(S)-2-hydroxy-4-azidobutyric acid | 959148-55-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (S)-2-hydroxy-4-azidobutyric acid
• 英文别名: AHB；(2S)-N3-Haba；(2S)-4-azido-2-hydroxybutanoic acid
• CAS: 959148-55-1
• 化学式: C₄H₇N₃O₃
• 分子量: 145.118
• InChiKey: UERAIPHBLAAUFG-VKHMYHEASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  10
• 可旋转键数：
  4
• 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：

  (S)-2-hydroxy-4-azidobutyric acid 、 2',3-diazido-1-N-[(tert-butoxy)carbonyl]paromamine 在 三氟乙酸 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 甲胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙醇 为溶剂， 反应 12.0h， 以93%的产率得到2',3-diazido-1-N-[(S)-4-azido-2-hydroxy-butanoyl]paromamine
  参考文献：
  名称：

  Novel aminoglycosides and uses thereof in the treatment of genetic disorders

  摘要：

  提供了一类新型的巴罗霉素衍生氨基糖苷类化合物，具有高效的终止密码子突变抑制活性、低毒性和高选择性作用于真核细胞。同时提供了制备这些巴罗霉素衍生氨基糖苷类化合物及其中间体的化学和化酶过程，以及含有它们的药物组合物，并在遗传疾病治疗中的应用。

  公开号：

  US20090093418A1
• 作为产物：
  描述：

  (S)-4-amino-2-hydroxybutanoic acid 在 triflic azide 、 copper(II) sulfate 、 三乙胺 作用下， 反应 8.0h， 以90%的产率得到(S)-2-hydroxy-4-azidobutyric acid
  参考文献：
  名称：

  氨基糖苷衍生物与N-1-AHB侧链的化学-酶结合组装

  摘要：

  通过使用重组体，在有价值的（S）-4-氨基-2-羟基丁酰基（AHB）药效基团的N-1位选择性地酰化了一系列含2-脱氧链胺胺的氨基糖苷的一系列未保护的伪二糖和伪三糖。Butirosin生物合成中的BtrH和BtrG酶与合成的酰基供体结合。通过在不纯化中间产物的情况下依次进行两个酶促步骤来优化工艺。

  DOI：

  10.1002/adsc.200800229

文献信息

• Combined Chemical-Enzymatic Assembly of Aminoglycoside Derivatives with N-1-AHB Side Chain
  作者：Igor Nudelman、Lilach Chen、Nicholas M. Llewellyn、El-Habib Sahraoui、Marina Cherniavsky、Jonathan B. Spencer、Timor Baasov

  DOI：10.1002/adsc.200800229

  日期：2008.8.4

  A series of unprotected pseudo-disaccharides and pseudo-trisaccharides of 2-deoxystreptamine-containing aminoglycosides have been selectively acylated at the N-1 position with the valuable (S)-4-amino-2-hydroxybutanoyl (AHB) pharmacophore by using the recombinant BtrH and BtrG enzymes from butirosin biosynthesis in combination with a synthetic acyl donor. The process was optimized by performing two

  通过使用重组体，在有价值的（S）-4-氨基-2-羟基丁酰基（AHB）药效基团的N-1位选择性地酰化了一系列含2-脱氧链胺胺的氨基糖苷的一系列未保护的伪二糖和伪三糖。Butirosin生物合成中的BtrH和BtrG酶与合成的酰基供体结合。通过在不纯化中间产物的情况下依次进行两个酶促步骤来优化工艺。
• Development of Novel Aminoglycoside (NB54) with Reduced Toxicity and Enhanced Suppression of Disease-Causing Premature Stop Mutations
  作者：Igor Nudelman、Annie Rebibo-Sabbah、Marina Cherniavsky、Valery Belakhov、Mariana Hainrichson、Fuquan Chen、Jochen Schacht、Daniel S. Pilch、Tamar Ben-Yosef、Timor Baasov

  DOI：10.1021/jm801640k

  日期：2009.5.14

  Nonsense mutations promote premature translational termination and represent the underlying cause of a large number of human genetic diseases. The aminoglycoside antibiotic gentamicin has the ability to allow the mammalian ribosome to read past a false-stop signal and generate full-length functional proteins. However; severe toxic side effects along with the reduced suppression efficiency at subtoxic doses limit the use of gentamicin for suppression therapy. We describe here the first systematic development of the novel aminoglycoside 2 (NB54) exhibiting superior in vitro readthrough efficiency to that of gentamicin in seven different DNA fragments derived from mutant genes carrying nonsense mutations representing the genetic diseases Usher syndrome, cystic fibrosis, Duchenne muscular dystrophy, and Hurler syndrome. Comparative acute lethal toxicity in mice, cell toxicity, and the assessment of hair cell toxicity in cochlear explants further indicated that 2 exhibits far lower toxicity than that of gentamicin.
• Repairing faulty genes by aminoglycosides: Development of new derivatives of geneticin (G418) with enhanced suppression of diseases-causing nonsense mutations
  作者：Igor Nudelman、Dana Glikin、Boris Smolkin、Mariana Hainrichson、Valery Belakhov、Timor Baasov

  DOI：10.1016/j.bmc.2010.03.060

  日期：2010.6.1

  New pseudo-di- and pseudo-trisaccharide derivatives of the aminoglycoside drug G418 were designed, synthesized and their ability to readthrough nonsense mutations was examined in both in vitro and ex vivo systems, along with the toxicity tests. Two novel lead structures, NB74 and NB84, exhibiting significantly reduced cell toxicity and superior readthrough efficiency than those of gentamicin, were discovered. The superiority of new leads was demonstrated in six different nonsense DNA-constructs underling the genetic diseases cystic fibrosis, Duchenne muscular dystrophy, Usher syndrome and Hurler syndrome. (C) 2010 Elsevier Ltd. All rights reserved.
• Rigid spiroethers targeting the decoding center of the bacterial ribosome
  作者：Ioannis Mavridis、Georgia Kythreoti、Konstantina Koltsida、Dionisios Vourloumis

  DOI：10.1016/j.bmc.2013.12.068

  日期：2014.2

  Continuing our efforts towards understanding the principles governing ribosomal recognition and function, we have synthesized and evaluated a series of diversely functionalized 5,6-, 6,6- and 7,6- spiroethers. These compounds successfully mimic natural aminoglycosides regarding their binding to the decoding center of the bacterial ribosome. Their potential to inhibit prokaryotic protein production in vitro along with their antibacterial potencies have also been examined. (C) 2014 Elsevier Ltd. All rights reserved.
• Novel aminoglycosides and uses thereof in the treatment of genetic disorders
  申请人：Bassov Timor

  公开号：US20090093418A1

  公开（公告）日：2009-04-09

  A new class of paromomycin-derived aminoglycosides, which exhibit efficient stop-codon mutation suppression activity, low toxicity and high selectivity towards eukaryotic cells are provided. Also provided are chemical and chemo-enzymatic processes of preparing these paromomycin-derived aminoglycosides and intermediates thereof, as well as pharmaceutical compositions containing the same, and uses thereof in the treatment of genetic disorders.

  提供了一类新型的巴罗霉素衍生氨基糖苷类化合物，具有高效的终止密码子突变抑制活性、低毒性和高选择性作用于真核细胞。同时提供了制备这些巴罗霉素衍生氨基糖苷类化合物及其中间体的化学和化酶过程，以及含有它们的药物组合物，并在遗传疾病治疗中的应用。