3-(N-乙酰基-N-羟基)氨基丙基膦酸 | 66508-32-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 中文名称: 3-(N-乙酰基-N-羟基)氨基丙基膦酸
• 英文名称: 3-(N-acetyl-N-hydroxyamino)propylphosphonic acid
• 英文别名: FR 900098；{3-[acetyl(benzyloxy)amino]propyl}phosphonic acid；3-(acetylhydroxyamino)propylphosphonic acid；FR-900098；FR900098；FR‐900098；(3-(Acetylhydroxyamino)propyl)phosphonic acid；3-[acetyl(hydroxy)amino]propylphosphonic acid
• CAS: 66508-32-5
• 化学式: C₅H₁₂NO₅P
• mdl: MFCD01939854
• 分子量: 197.128
• InChiKey: PKMNDDZSIHLLLI-UHFFFAOYSA-N

物化性质

• 沸点：
  448.9±55.0 °C(Predicted)
• 密度：
  1.492±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.2
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  98.1
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 海关编码：
  2931900090

反应信息

• 作为反应物：
  描述：

  3-(N-乙酰基-N-羟基)氨基丙基膦酸 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 {3-[acetyl(benzyloxy)amino]propyl}phosphonic acid disodium salt
  参考文献：
  名称：

  抗疟药 FR900098 及其衍生物的新型短而有效的合成途径

  摘要：

  我们在此报告了一种新的操作简单、经济且环保的多组分方法，用于一锅法合成抗疟剂 FR900098。该反应允许从简单和市售的底物和试剂快速构建化合物，也适用于合成 FR900098 的修饰衍生物。

  DOI：

  10.1055/s-2007-990811
• 作为产物：
  描述：

  diethyl [3-(N-acetyl-N-hydroxyamino)-propyl]-phosphonate 在 三甲基溴硅烷 、 水 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以90%的产率得到3-(N-乙酰基-N-羟基)氨基丙基膦酸
  参考文献：
  名称：

  Synthesis of the Antimalarial Drug FR900098 Utilizing the Nitroso-Ene Reaction

  摘要：

  The antimalarial drug FR900098 was prepared from diethyl allylphosphonate involving the nitroso-ene reaction with nitrosocarbonyl methane as the key step followed by hydrogenation and dealkylation. The utilization of dibenzyl allylphosphonate as the starting compound allows one-step hydrogenation with dealkylation, which simplifies the preparative scheme further.

  DOI：

  10.1021/ol702082k

文献信息

• Studies on phosphonic acid antibiotics. I. Structure and synthesis of 3-(n-acetyl-n-hydroxyamino)propylphosphonic acid (FR-900098) and its n-formyl analogue (FR-31564)
  作者：Takashi Kamiya、Keiji Hemmi、Hidekazu Takeno、Masashi Hashimoto

  DOI：10.1016/s0040-4039(00)93633-5

  日期：1980.1

  The structure elucidation of FR-900098 (1) isolated from a microorganism source and the syntheses of FR-900098 and its N-formyl analogue, FR-31564 (2), are described. The latter possesses a superior antimicrobial activity.

  描述了从微生物来源分离的FR-900098（1）的结构以及FR-900098及其N-甲酰基类似物FR-31564（2）的合成。后者具有优异的抗菌活性。
• Characterization and application of the Fe(ii) and α-ketoglutarate dependent hydroxylase FrbJ
  作者：Matthew A. DeSieno、Wilfred A. van der Donk、Huimin Zhao

  DOI：10.1039/c1cc13597j

  日期：——

  The Fe(II) and α-ketoglutarate-dependent hydroxylase FrbJ was previously demonstrated to utilize FR-900098 synthesizing a second phosphonate FR-33289. Here we assessed its ability to hydroxylate other possible substrates, generating a library of potential antimalarial compounds. Through a series of bioassays and in vitro experiments, we identified two new antimalarials.

  Fe(II)和α-酮戊二酸依赖的羟化酶FrbJ之前已被证实能够利用FR-900098合成第二种磷酸酯FR-33289。在这里，我们评估了它对其他可能底物的羟化能力，生成了一系列潜在的抗疟药物。在一系列生物测定和体外实验中，我们发现了两种新的抗疟药物。
• Studies on phosphonic acid antibiotics. III. Structure and synthesis of 3-(N-acetyl-N-hydroxyamino)propylphosphonic acid (FR-900098) and 3-(N-acetyl-N-hydroxyamino)-2(R)-hydroxypropylphosphonic acid (FR-33289)
  作者：KEIJI HEMMI、HIDEKAZU TAKENO、MASASHI HASHIMOTO、TAKASHI KAMIYA

  DOI：10.1248/cpb.29.646

  日期：——

  The structures of the antibiotics FR-900098 (II) and FR-33289 (III), isolated from Streptomyces rubellomurius, have been established as 3-(N-acetyl-N-hydroxyamino)-propylphosphonic acid and 3-(N-acetyl-N-hydroxyamino)-2 (R)-hydroxypropylphosphonic acid, respectively, on the basis of spectroscopic and chemical evidence and, finally, by synthesis.

  从红斑链霉菌中分离出来的抗生素 FR-900098 (II) 和 FR-33289 (III) 的结构已确定为 3-(N-乙酰基-N-羟氨基)-丙基膦酸和 3-(N-乙酰基- N-羟基氨基)-2(R)-羟丙基膦酸，分别基于光谱和化学证据，最后通过合成。
• DE2733658
  申请人：——

  公开号：——

  公开（公告）日：——
• Deciphering the Late Biosynthetic Steps of Antimalarial Compound FR-900098
  作者：Tyler W. Johannes、Matthew A. DeSieno、Benjamin M. Griffin、Paul M. Thomas、Neil L. Kelleher、William W. Metcalf、Huimin Zhao

  DOI：10.1016/j.chembiol.2009.12.009

  日期：2010.1

  FR-900098 is a potent chemotherapeutic agent for the treatment of malaria. Here we report the heterologous production of this compound in Escherichia coli by reconstructing the entire biosynthetic pathway using a three-plasmid system. Based on this system, whole-cell feeding assays in combination with in vitro enzymatic activity assays reveal an unusual functional role of nucleotide conjugation and lead to the complete elucidation of the previously unassigned late biosynthetic steps. These studies also suggest a biosynthetic route to a second phosphonate antibiotic, FR-33289. A thorough understanding of the FR-900098 biosynthetic pathway now opens possibilities for metabolic: engineering in E. coli to increase production of the antimalarial antibiotic and combinatorial biosynthesis to generate novel derivatives of FR-900098.