(-)-(S)-1-phenyl-1-hydroxymethylphosphonic acid | 104944-23-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (-)-(S)-1-phenyl-1-hydroxymethylphosphonic acid
• 英文别名: (S)-(-)-(Phenylhydroxymethyl)phosphonic acid；(S)-1-phenyl-1-hydroxylmethylphosphonic acid；(S)-(hydroxy(phenyl)methyl)phosphonic acid；(S)-α-hydroxybenzylphosphonic acid；(S)-hydroxy(phenyl)methylphosphonic acid；hydroxy(phenyl)methylphosphonic acid；(1s)-a-Hydroxybenzylphosphonate；[(S)-hydroxy(phenyl)methyl]phosphonic acid
• CAS: 104944-23-2
• 化学式: C₇H₉O₄P
• 分子量: 188.12
• InChiKey: YLVXPXINUWURSG-ZETCQYMHSA-N

物化性质

• 熔点：
  226 °C
• 沸点：
  434.0±55.0 °C(Predicted)
• 密度：
  1.527±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 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：

  四甲基氢氧化铵 、 (-)-(S)-1-phenyl-1-hydroxymethylphosphonic acid 以 水 、 丙酮 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  Chiral, non-racemic α-hydroxyphosphonates and phosphonic acids via stereoselective hydroxylation of diallyl benzylphosphonates

  摘要：

  Chiral, non-racemic alpha-hydroxyphosphonates have been prepared in high enantiomeric excess (96-98% ee), via stereoselective oxaziridine-mediated hydroxylation of diallyl benzylphosphonates. The enantiomeric purity and absolute configuration of the alpha-hydroxyphosphonates was established from H-1 and P-31 NMR spectroscopy of the (S)-O-methylmandelate esters. Deprotection of the diallyl alpha-hydroxyphosphonates under neutral conditions furnished the corresponding free phosphonic acids, retaining a high degree of stereochemical purity (90 to >98% ee). (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(02)00786-3
• 作为产物：
  描述：

  benzylphosphonic dichloride 在 吡啶 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 sodium hexamethyldisilazane 、 5,5-二甲基-1,3-环己二酮 、 (+)-8,8-二氯樟脑磺哑嗪 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 (-)-(S)-1-phenyl-1-hydroxymethylphosphonic acid
  参考文献：
  名称：

  Chiral, non-racemic α-hydroxyphosphonates and phosphonic acids via stereoselective hydroxylation of diallyl benzylphosphonates

  摘要：

  Chiral, non-racemic alpha-hydroxyphosphonates have been prepared in high enantiomeric excess (96-98% ee), via stereoselective oxaziridine-mediated hydroxylation of diallyl benzylphosphonates. The enantiomeric purity and absolute configuration of the alpha-hydroxyphosphonates was established from H-1 and P-31 NMR spectroscopy of the (S)-O-methylmandelate esters. Deprotection of the diallyl alpha-hydroxyphosphonates under neutral conditions furnished the corresponding free phosphonic acids, retaining a high degree of stereochemical purity (90 to >98% ee). (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(02)00786-3

文献信息

• Substrate-Based Fragment Identification for the Development of Selective, Nonpeptidic Inhibitors of Striatal-Enriched Protein Tyrosine Phosphatase
  作者：Tyler D. Baguley、Hai-Chao Xu、Manavi Chatterjee、Angus C. Nairn、Paul J. Lombroso、Jonathan A. Ellman

  DOI：10.1021/jm401037h

  日期：2013.10.10

  Alzheimer’s disease. Herein, a substrate-based approach for the discovery and optimization of fragments called substrate activity screening (SAS) has been applied to the development of low molecular weight (<450 Da) and nonpeptidic, single-digit micromolar mechanism-based STEP inhibitors with greater than 20-fold selectivity across multiple tyrosine and dual specificity phosphatases. Significant levels of

  在许多神经精神疾病如阿尔茨海默病中观察到高水平的纹状体富集蛋白酪氨酸磷酸酶 (STEP) 活性。STEP 的过度表达导致许多关键神经元信号分子的去磷酸化和失活，包括离子型谷氨酸受体。此外，降低 AD 小鼠模型中 STEP 水平的基因显着逆转了认知缺陷并降低了谷氨酸受体内化。这些结果支持 STEP 作为治疗阿尔茨海默病药物发现的潜在靶点。在此，一种用于发现和优化称为底物活性筛选 (SAS) 的基于底物的方法已应用于低分子量 (<450 Da) 和非肽类的开发，基于单位数微摩尔机制的 STEP 抑制剂，对多种酪氨酸和双特异性磷酸酶的选择性超过 20 倍。还观察到大鼠皮层神经元中显着水平的 STEP 抑制。
• Enzymes in organic chemistry, part 1: Enantioselective hydrolysis of α-(acyloxy)phosphonates by esterolytic enzymes
  作者：Yong-Fu Li、Friedrich Hammerschmidt

  DOI：10.1016/s0957-4166(00)86021-8

  日期：1993.1

  exclusively hydrolyzed to give optically pure alcohols (S)-(−)-3a and (S)-(−)-3b. Lipases AP 6 and F-AP 15 were used to prepare phosphonates (S)-(−)-3b, (S)-(+)-3d and (S)-(−)-3e on a preparative scale with an enantiomeric excess of 81%, 87%, and 89%, respectively. The absolute configurations ofthe α-hydroxyphosphonates were assigned by Horeau's method and 1H-NMR spectroscopy of Mosher's derivatives

  制备α-羟基膦酸酯（±）-3并转化为酯（±）-5。测试了八种脂肪酶以及猪肝酯酶，作为双相系统中α-（酰氧基）膦酸酯的对映选择性水解的催化剂。他们中的两个被证明是有用的。以脂肪酶F-AP 15和α-（乙酰氧基）苯基甲基膦酸酯（±）-5a和（±）-5b为底物可获得最高的对映选择性。（S）-对映异构体专门水解，得到光学纯的醇（S）-（-）- 3a和（S）-（-）- 3b。脂肪酶AP 6和F-AP 15用于制备膦酸酯（S）-（-）- 3b，（S）-（+）- 3d和（S）-（-）- 3e在制备规模上，对映体过量分别为81％，87％和89％。α-羟基膦酸酯的绝对构型通过Horeau法和Mosher衍生物的1 H-NMR光谱确定。
• Synthesis of optically active hydroxyphosphonates
  作者：Irina Guliaiko、Vitaly Nesterov、Sergei Sheiko、Oleg I. Kolodiazhnyi、Matthias Freytag、Peter G. Jones、Reinhard Schmutzler

  DOI：10.1002/hc.20391

  日期：2008.3

  ketophosphonates was carried out by the chiral complex of NaBH4-L-proline, owing to the double asymmetric induction at the α-carbon atom. The hydroxyphosphonates obtained were isolated in a diastereomerically pure state and were transformed to the optically active, free hydroxyalkylphosphonic acids. The (R)-configuration of one of them was proved by X-ray crystal structure analysis. © 2008 Wiley Periodicals

  用硼氢化钠还原二薄荷基酮膦酸酯涉及在 α-碳原子上的不对称诱导，导致形成的 α-羟基膦酸酯的 (R)-对映体略过量。如果通过 NaBH4-L-脯氨酸的手性络合物进行手性二薄荷基酮膦酸酯的还原，由于在 α-碳原子上的双不对称诱导，可以获得更高的 ee 纯度。获得的羟基膦酸酯以非对映异构纯状态分离，并转化为旋光的游离羟基烷基膦酸。通过 X 射线晶体结构分析证明了其中之一的 (R)-构型。© 2008 Wiley Periodicals, Inc. 杂原子化学 19:133–139, 2008; 在线发表于 Wiley InterScience (www.interscience.wiley.com)。DOI 10.1002/hc.20391
• Enantioselective reduction of ketophosphonates using adducts of chiral natural acids with sodium borohydride
  作者：E.V. Gryshkun、V. Nesterov、O. I. Kolodyazhnyi

  DOI：10.3998/ark.5550190.0013.409

  日期：——

  asymmetric reduction of αand β ketophosphonates using chiral complexes prepared from sodium borohydride and natural aminoacids or tartaric acids was developed. Reduction of α or β ketophosphonates by these reagents led to formation of chiral (S)or (R)hydroxyphosphonates. Reduction of chiral di-(1R,2S,5R)-menthylketophosphonates by the chiral complexes NaBH4/(R,R)-proline or NaBH4/(R,R)-tartaric acid due to

  开发了一种使用由硼氢化钠和天然氨基酸或酒石酸制备的手性配合物不对称还原 α 和 β 酮膦酸酯的方法。这些试剂还原 α 或 β 酮膦酸酯导致手性 (S) 或 (R) 羟基膦酸酯的形成。由于双匹配不对称诱导，手性复合物 NaBH4/(R,R)-脯氨酸或 NaBH4/(R,R)-酒石酸还原手性二-(1R,2S,5R)-薄荷基酮膦酸酯导致立体选择性增加反应并导致羟基膦酸酯的形成高达 90% ee 或更高。使用 2-羟基-3 氯丙基膦酸二甲酯作为制备多克数量的多种生物活性化合物的 chiron。
• Efficient method for the asymmetric reduction of α- and β-ketophosphonates
  作者：V.V. Nesterov、O.I. Kolodiazhnyi

  DOI：10.1016/j.tet.2007.04.101

  日期：2007.7

  versatile method for the asymmetric reduction of α- and β-ketophosphonates using chiral reactant derived from sodium borohydride and l-(+)- or d-(−)-tartaric acid is developed. The methodology was used for the preparation of a number of biologically interesting enantiomerically pure products: including 2,3-epoxypropylphosphonate 11, 2-hydroxy-3-aminopropylphosphonic acid 14 (phospho-GABOB), phospho-carnitine

  开发了一种高效且通用的方法，该方法使用衍生自硼氢化钠和1-（+）-或d-（-）-酒石酸的手性反应物不对称还原α-和β-酮膦酸酯。该方法被用于许多生物有趣对映体纯产品的制备：含2,3- epoxypropylphosphonate 11，2-羟基-3-氨基丙基膦酸14（磷酸- GABOB），磷酸-肉碱19，和其他在多克规模。