diisopropyl (S)-α-hydroxypropylphosphonate | 173035-34-2

• 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: diisopropyl (S)-α-hydroxypropylphosphonate
• 英文别名: (S)-diisopropyl-1-hydroxypropanephosphonate；Phosphonic acid, [(1S)-1-hydroxypropyl]-, bis(1-methylethyl) ester；(1S)-1-di(propan-2-yloxy)phosphorylpropan-1-ol
• CAS: 173035-34-2
• 化学式: C₉H₂₁O₄P
• 分子量: 224.237
• InChiKey: OCIVRRRKMDNEOG-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  diisopropyl (S)-α-hydroxypropylphosphonate 在 4-二甲氨基吡啶 、 18-冠醚-6 、 potassium thioacyanate 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 58.08h， 生成 (R)-diisopropyl 1-(methylsulfanyl)propylphosphonate
  参考文献：
  名称：

  Synthesis of chiral, nonracemic α-sulfanylphosphonates and derivatives

  摘要：

  Optically active alpha-sulfanylphosphonates and the corresponding methyl sulfides were prepared in three steps starting from chiral, nonracemic (ee 93-97%) alpha-hydroxyphosphonates obtained by enzymatic resolution. Reaction conditions for the reduction of racemisation-prone substrates were found to preserve the enantiomeric excesses. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(03)00316-1
• 作为产物：
  描述：

  Acetic acid (S)-1-(diisopropoxy-phosphoryl)-propyl ester 在 三乙胺 作用下， 以 甲醇 、 水 为溶剂， 生成 diisopropyl (S)-α-hydroxypropylphosphonate
  参考文献：
  名称：

  有机化学中的酶，第11期：[1]水解酶催化的α-和β-羟基膦酸酯的拆分以及手性，非自由基的β-氨基膦酸的合成

  摘要：

  外消旋二异丙基α-和β-羟基膦酸酯在叔丁基甲基醚中通过水解酶与乙酸异丙烯酯作为酰基供体的对映选择性酰化受到酶狭窄的底物特异性的限制。对于（S）-二异丙基1-羟基-（2-噻吩基）甲基-，1-羟乙基-和1-羟己基膦酸酯和（R）-二异丙基2-羟丙基膦酸酯的乙酸酯，获得高对映体过量（至多99％）。双相系统中念珠菌和蛋白酶枯草杆菌蛋白酶对脂肪酶水解多种β-氯乙酰氧基膦酸酯的作用是对映体选择性的（S）-β-羟基膦酸酯（ee 51–92％）。（S）-2-苯基-2-羟乙基-和（S）-3-甲基-2-羟基丁基膦酸酯（ee分别为96％和99％）被转化为相同ee的（R）-2-氨基膦酸。

  DOI：

  10.1002/adsc.200303135

文献信息

• Enzymes in Organic Chemistry; Part 3: Enantioselective Hydrolysis of 1-Acyloxyalkylphosphonates by Lipase from Aspergillus niger (Lipase AP 6)
  作者：Martina Drescher、F. Hammerschmidt、Hanspeter Kählig

  DOI：10.1055/s-1995-4083

  日期：1995.10

  Racemic α-acyloxyalkylphosphonates (±)-4 are prepared and tested for kinetic resolution by lipases AP 6 and to a minor extent by F-AP 15. The former proves to be a useful enzyme in terms of broadness of application, reaction rate and enantiomeric excess. Lipase F-AP 15 transformed neither of the two substrates checked for hydrolysis. Enzymatic hydrolysis of α-acyloxyphosphonates containing straight chain alkyl groups with lipase AP 6 yields (S)-α-hydroxyalkylphosphonates 3 preferentially. Substrates with branched chain alkyl groups are hydrolysed with lower enantioselectivity, the (R)-ester being saponified more easily than the (S)-ester.

  制备了外消旋δ-±-乙酰氧基烷基膦酸盐 (±)-4，并通过脂肪酶 AP 6 和少量 F-AP 15 进行了动力学解析测试。前者在应用广泛性、反应速度和对映体过量方面被证明是一种有用的酶。脂肪酶 F-AP 15 对两种底物都没有进行水解转化。用脂肪酶 AP 6 对含有直链烷基的 δ-acyloxyphosphonates 进行酶水解，可优先生成 (S)-δ-hydroxyalkylphosphonates 3。含有支链烷基的底物水解的对映选择性较低，(R)-酯比(S)-酯更容易被皂化。
• Enzymatic synthesis of phosphocarnitine, phosphogabob and fosfomycinStudies on organophosphorus compounds. Part 128. For Part 127, see C. Yuan, C. Xu and Y. Zhang, Tetrahedron, 2003, 59, 6095.
  作者：Ke Wang、Yonghui Zhang、Chengye Yuan

  DOI：10.1039/b307638p

  日期：——

  Phosphocarnitine was conveniently obtained from easily available diethyl 3-chloro-2-oxopropanephosphonates, followed by subsequent reduction, Mucor miehei lipase (IM) mediated resolution, amination and dealkylation. Candida antarctica lipase B (CALB) served as an effective biocatalyst in the resolution of several 1- or 2- hydroxyalkanephosphonates. The chlorine atom in different positions on the molecules greatly affected their enantioselectivity. CALB also showed satisfactory enantioselectivity toward those molecules bearing an azido moiety. Both enantiomers of phosphogabob and fosfomycin were also prepared via CALB-mediated resolution as the key step.

  从易于获得的 3-氯-2-氧代丙烷膦酸二乙酯中方便地获得了磷卡尼汀，随后进行了还原、Mucor miehei 脂肪酶（IM）介导的解析、胺化和脱烷基化。白色念珠菌脂肪酶 B（CALB）是一种有效的生物催化剂，可用于多种 1-或 2-羟基烷基膦酸盐的分解。分子上不同位置的氯原子极大地影响了它们的对映选择性。CALB 对含有叠氮基的分子也表现出令人满意的对映选择性。磷霉素和磷霉素的两种对映体也都是通过 CALB 介导的解析作为关键步骤制备的。
• Enzymes in organic chemistry. Part 9: Chemo-enzymatic synthesis of phosphonic acid analogues of l-valine, l-leucine, l-isoleucine, l-methionine and l-α-aminobutyric acid of high enantiomeric excess
  作者：Friedrich Hammerschmidt、Frank Wuggenig

  DOI：10.1016/s0957-4166(99)00152-4

  日期：1999.5

  2-dimethylpropane-1,3-diyl group increased the reaction rate. (S)-α-Hydroxyphosphonates (ee 92–99%), obtained with the protease except one, were transformed into phosphonic acid analogues of l-valine, l-leucine, l-isoleucine, l-methionine and l-α-aminobutyric acid. Their enantiomeric purity was determined by HPLC on a chiral stationary phase after derivatisation at nitrogen.

  通过酶催化水解拆分衍生自丙醛，异丁醛，3-甲基巯基丙醛，3-甲基丁醛和（S）-2-甲基丁醛的二异丙基α-氯乙酰氧基膦酸酯。脂肪酶优选水解的（小号） -酯和蛋白酶固定化脂肪酶® P-2的（- [R ）-酯。用叔丁基取代异丙基降低了反应速率；用2，2-二甲基丙烷-1，3-二基取代它们可以提高反应速率。（S用一种蛋白酶获得的）-α-羟基膦酸酯（ee 92–99％）被转化为l-缬氨酸，l-亮氨酸，l-异亮氨酸，l-蛋氨酸和l-α-氨基丁酸的膦酸类似物。它们的对映体纯度是在氮气下衍生化后，在手性固定相上通过HPLC测定的。
• Enzymes in Organic Chemistry, 11:[1] Hydrolase-Catalyzed Resolution ofα- andβ-Hydroxyphosphonates and Synthesis of Chiral, Non-Racemicβ-Aminophosphonic Acids
  作者：A. Woschek、Wolfgang Lindner、F. Hammerschmidt

  DOI：10.1002/adsc.200303135

  日期：2003.12

  enantioselective acylation of racemic diisopropyl α- and β-hydroxyphosphonates by hydrolases in t-butyl methyl ether with isopropenyl acetate as acyl donor is limited by the narrow substrate specificity of the enzymes. High enantiomeric excesses (up to 99%) were obtained for the acetates of (S)-diisopropyl 1-hydroxy-(2-thienyl)methyl-, 1-hydroxyethyl- and 1-hydroxyhexylphosphonate and (R)-diisopropyl 2-hydroxypropylphosphonate

  外消旋二异丙基α-和β-羟基膦酸酯在叔丁基甲基醚中通过水解酶与乙酸异丙烯酯作为酰基供体的对映选择性酰化受到酶狭窄的底物特异性的限制。对于（S）-二异丙基1-羟基-（2-噻吩基）甲基-，1-羟乙基-和1-羟己基膦酸酯和（R）-二异丙基2-羟丙基膦酸酯的乙酸酯，获得高对映体过量（至多99％）。双相系统中念珠菌和蛋白酶枯草杆菌蛋白酶对脂肪酶水解多种β-氯乙酰氧基膦酸酯的作用是对映体选择性的（S）-β-羟基膦酸酯（ee 51–92％）。（S）-2-苯基-2-羟乙基-和（S）-3-甲基-2-羟基丁基膦酸酯（ee分别为96％和99％）被转化为相同ee的（R）-2-氨基膦酸。
• Synthesis of chiral, nonracemic α-sulfanylphosphonates and derivatives
  作者：Mihaela Gulea、Friedrich Hammerschmidt、Patrice Marchand、Serge Masson、Violeta Pisljagic、Frank Wuggenig

  DOI：10.1016/s0957-4166(03)00316-1

  日期：2003.7

  Optically active alpha-sulfanylphosphonates and the corresponding methyl sulfides were prepared in three steps starting from chiral, nonracemic (ee 93-97%) alpha-hydroxyphosphonates obtained by enzymatic resolution. Reaction conditions for the reduction of racemisation-prone substrates were found to preserve the enantiomeric excesses. (C) 2003 Elsevier Science Ltd. All rights reserved.