N-benzyloxycarbonyl-1-aminoethanephosphonic acid methyl monoester | 61989-17-1

• 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-1-aminoethanephosphonic acid methyl monoester
• 英文别名: methyl hydrogen 1-{[(benzyloxy)carbonyl]amino}ethylphosphonate；methyl (1R,S)-1-[(N-benzyloxycarbonyl)amino]ethyl phosphonate；methyl hydrogen 1-(benzyloxycarbonylamino)ethylphosphonate；methyl 1-(N-benzyloxycarbonylaminoethyl)phosphonate；methyl 1-(benzyloxycarbonylamino)ethyl phosphonate；[1-(hydroxy-methoxy-phosphoryl)-ethyl]-carbamic acid benzyl ester；Methoxy-[1-(phenylmethoxycarbonylamino)ethyl]phosphinic acid
• CAS: 61989-17-1
• 化学式: C₁₁H₁₆NO₅P
• 分子量: 273.226
• InChiKey: LKFYLGJTOQMUQN-UHFFFAOYSA-N

物化性质

• 熔点：
  120-123 °C
• 密度：
  1.285±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-benzyloxycarbonyl-1-aminoethanephosphonic acid methyl monoester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 (1-amino-ethyl)-phosphonic acid monomethyl ester
  参考文献：
  名称：

  Synthesis of New Lipophilic Phosphonate and Phosphonamidate Analogues of N-Acetylmuramyl-L-alanyl-D-isoglutamine Related to LK 423

  摘要：

  本文介绍了三种与LK 423相关的新型肽聚糖二肽（MDP）类似物，作为潜在的免疫调节剂。通过用磷酰胺异构体替代L-丙氨酸和D-谷氨酸（或D-异谷氨酸）之间的酰胺键，修改了主要化合物的二肽部分，得到新的MDP类似物5和9。此外，L-丙氨酸和D-谷氨酸之间的酰胺键被磷酸酯异构体替代，生成了肽磷酸酯14。讨论了所采用合成策略的范围和局限性。

  DOI：

  10.3390/70400394
• 作为产物：
  描述：

  氨基甲酸苄酯 在 甲醇 、 水 、 溶剂黄146 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 20.0h， 生成 N-benzyloxycarbonyl-1-aminoethanephosphonic acid methyl monoester
  参考文献：
  名称：

  Synthesis, characterization and activity of new phosphonate dipeptides as potential inhibitors of VanX

  摘要：

  VanX, a Zn(II)-dependent D-ala-D-ala dipeptidase, is essential for vancomycin resistance in Enterococcus faecium. The enzymatic activity of VanX was previously found to be inhibited competitively by 2-{[(1-aminoethyl) (hydroxy) phosphoryl]oxy} propanoic acid (1B). Here we report the synthesis and characterization of seven phosphonate dipeptide analogs of D-ala-D-ala with various substituent, the activity evaluation indicated that six of these phosphonate analogs inhibit VanX with IC50 of 0.48-8.21 mM. These data revealed a structure-activity relationship which is that the large substituent group on beta-carbon resulted in low binding affinity of the phonphonate analog to VanX. This information will be helpful to guide the design and synthesis of the tightly-binding inhibitors for VanX. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.10.094

文献信息

• Studies on Organophosphorus Compounds XLVII: Acetyl Chloride - A Versatile Reagent for the Synthesis of 1-Aminoalkyl- and Amino(aryl)methylphosphonic Acid Derivatives
  作者：Chengye Yuan、Shoujun Chen、Guohong Wang

  DOI：10.1055/s-1991-26503

  日期：——

  Acetyl chloride is used successfully in the synthesis of 1-aminoalkyl- and amino(aryl)methylphosphonic acid derivatives by a three-component condensation reaction involving diethyl phosphoramidate, aldehydes and diphenyl phosphite. Furthermore, in the reaction of benzyl carbamate, aldehydes and phosphorus(III) chloride, acetyl chloride facilates the formation of alkyl hydrogen 1-(benzyloxycarbonylamino)alkylphosphonates or aryl(benzyloxycarbonylamino) methylphosphonates, key intermediates in the synthesis of phosphonopeptide with a P-N bond. In comparison with other methods, the present variation affords wider scope of application including the use of some aliphatic aldehydes, fair yields and mild reaction conditions.

  乙酰氯被成功用于通过涉及磷酰胺酸二乙酯、醛和亚磷酸二苯酯的三组分缩合反应合成 1-氨基烷基和氨基（芳基）甲基膦酸衍生物。 此外，在氨基甲酸苄酯、醛类和氯化磷（III）的反应中，乙酰氯有助于形成烷基氢 1-（苄氧羰基氨基）烷基膦酸盐或芳基（苄氧羰基氨基）甲基膦酸盐，它们是合成具有 P-N 键的膦肽的关键中间体。与其他方法相比，本变体具有更广泛的应用范围，包括使用一些脂肪族醛、较高的产率和温和的反应条件。
• A One-Pot Conversion of α-Aminoalkylphosphonous Acids into Monomethyl α-Aminoalkylphosphonates
  作者：Stanislav Gobec、Katja Štrancar

  DOI：10.1055/s-2004-815922

  日期：——

  An excellent method for a one-pot conversion of N-protected α-aminoalkylphosphonous acids into the corresponding monomethyl phosphonates, using thionyl chloride in methanol, has been devised. N-Protected monomethyl α-aminoalkylphosphonates are valuable intermediates in the preparation of phosphapeptides.

  设计了一种使用甲醇中的亚硫酰氯将 N-保护的 α-氨基烷基膦酸一锅转化为相应的膦酸单甲酯的极好方法。 N-保护的单甲基α-氨基烷基膦酸酯是制备磷酸肽的有价值的中间体。
• Phosphonamidate and phosphothioate dipeptides as potential inhibitors of VanX
  作者：Ke-Wu Yang、Jeffrey J. Brandt、Lisa L. Chatwood、Michael W. Crowder

  DOI：10.1016/s0960-894x(00)00186-4

  日期：2000.5

  In an effort to prepare novel inhibitors of VanX, N-[(1-aminoethyl)hydroxyphosphinyl]-D-alanine 1 and S-[(aminoethyl)hydroxyphosphinyl]-thiolacetic acid 2 were synthesized and evaluated as inhibitors of VanX. Phosphonamidate 1 was shown to be a partial competitive inhibitor of VanX with a Ki of 36+/-3 microM, and phosphothioate 2 was shown not to inhibit VanX.

  为了制备新的VanX抑制剂，合成了N-[（（1-氨基乙基）羟基次膦基] -D-丙氨酸1和S-[（（氨基乙基）羟基次膦基]硫代乙酸2]并评价为VanX的抑制剂。磷酰胺酯1被证明是VanX的部分竞争性抑制剂，Ki为36 +/- 3 microM，硫代磷酸酯2被证明不抑制VanX。
• Towards new inhibitors of D-alanine:D-alanine ligase: The synthesis of 3-amino butenylphosphonic and aminophosphonamidic acids.
  作者：Y. Vo-Quang、A.M. Gravey、R. Simonneau、L. Vo-Quang、A.M. Lacoste、F. Le Goffic

  DOI：10.1016/s0040-4039(00)61837-3

  日期：1987.1

  The condensation of sodium salt of tetraethyl methylenediphosphonate with N-Cbz alaninal followed by the standard acidolytic removal of protecting groups provides an efficient method for the synthesis of 3-aminobutenylphosphonic acid E ; N-Cbz-aminophosphonamidic acid was prepared from diphenyl 1-amino ethylphosphonic acid through methyl phosphochloridate alanine methyl ester condensation in the presence

  亚甲基二膦酸四乙酯钠盐与N-Cbz丙氨酸缩合，然后标准酸解除去保护基团，为合成3-氨基丁烯基膦酸E提供了一种有效的方法。在三乙胺和碱性部分脱保护的条件下，由二苯基1-氨基乙基膦酸通过氯膦酸甲酯丙氨酸甲酯缩合制得N-Cbz-氨基膦酰胺酸。
• Phosphonic acid derivative having inhibitory activity against carboxypeptidase B
  申请人：Meiji Seika Kaisha Ltd.

  公开号：US20030119787A1

  公开（公告）日：2003-06-26

  A compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof: 1 wherein R 1 represents hydrogen atom, an alkyl group, a substituted alkyl group and the like; R 2 and R 3 represent hydrogen atom, an alkyl group, a substituted alkyl group, an alkoxyl group and the like; X represents —CH 2 —, —O—, or —NH—; A represents the following group (II): 2 [in which R 7 and R 8 represent hydrogen atom, an alkyl group, an acyl group, an alkoxycarbonyl group and the like; R 9 and R 10 represents hydrogen atom, a halogen atom, hydroxyl group, phenyl group, an alkyl group and the like] and the like; and E represents hydrogen atom and the like, which has inhibitory activity against carboxypeptidase B and is useful for therapeutic and/or preventive treatment of a thrombotic disease.

  以下是通用式（I）及其药学上可接受的盐所代表的化合物：其中R1代表氢原子、烷基、取代烷基等；R2和R3代表氢原子、烷基、取代烷基、烷氧基等；X代表—CH2—、—O—或—NH—；A代表以下基团（II）：其中R7和R8代表氢原子、烷基、酰基、烷氧羰基等；R9和R10代表氢原子、卤素原子、羟基、苯基、烷基等；E代表氢原子等，具有对羧肽酶B的抑制活性，可用于治疗和/或预防血栓性疾病。