在 四丁基氟化铵 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以1.3 g的产率得到tert-butyl (S)-4-(((2S,3R)-1-((2-(allyloxy)-2-oxoethyl)amino)-3-hydroxy-1-oxobutan-2-yl)amino)-3-azido-4-oxobutanoate
  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。
• Methylation of Daptomycin Leading to the Discovery of Kynomycin, a Cyclic Lipodepsipeptide Active against Resistant Pathogens
  作者：Hoi Yee Chow、Kathy Hiu Laam Po、Peng Gao、Pilar Blasco、Xiukun Wang、Congran Li、Lianwei Ye、Kang Jin、Kaichao Chen、Edward Wai Chi Chan、Xuefu You、Richard Yi Tsun Kao、Sheng Chen、Xuechen Li

  DOI：10.1021/acs.jmedchem.9b01957

  日期：2020.3.26

  Increased usage of daptomycin to treat infections caused by Gram-positive bacterial pathogens has resulted in emergence of resistant mutants. In a search for more effective daptomycin analogues through medicinal chemistry studies, we found that methylation at the nonproteinogenic amino acid kynurenine in daptomycin could result in significant enhancement of antibacterial activity. Termed "kynomycin," this new antibiotic exhibits higher antibacterial activity than daptomycin and is able to eradicate methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) strains, including dapto-mycin-resistant strains. The improved antimicrobial activity of kynomycin was demonstrated in in vitro time-killing assay, in vivo wax worm model, and different mouse infection models. The increased antibacterial activity, improved pharmacokinetics, and lower cytotoxicity of kynomycin, compared to daptomycin, showed the promise of the future design and development of next-generation daptomycin-based antibiotics.
• Total Synthesis of Daptomycin by Cyclization via a Chemoselective Serine Ligation
  作者：Hiu Yung Lam、Yinfeng Zhang、Han Liu、Jianchao Xu、Clarence T. T. Wong、Ci Xu、Xuechen Li

  DOI：10.1021/ja4012468

  日期：2013.4.24

  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.