(R,S)-(2-Hydroxypropyl)phosphonsaeure | 76274-77-6

• 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
• 英文名称: (R,S)-(2-Hydroxypropyl)phosphonsaeure
• 英文别名: 2-hydroxypropylphosphonic acid；(2-hydroxy-propyl)-phosphonic acid；(2-Hydroxy-propyl)-phosphonsaeure
• CAS: 76274-77-6
• 化学式: C₃H₉O₄P
• 分子量: 140.076
• InChiKey: ZFVCONUOLQASEW-UHFFFAOYSA-N

物化性质

• 沸点：
  360.8±44.0 °C(Predicted)
• 密度：
  1.472±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  8
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R,S)-(2-Hydroxypropyl)phosphonsaeure 在 碳酸氢铵 作用下， 以 水 为溶剂， 生成
  参考文献：
  名称：

  Initial characterization of Fom3 from Streptomyces wedmorensis: The methyltransferase in fosfomycin biosynthesis

  摘要：

  Fosfomycin is a broad-spectrum antibiotic that is useful against multi-drug resistant bacteria. Although its biosynthesis was first studied over 40 years ago, characterization of the penultimate methyl transfer reaction has eluded investigators. The enzyme believed to catalyze this reaction, Fom3, has been identified as a radical S-adenosyl-L-methionine (SAM) superfamily member. Radical SAM enzymes use SAM and a four-iron, four-sulfur ([4Fe-4S]) cluster to catalyze complex chemical transformations. Fom3 also belongs to a family of radical SAM enzymes that contain a putative cobalamin-binding motif, suggesting that it uses cobalamin for methylation. Here we describe the first biochemical characterization of Fom3 from Streptomyces wedmorensis. Since recombinant Fom3 is insoluble, we developed a successful refolding and iron-sulfur cluster reconstitution procedure. Spectroscopic analyses demonstrate that Fom3 binds a [4Fe-4S] cluster which undergoes a transition between a +2 "resting" state and a +1 active state characteristic of radical SAM enzymes. Site-directed mutagenesis of the cysteine residues in the radical SAM CxxxCxxC motif indicates that each residue is essential for functional cluster formation. We also provide preliminary evidence that Fom3 adds a methyl group to 2-hydroxyethylphosphonate (2-HEP) to form 2-hydroxypropylphosphonate (2-HPP) in an apparently SAM-, sodium dithionite-, and methylcobalamin-dependent manner. (C) 2013 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.abb.2013.12.004
• 作为产物：
  描述：

  二甲基(2-羟丙基)膦酸酯 在 三甲基溴硅烷 、 烯丙基三甲基硅烷 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 (R,S)-(2-Hydroxypropyl)phosphonsaeure
  参考文献：
  名称：

  Initial characterization of Fom3 from Streptomyces wedmorensis: The methyltransferase in fosfomycin biosynthesis

  摘要：

  Fosfomycin is a broad-spectrum antibiotic that is useful against multi-drug resistant bacteria. Although its biosynthesis was first studied over 40 years ago, characterization of the penultimate methyl transfer reaction has eluded investigators. The enzyme believed to catalyze this reaction, Fom3, has been identified as a radical S-adenosyl-L-methionine (SAM) superfamily member. Radical SAM enzymes use SAM and a four-iron, four-sulfur ([4Fe-4S]) cluster to catalyze complex chemical transformations. Fom3 also belongs to a family of radical SAM enzymes that contain a putative cobalamin-binding motif, suggesting that it uses cobalamin for methylation. Here we describe the first biochemical characterization of Fom3 from Streptomyces wedmorensis. Since recombinant Fom3 is insoluble, we developed a successful refolding and iron-sulfur cluster reconstitution procedure. Spectroscopic analyses demonstrate that Fom3 binds a [4Fe-4S] cluster which undergoes a transition between a +2 "resting" state and a +1 active state characteristic of radical SAM enzymes. Site-directed mutagenesis of the cysteine residues in the radical SAM CxxxCxxC motif indicates that each residue is essential for functional cluster formation. We also provide preliminary evidence that Fom3 adds a methyl group to 2-hydroxyethylphosphonate (2-HEP) to form 2-hydroxypropylphosphonate (2-HPP) in an apparently SAM-, sodium dithionite-, and methylcobalamin-dependent manner. (C) 2013 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.abb.2013.12.004

文献信息

• Cloning and Expression in<i>Escherichia coli</i>of 2-Hydroxypropylphosphonic Acid Epoxidase from the Fosfomycin-producing Organism,<i>Pseudomonas syringae</i>PB-5123
  作者：Tomohisa KUZUYAMA、Takayuki SEKI、Seiji KOBAYASHI、Tomomi HIDAKA、Haruo SETO

  DOI：10.1271/bbb.63.2222

  日期：1999.1

  The fosfomycin resistance gene, fosC, has been cloned from the fosfomycin-producing organism, Pseudomonas syringae PB-5123. Sequence analysis upstream of this gene found a new ORF showing significant homology to 2-hydroxypropylphosphonic acid epoxidase from fosfomycin-producing Streptomyces wedmorensis. The purified recombinant protein of this ORF converted 2-hydroxypropylphosphonic acid to fosfomycin. This result clearly showed the ORF to encode 2-hydroxypropylphosphonic acid epoxidase in PB-5123.

  从产磷霉素的假单胞菌（Pseudomonas syringae PB-5123）中克隆出了磷霉素抗性基因 fosC。对该基因上游的序列分析发现了一个新的 ORF，它与产磷霉素的楔形链霉菌（Streptomyces wedmorensis）中的 2-hydroxypropylphosphonic acid epoxidase 有显著的同源性。该 ORF 的纯化重组蛋白可将 2-hydroxypropylphosphonic acid 转化为磷霉素。这一结果清楚地表明 ORF 编码 PB-5123 中的 2-hydroxypropylphosphonic acid epoxidase。
• Hydroxyaminohydrocarbonphosphonic acids
  申请人：Fujisawa Pharmaceutical Company, Limited

  公开号：US04206156A1

  公开（公告）日：1980-06-03

  New hydroxyaminohydrocarbonphosphonic acid derivatives of the formula: ##STR1## wherein R.sup.1 is hydrogen or acyl, R.sup.2 is hydrogen, lower alkyl, ar(lower)alkyl or acyl, and A is lower alkylene, lower alkenylene or hydroxy(lower)alkylene, or the esters at the phosphono group thereof or the pharmaceutical acceptable salt thereof, and production and use thereof.

  新的羟胺基羟基碳膦酸衍生物的化学式为：##STR1## 其中R.sup.1是氢或酰基，R.sup.2是氢、低级烷基、芳基(低级)烷基或酰基，A是低级烷基、低级烯基或羟基(低级)烷基，或其磷酸酯基或制药可接受的盐，以及其生产和使用。
• Markierte Vertreter eines m�glichen Zwischenprodukts der Biosynthese von Fosfomycin inStreptomyces fradiae: Darstellung von (R,S)-(2-Hydroxypropyl)-, (R,S)-, (R)-, (S)-(2-Hydroxy-[1,1-2H2]propyl)-und (R,S)-(2-[18O]Hydroxypropyl)phosphons�ure
  作者：Friedrich Hammerschmidt

  DOI：10.1007/bf00809660

  日期：1991.5

  Racemic methyl O-benzyllactate was reduced to the alcohol, transformed into the bromide and reacted with triethylphosphite to give the diethylphosphonate. Removal of protecting groups afforded a phosphonic acid which was purified as its cyclohexylammonium salt. (S)-Ethyl and (R)-isobutyl O-benzyllactate were reduced with LiAlD4 to the corresponding dideuteriated alcohols, which were transformed in the same way as the racemic compound into the chiral (2-hydroxy-[1,1-H-2(2)]propyl)phosphonic acids. The optical purity of alcohols (S)- and (R)-6b was determined by derivatisation with (+)-MTPA-Cl and H-1-NMR-spectroscopy to be 98%. Exchange of the carbonyl-16-oxygen atom of 2-oxopropylphosphonate for oxygen-18 from (H2O)-O-18, reduction with NaBH4, deprotection and addition of cyclohexylamine yielded the salt (+/-)-18 of (2-[O-18]hydroxy-propyl)phosphonic acid.
• Phosphonic Acids. III.¹ Hydroxyl Substituted Propylphosphonic Acids^2,3
  作者：Seymour Preis、Terrell C. Myers、Elwood V. Jensen

  DOI：10.1021/ja01628a050

  日期：1955.12
• HAMMERSCHMIDT, FRIEDRICH, MONATSH. CHEM., 122,(1991) N, C. 389-398
  作者：HAMMERSCHMIDT, FRIEDRICH

  DOI：——

  日期：——