tert-butyl 4-(acetylthio)-3(S)-(tert-butoxycarbonylamino)butanoate | 220542-07-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: tert-butyl 4-(acetylthio)-3(S)-(tert-butoxycarbonylamino)butanoate
• 英文别名: tert-butyl (3S)-4-acetylsulfanyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate
• CAS: 220542-07-4
• 化学式: C₁₅H₂₇NO₅S
• 分子量: 333.449
• InChiKey: VKXFMIFPBNRRRO-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(acetylthio)-3(S)-(tert-butoxycarbonylamino)butanoate 在 sodium methylate 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 2.58h， 生成 (1-tert-butyldisulfanylmethyl-5,5-dimethyl-3-oxo-hexyl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  合成非蛋白氨基酸来探索羊毛硫抗生素的生物合成

  摘要：

  描述了六种经过适当保护的非蛋白氨基酸的合成，用于基于 Fmoc 的固相肽合成。这些氨基酸是( 2S , 3R )-乙烯基苏氨酸、( 2S )-( E )-2-氨基-5-氟-戊-3-烯酸(氟烯丙基甘氨酸)、( S ) -β2-高丝氨酸、 ( S)和( R )-β 3-同型半胱氨酸，和( 2R , 3R )-甲基半胱氨酸。一旦掺入肽中，这些化合物有望作为羊毛硫抗生素合酶的替代底物，羊毛硫抗生素合酶使肽底物中的丝氨酸和苏氨酸残基脱水，并催化随后半胱氨酸与脱氢氨基酸的分子内迈克尔型加成。

  DOI：

  10.1021/jo051182o
• 作为产物：
  描述：

  BOC-L-天门冬氨酸4-叔丁基-1-羟基-琥珀酰亚胺酯 在 吡啶 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 tert-butyl 4-(acetylthio)-3(S)-(tert-butoxycarbonylamino)butanoate
  参考文献：
  名称：

  Desazadesmethyldesferrithiocin Analogues as Orally Effective Iron Chelators

  摘要：

  Further structure-activity studies of desferrithiocin analogues are carried out. (S)-desazadesmethyldesferrithiocin, 2-(2-hydroxyphenyl)-Delta(2)-thiazoline-4(S)-carboxylic acid, serves as the principal framework in the current paper. Desazadesmethyldesferrithiocin can be structurally altered with facility, and data are already available on its iron-clearing properties and toxicity parameters. Four different kinds of structural modifications of this framework are undertaken: introduction of hydroxy, carboxy, or methoxy groups on the aromatic ring; alteration of the thiazoline ring; increasing the distance between the ligand donor atoms; and benz-fusion of the aromatic rings. The structural modifications described are shown to have a tremendous imp act on both the iron clearance and toxicity profiles of the desazadesmethyldesferrithiocin molecule. All of the compounds are assessed in a bile-duct-cannulated rodent model to determine iron clearance efficiency. Ligands which demonstrate an efficiency of greater than 2% are carried forward to the iron-overloaded primate for iron-clearing measurements. Ligands with efficiencies greater than 3% in the primate are then evaluated in a formal toxicity study in rodents. On the basis of the results of the present work, 2-(2,4-dihydroxyphenyl)-Delta(2)-thiazoline-4(S)-carboxylic acid is a promising candidate for clinical evaluation.

  DOI：

  10.1021/jm980340j

文献信息

• Desazadesmethyldesferrithiocin Analogues as Orally Effective Iron Chelators
  作者：Raymond J. Bergeron、Jan Wiegand、William R. Weimar、J. R. Timothy Vinson、Jörg Bussenius、Guo Wei Yao、James S. McManis

  DOI：10.1021/jm980340j

  日期：1999.1.1

  Further structure-activity studies of desferrithiocin analogues are carried out. (S)-desazadesmethyldesferrithiocin, 2-(2-hydroxyphenyl)-Delta(2)-thiazoline-4(S)-carboxylic acid, serves as the principal framework in the current paper. Desazadesmethyldesferrithiocin can be structurally altered with facility, and data are already available on its iron-clearing properties and toxicity parameters. Four different kinds of structural modifications of this framework are undertaken: introduction of hydroxy, carboxy, or methoxy groups on the aromatic ring; alteration of the thiazoline ring; increasing the distance between the ligand donor atoms; and benz-fusion of the aromatic rings. The structural modifications described are shown to have a tremendous imp act on both the iron clearance and toxicity profiles of the desazadesmethyldesferrithiocin molecule. All of the compounds are assessed in a bile-duct-cannulated rodent model to determine iron clearance efficiency. Ligands which demonstrate an efficiency of greater than 2% are carried forward to the iron-overloaded primate for iron-clearing measurements. Ligands with efficiencies greater than 3% in the primate are then evaluated in a formal toxicity study in rodents. On the basis of the results of the present work, 2-(2,4-dihydroxyphenyl)-Delta(2)-thiazoline-4(S)-carboxylic acid is a promising candidate for clinical evaluation.
• Synthesis of Nonproteinogenic Amino Acids To Probe Lantibiotic Biosynthesis
  作者：Xingang Zhang、Weijuan Ni、Wilfred A. van der Donk

  DOI：10.1021/jo051182o

  日期：2005.8.1

  The synthesis of six nonproteinogenic amino acids appropriately protected for Fmoc-based solid-phase peptide synthesis is described. These amino acids are (2S,3R)-vinylthreonine, (2S)-(E)-2-amino-5-fluoro-pent-3-enoic acid (fluoroallylglycine), (S)-β2-homoserine, (S) and (R)-β3-homocysteine, and (2R,3R)-methylcysteine. Once incorporated into peptides, these compounds were envisioned to serve as alternative

  描述了六种经过适当保护的非蛋白氨基酸的合成，用于基于 Fmoc 的固相肽合成。这些氨基酸是( 2S , 3R )-乙烯基苏氨酸、( 2S )-( E )-2-氨基-5-氟-戊-3-烯酸(氟烯丙基甘氨酸)、( S ) -β2-高丝氨酸、 ( S)和( R )-β 3-同型半胱氨酸，和( 2R , 3R )-甲基半胱氨酸。一旦掺入肽中，这些化合物有望作为羊毛硫抗生素合酶的替代底物，羊毛硫抗生素合酶使肽底物中的丝氨酸和苏氨酸残基脱水，并催化随后半胱氨酸与脱氢氨基酸的分子内迈克尔型加成。