2-(S)-Azido-3-(R)-hydroxybutanoic acid | 294659-97-5

• 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: 2-(S)-Azido-3-(R)-hydroxybutanoic acid
• 英文别名: N3^α-Thr-OH；(2S,3R)-2-azido-3-hydroxybutanoic acid
• CAS: 294659-97-5
• 化学式: C₄H₇N₃O₃
• 分子量: 145.118
• InChiKey: CJRVQJULIIGUDT-GBXIJSLDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  71.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(S)-Azido-3-(R)-hydroxybutanoic acid 、 N-Boc-哌嗪 在 N-甲基吗啉 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 14.0h， 生成 C₁₃H₂₃N₅O₄
  参考文献：
  名称：

  A Combinatorial Method for Solution-Phase Synthesis of Labeled Bivalent β-Turn Mimics

  摘要：

  Piperidine-functionalized, 1,4-disubstituted-1,2,3-triazoles of generic structure 1 were conceived as "minimalist" mimics of peptidic beta-turn structures. Key features of these molecules include (i) the possibility of incorporating amino acid side chains corresponding to many of the protein amino acids; (ii) a close correspondence of separations of these side chains to i + 1 to i + 2 residues in turns; (iii) facile adjustment of the side-chain vectors on docking while only influencing two critical degrees of freedom; and (iv) some electrostatic polarity. Fifteen monomers of this type were made via copper-mediated cycloaddition reactions. Solution-phase methodologies were devised to assemble these monomers into bivalent compounds in high purity states (typically >85%) so that they could be used in first-pass biological assays without further purification. The skeleton for forming these bivalent compounds is triazine-based. There is a third site which allowed for introduction of a fluorescent label (library of compounds 2) or an alkyne-functionalized triethylene glycol chain (library of compounds 3) included to promote water-solubility and to allow incorporation of probes via copper-mediated cycloaddition reactions. In the event, two 135-membered libraries were prepared, one consisting of compounds 2 and the other of 3. No protecting groups or coupling agents were required; these attributes of the method were important to allow most of the products to be obtained in over 85% purities. The fluorescein-tagged library of compounds 2 was screened in a fluorescence-activated cell sorting (FACS) assay using cells transfected to overexpress one of the following neurotrophin receptors: TrkA, TrkC, and p75. Preliminary findings indicate four compounds 2gm, 2gn, 2gi, and 2gj bound the TrkA receptor selectively; all of these contain a threonine-lysine turn mimic. Thus, a pharmacological probe for the TrkA receptor has been developed.

  DOI：

  10.1021/ja074717z
• 作为产物：
  描述：

  L-苏氨酸 在 copper(II) sulfate triflic azide 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 14.0h， 生成 2-(S)-Azido-3-(R)-hydroxybutanoic acid
  参考文献：
  名称：

  A Combinatorial Method for Solution-Phase Synthesis of Labeled Bivalent β-Turn Mimics

  摘要：

  Piperidine-functionalized, 1,4-disubstituted-1,2,3-triazoles of generic structure 1 were conceived as "minimalist" mimics of peptidic beta-turn structures. Key features of these molecules include (i) the possibility of incorporating amino acid side chains corresponding to many of the protein amino acids; (ii) a close correspondence of separations of these side chains to i + 1 to i + 2 residues in turns; (iii) facile adjustment of the side-chain vectors on docking while only influencing two critical degrees of freedom; and (iv) some electrostatic polarity. Fifteen monomers of this type were made via copper-mediated cycloaddition reactions. Solution-phase methodologies were devised to assemble these monomers into bivalent compounds in high purity states (typically >85%) so that they could be used in first-pass biological assays without further purification. The skeleton for forming these bivalent compounds is triazine-based. There is a third site which allowed for introduction of a fluorescent label (library of compounds 2) or an alkyne-functionalized triethylene glycol chain (library of compounds 3) included to promote water-solubility and to allow incorporation of probes via copper-mediated cycloaddition reactions. In the event, two 135-membered libraries were prepared, one consisting of compounds 2 and the other of 3. No protecting groups or coupling agents were required; these attributes of the method were important to allow most of the products to be obtained in over 85% purities. The fluorescein-tagged library of compounds 2 was screened in a fluorescence-activated cell sorting (FACS) assay using cells transfected to overexpress one of the following neurotrophin receptors: TrkA, TrkC, and p75. Preliminary findings indicate four compounds 2gm, 2gn, 2gi, and 2gj bound the TrkA receptor selectively; all of these contain a threonine-lysine turn mimic. Thus, a pharmacological probe for the TrkA receptor has been developed.

  DOI：

  10.1021/ja074717z

文献信息

• Synthesis and application of sialic acid-containing building blocks for glycopeptide libraries. Establishing glycosylation conditions
  作者：Koen M. Halkes、Phaedria M. St. Hilaire、Anita M. Jansson、Charlotte H. Gotfredsen、Morten Meldal

  DOI：10.1039/a908321i

  日期：——

  Three different sialic acid-containing building blocks (6–8) were synthesized for use in solid-phase glycopeptide libraries. Investigation of the conditions for glycosylation of threonine (Thr) with various sialic acid donors revealed that the best results were obtained by coupling glycosyl xanthate 2 to the acceptors Fmoc-Thr-OH (5) or the α-azido acid analogue of Thr, 4. Among several catalysts employed, phenylsulfanyl triflate (PST) afforded the best yields. Both the N-Fmoc and α-azido analogues of Thr allowed glycosylation with good stereoselectivity in 80% (→ 8) and 84% (→ 6) yield, respectively. Introduction of a phenylthio group in the 3 position of the sialic acid donor 3, to assist the stereoselective outcome of the glycosylation reaction, gave good results; however difficulties in the removal of the phenylthio auxiliary group made this route less attractive. Both building blocks 6 and 8 were successfully introduced in solid-phase glycopeptide synthesis. Interestingly, alkaline deprotection of the Fmoc group of 8, necessary for subsequent introduction of amino acids, resulted in an immediate attack of the α-amino group on the sialic acid methyl ester to form the lactam 14. This side reaction was also observed during reduction of the azido acid building block 6 under alkaline conditions, but could be suppressed by performing the reduction under acidic conditions. Lactam formation was completely avoided by hydrolysis of the methyl ester prior to reduction of the azide.

  合成了三种不同的含唾液酸结构单元 (6-8)，用于固相糖肽文库。对苏氨酸 (Thr) 与各种唾液酸供体的糖基化条件的研究表明，通过将糖基黄原酸 2 与受体 Fmoc-Thr-OH (5) 或 Thr, 4 的 α-叠氮酸类似物偶联可获得最佳结果在使用的几种催化剂中，苯硫基三氟甲磺酸酯（PST）的产率最高。 Thr 的 N-Fmoc 和 α-叠氮类似物都可以进行糖基化，具有良好的立体选择性，产率分别为 80% (→ 8) 和 84% (→ 6)。在唾液酸供体3的3位引入苯硫基，以辅助糖基化反应的立体选择性结果，得到了良好的结果；然而，去除苯硫基辅助基团的困难使得该路线不太有吸引力。 结构单元 6 和 8 均已成功引入固相糖肽合成中。有趣的是，随后引入氨基酸所必需的 Fmoc 基团 8 的碱性脱保护导致 α-氨基立即攻击唾液酸甲酯，形成内酰胺 14。在还原过程中也观察到了这种副反应叠氮酸结构单元6在碱性条件下的还原，但可以通过在酸性条件下进行还原来抑制。通过在叠氮化物还原之前水解甲酯，完全避免了内酰胺的形成。
• A Combinatorial Method for Solution-Phase Synthesis of Labeled Bivalent β-Turn Mimics
  作者：Yu Angell、Dianjun Chen、Fouad Brahimi、H. Uri Saragovi、Kevin Burgess

  DOI：10.1021/ja074717z

  日期：2008.1.1

  Piperidine-functionalized, 1,4-disubstituted-1,2,3-triazoles of generic structure 1 were conceived as "minimalist" mimics of peptidic beta-turn structures. Key features of these molecules include (i) the possibility of incorporating amino acid side chains corresponding to many of the protein amino acids; (ii) a close correspondence of separations of these side chains to i + 1 to i + 2 residues in turns; (iii) facile adjustment of the side-chain vectors on docking while only influencing two critical degrees of freedom; and (iv) some electrostatic polarity. Fifteen monomers of this type were made via copper-mediated cycloaddition reactions. Solution-phase methodologies were devised to assemble these monomers into bivalent compounds in high purity states (typically >85%) so that they could be used in first-pass biological assays without further purification. The skeleton for forming these bivalent compounds is triazine-based. There is a third site which allowed for introduction of a fluorescent label (library of compounds 2) or an alkyne-functionalized triethylene glycol chain (library of compounds 3) included to promote water-solubility and to allow incorporation of probes via copper-mediated cycloaddition reactions. In the event, two 135-membered libraries were prepared, one consisting of compounds 2 and the other of 3. No protecting groups or coupling agents were required; these attributes of the method were important to allow most of the products to be obtained in over 85% purities. The fluorescein-tagged library of compounds 2 was screened in a fluorescence-activated cell sorting (FACS) assay using cells transfected to overexpress one of the following neurotrophin receptors: TrkA, TrkC, and p75. Preliminary findings indicate four compounds 2gm, 2gn, 2gi, and 2gj bound the TrkA receptor selectively; all of these contain a threonine-lysine turn mimic. Thus, a pharmacological probe for the TrkA receptor has been developed.