N-benzyloxycarbonyl-D-phosphoalanine dimethyl ester | 241496-50-4

• 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: N-benzyloxycarbonyl-D-phosphoalanine dimethyl ester
• 英文别名: (S)-(+)-1-(benzyloxycarbonylamino)-1-dimethylphosphonylethane；(S)-1-(N-benzyloxycarbonylamino)ethylphosphonic acid dimethyl ester；benzyl N-[1-(dimethoxyphosphoryl)ethyl]carbamate；(S)-benzyl (1-(dimethoxyphosphoryl)ethyl)carbamate；benzyl N-[(1S)-1-dimethoxyphosphorylethyl]carbamate
• CAS: 241496-50-4
• 化学式: C₁₂H₁₈NO₅P
• 分子量: 287.252
• InChiKey: ZSMIGAVXKKRMRJ-JTQLQIEISA-N

物化性质

• 沸点：
  422.5±38.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-benzyloxycarbonyl-D-phosphoalanine dimethyl ester 、 7-bromo-5-bromomethyl-2,3-dimethoxy-quinoxaline 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以50%的产率得到benzyl N-[(7-bromo-2,3-dimethoxyquinoxalin-5-yl)methyl]-N-[(1S)-1-[dimethoxy(oxido)phosphaniumyl]ethyl]carbamate
  参考文献：
  名称：

  Synthesis, radiolabelling and biological characterization of ( d )-7-iodo- N -(1-phosphonoethyl)-5-aminomethylquinoxaline-2,3-dione, a glycine-binding site antagonist of NMDA receptors

  摘要：

  (D)-7-碘-N-(1-膦乙基)-5-氨基甲基喹喔啉-2,3-二酮（I-PAMQX）是一种具有强效活性和体内活性的拮抗剂，作用于NMDA受体复合体的甘氨酸结合位点。通过从其7-溴类似物出发，以良好的收率和高比活度制备了放射性碘标记的[ I-131]I-PAMQX。在小鼠中进行的[ I-131]I-PAMQX生物分布研究显示，该化合物在血液中的清除相对缓慢。肾脏的放射性摄取量最高，而心脏、肺、肝脏和骨骼的摄取量中等，脑中的摄取量较低。版权归属1999 Elsevier Science Ltd. 保留所有权利。

  DOI：

  10.1016/s0960-894x(99)00576-4
• 作为产物：
  描述：

  dimethyl [1-(benzyloxycarbonylamino)ethen-1-yl]phosphonate 在 bis(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate 、 C₃₆H₃₂N₃O₃P 、 氢气 作用下， 以 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 1.0h， 生成 N-benzyloxycarbonyl-D-phosphoalanine dimethyl ester
  参考文献：
  名称：

  α-和β-氨基膦酸酯的不对称氢化：铑（I）/单齿亚磷酰胺催化剂

  摘要：

  使用单亚磷酰胺作为手性配体，在Rh I催化的α-和β-氨基膦酸酯的不对称氢化中实现了高效率和对映选择性（参见方案； cod = 1,5-环辛二烯），从而提供了光学活性的氨基膦酸酯具有高达1800 h -1的周转频率和高ee 值。

  DOI：

  10.1002/anie.201104912

文献信息

• Asymmetric Hydrogenation with Highly Active IndolPhos-Rh Catalysts: Kinetics and Reaction Mechanism
  作者：Jeroen Wassenaar、Mark Kuil、Martin Lutz、Anthony L. Spek、Joost N. H. Reek

  DOI：10.1002/chem.200903476

  日期：2010.6.11

  The mechanism of the IndolPhos–Rh‐catalyzed asymmetric hydrogenation of prochiral olefins has been investigated by means of X‐ray crystal structure determination, kinetic measurements, high‐pressure NMR spectroscopy, and DFT calculations. The mechanistic study indicates that the reaction follows an unsaturate/dihydride mechanism according to Michaelis–Menten kinetics. A large value of KM (KM=5.01±0

  通过X射线晶体结构测定，动力学测量，高压NMR光谱和DFT计算，研究了IndolPhos–Rh催化的前手性烯烃不对称氢化的机理。机理研究表明，根据米利斯（Michaelis-Menten）动力学，该反应遵循不饱和/二氢键机理。K M的较大值（K M = 5.01±0.16  M），表明Rh-溶剂合物是催化剂的静止状态，已通过高压NMR光谱观察到。通过实验手段无法检测到的底物-催化剂复合物的DFT计算表明，主要的底物-催化剂复合物导致了产物。这种机理与先前关于与C 1对称的异位和单齿配体的不对称氢化反应机理的研究一致。
• An easy entry to optically active α-amino phosphonic acid derivatives using phase-transfer catalysis (PTC)
  作者：Francesco Fini、Gabriele Micheletti、Luca Bernardi、Daniel Pettersen、Mariafrancesca Fochi、Alfredo Ricci

  DOI：10.1039/b807027j

  日期：——

  The unprecedented use of phase-transfer catalysis (PTC) in an asymmetric hydrophosphonylation reaction allows the obtainment of a range of optically active α-amino phosphonic acid derivatives directly from α-amido sulfones.

  在不对称亲水磷腈反应中空前绝后地使用相转移催化（PTC），使得直接从α-酰胺砜获得一系列光学活性的α-氨基膦酸衍生物成为可能。
• Chiral 1,2,3,4-Tetrahydro-1-naphthylamine-Derived Phosphine-Phosphoramidite Ligand (THNAPhos): Application in Highly Enantioselective Hydrogenations of Functionalized CC Bonds
  作者：Min Qiu、Xiang-Ping Hu、Dao-Yong Wang、Jun Deng、Jia-Di Huang、Sai-Bo Yu、Zheng-Chao Duan、Zhuo Zheng

  DOI：10.1002/adsc.200800152

  日期：2008.6.9

  reported a new chiral 1,2,3,4-tetrahydro-1-naphthylamine-derived phosphine-phosphoramidite ligand, (Rc,Ra)-THNAPhos, that is highly efficient in the rhodium-catalyzed asymmetric hydrogenation of a broad range of α-enol ester phosphonates. To further demonstrate the utility of THNAPhos in asymmetric hydrogenation, in this paper, we describe its new application in the asymmetric hydrogenation of α-dehydroamino

  我们最近报道了一种新的手性1,2,3,4-四氢-1-萘胺衍生的膦-亚磷酰胺配体（R c，R a）-THNAPhos，在铑催化的aa的不对称加氢中非常有效范围广泛的α-烯醇酯膦酸酯。为了进一步证明THNAPhos在不对称氢化中的效用，在本文中，我们描述了其在α-脱氢氨基酸酯，酰胺，衣康酸二甲酯和α-烯酰胺膦酸酯的不对称氢化中的新应用。结果表明，Rh /（R c，R a）-THNAPhos络合物对于这些类型的功能化CC烯烃的对映选择性氢化非常有效，从而以优异的对映选择性（通常超过99％ee）提供相应的氢化产物。
• The Synthesis of α-Aminophosphonates via Enantioselective Organocatalytic Reaction of 1-(N-Acylamino)alkylphosphonium Salts with Dimethyl Phosphite
  作者：Alicja Walęcka-Kurczyk、Krzysztof Walczak、Anna Kuźnik、Sebastian Stecko、Agnieszka Październiok-Holewa

  DOI：10.3390/molecules25020405

  日期：——

  an effective method for this type of transformation using a racemic mixture of starting N-protected α-amino acids and a chiral catalyst. Herein, a simple and efficient stereoselective organocatalytic α-amidoalkylation of dimethyl phosphite by 1-(N-acylamino)alkyltriphenylphosphonium salts to enantiomerically enriched α-aminophosphonates is reported. Using 5 mol% of chiral quinine- or hydroquinine-derived

  α-氨基膦酸是α-氨基酸的磷类似物。由于其独特的生物活性，这种类型的化合物在医学和作物保护中有着广泛的应用。这些活动中的一个关键因素是立体异构体的构型。迄今为止，只有少数将 α-氨基酸立体选择性地转化为磷类似物的方法是已知的，而且所有方法都基于不对称诱导，因此涉及手性底物的使用。相比之下，我们专注于开发一种使用起始 N-保护的 α-氨基酸和手性催化剂的外消旋混合物进行此类转化的有效方法。在此处，报道了通过 1-（N-酰基氨基）烷基三苯基鏻盐对亚磷酸二甲酯进行简单有效的立体选择性有机催化 α-酰胺烷基化反应生成对映体富集的 α-氨基膦酸酯。使用 5 mol% 的手性奎宁或氢奎宁衍生的季铵盐，最终产品的产率高达 98%，ee 高达 92%。起始鏻盐很容易从α-氨基酸衍生物通过脱羧甲氧基化和随后用三苯基鏻四氟硼酸盐取代获得。通过非手性快速色谱对选定的 α-氨基膦酸酯衍生物进行适当的对映体自歧化 (SDE)
• Penicillin G acylase-mediated kinetic resolution of racemic 1-( N -acylamino)alkylphosphonic and 1-( N -acylamino)alkylphosphinic acids and their esters
  作者：Katarzyna Zielińska、Roman Mazurkiewicz、Katarzyna Szymańska、Andrzej Jarzębski、Sylwia Magiera、Karol Erfurt

  DOI：10.1016/j.molcatb.2016.05.011

  日期：2016.10

  Extensive studies on the penicillin G acylase-mediated kinetic resolution of N-acylated 1-aminoalkylphosphonic and 1-aminoalkylphosphinic acids as well as their esters were carried out to recognise the relationships between the substrate structure, reaction conditions, and the enzymatic hydrolytic deacylation efficiency and stereoselectivity. Reactivity of 1-(N-acylamino)alkylphosphonic and 1-(N-acylamino)allcylphosphinic acids and their esters in the penicillin G acylase-mediated hydrolytic deacylation reaction depends strongly on the kind of their N-acyl group, with high preference to the hydrolytic splitting of the N-phenylacetyl moiety. The initial hydrolysis rates of 1-(N-phenylacetylamino)alkylphosphonic acid dimethyl esters 2 are mostly distinctly lower in comparison with the corresponding free acids 3 and rapidly decrease with the increasing steric effect of the substituent at the alpha-position. In contrary to the substituents at the alpha-carbon, bulky substituents at the phosphorus hinder the enzymatic hydrolysis to a much lesser degree. The penicillin G acylase-mediated stereospecific hydrolysis of N-acyl group of both racemic 1-(N-acylamino)alkylphosphonic acids 3 and their dimethyl esters 2 proved to be, in most cases, a highly effective method for the kinetic resolution of these compounds: High enzyme enantioselectivity E-values exceeding 100, or synthetically useful E-values exceeding 20 (in two cases) were obtained for the N-acylated phosphonic acid analogues of alanine, phenylalanine, valine, leucine, and asparagine, as well as for their dimethyl esters, with the exception of the dimethyl ester of phosphonic analogue of valine 2e, that E-value was low (E=1.2). Also for the N-acylated H-phosphinic acid analogues of alanine, as well as phenylphosphinic acid analogue of alanine, high enzyme enantioselectivity values exceeding 100 were obtained. In contrary, E-values for both diastereomers of ethyl ester of phenylphosphinic analogue of alanine 2k were low (E=7 and 13). For the all accomplished assignments penicillin G acylase exhibited stereochemical preference for the (R)-substrate. (C) 2016 Elsevier B.V. All rights reserved.