benzyl N-[1-[chloro(methoxy)phosphoryl]ethyl]carbamate | 107072-65-1

• 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: benzyl N-[1-[chloro(methoxy)phosphoryl]ethyl]carbamate
• CAS: 107072-65-1
• 化学式: C₁₁H₁₅ClNO₄P
• 分子量: 291.671
• InChiKey: GDEOLCLMRPQWAY-UHFFFAOYSA-N

物化性质

• 密度：
  1.288±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 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：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl N-[1-[chloro(methoxy)phosphoryl]ethyl]carbamate 在 六甲基磷酰三胺 、 三乙基碳酸氢铵缓冲液 、 lithium thiopropiolate 、 三乙胺 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 242.0h， 生成 2-[Hydroxy-[1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]sulfanylacetic acid
  参考文献：
  名称：

  磷酰胺盐和硫代磷酸酯二肽是VanX的潜在抑制剂。

  摘要：

  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。

  DOI：

  10.1016/s0960-894x(00)00186-4
• 作为产物：
  描述：

  diphenyl 1-(phenylmethoxycarbonylamino)ethyl phosphonate 在 氯化亚砜 、 sodium iodide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 4.08h， 生成 benzyl N-[1-[chloro(methoxy)phosphoryl]ethyl]carbamate
  参考文献：
  名称：

  潜在的VanX抑制剂膦酰胺二肽的合成及活性研究

  摘要：

  为了开发VanX抑制剂，d -Ala- d -Ala二肽，N -[（（1-氨基乙基）羟基膦基]]-甘氨酸（1a），-丙氨酸（1b），-缬氨酸（1c）的膦酰胺类似物，使用重组VanX合成，表征和评估了-亮氨酸（1d）和-苯丙氨酸（1e）。获得了中间体6d的晶体结构（沉积编号：CCDC 839134），结构分析表明，该晶体为正交晶，空间群为P2（1）2（1）2（1），PN的键长为1.62Å，C–N–P角为123.6°。磷酰胺酯1（a–e）证明是VanX的抑制剂，IC 50值分别为0.39、0.70、1.12、2.82和4.13 mM，这表明磷酸氨基酰胺的抑制活性取决于它们的R取代基的大小，其中最好的抑制剂具有最小取代基的1a。此外，1a对金黄色葡萄球菌（ATCC 25923）表现出抗菌活性，MIC值为0.25μg/ ml。

  DOI：

  10.1016/j.bmcl.2011.09.020

文献信息

• 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。
• Inhibition of tRNA-dependent ligase MurM from Streptococcus pneumoniae by phosphonate and sulfonamide inhibitors
  作者：Elena Cressina、Adrian J. Lloyd、Gianfranco De Pascale、B. James Mok、Stephen Caddick、David I. Roper、Christopher G. Dowson、Timothy D.H. Bugg

  DOI：10.1016/j.bmc.2009.03.028

  日期：2009.5

  Ligase MurM catalyses the addition of Ala from alanyl-tRNA(Ala), or Ser from seryl-tRNA(Ser), to lipid intermediate II in peptidoglycan biosynthesis in Streptococcus pneumoniae, and is a determinant of high-level penicillin resistance. Phosphorus-based transition state analogues were designed as inhibitors of the MurM-catalysed reaction. Phosphonamide analogues mimicking the attack of a lysine nucleophile upon Ala-tRNA(Ala) showed no inhibition of MurM, but adenosine 3'-phosphonate analogues showed inhibition of MurM, the most active being a 2'-deoxyadenosine analogue (IC50 100 mu M). Structure/function studies upon this analogue established that modi. cation of the amino group of the aminoalkylphosphonate resulted in loss of potency, and modi. cation of the adenosine 5'-hydroxyl group with either a t-butyl dimethyl silyl or a carbamate functional group resulted in loss of activity. A library of 48 aryl sulfonamides was also screened against MurM using a radiochemical assay, and two compounds showed sub-millimolar inhibition. These compounds are the first small molecule inhibitors of the Fem ligase family of peptidyltransferases found in Gram-positive bacteria. (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis, characterization and activity of new phosphonate dipeptides as potential inhibitors of VanX
  作者：Chao Jia、Ke-Wu Yang、Cheng-Cheng Liu、Lei Feng、Jian-Min Xiao、Li-Sheng Zhou、Yi-Lin Zhang

  DOI：10.1016/j.bmcl.2011.10.094

  日期：2012.1

  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.
• Bartlett, Paul A.; Marlowe, Charles K., Phosphorus and Sulfur and the Related Elements, 1987, vol. 30, p. 537 - 544
  作者：Bartlett, Paul A.、Marlowe, Charles K.

  DOI：——

  日期：——
• Time-dependent inhibition of Streptococcus faecalisd-alanine: d-alanine ligase by α-aminophosphonamidic acids
  作者：AM Lacoste、AM Chollet-Gravey、L Vo Quang、Y Vo Quang、F Le Goffic

  DOI：10.1016/0223-5234(91)90057-t

  日期：1991.4

  Some alpha-aminophosphonamidates which may mimic the transition state of D-alanine: D-alanine ligase catalytic reaction have been synthesized. The inhibition of the ligase by these compounds was investigated with Streptococcus faecalis enzyme using [C-14]-D-Ala assay. Apparent K(i) values analyzed by Dixon plots are in the same range as the apparent K(m). These compounds exhibit a time-dependent inhibition in the presence of ATP, suggesting that they undergo phosphorylation prior to inactivating the enzyme. The (enzyme-inhibitor-ATP) complex apparently dissociates very slowly, showing a process of slow binding inhibition. These results are consistent with the mechanistic model recently postulated for the inhibition of the ligase of Salmonella typhimurium by phosphinic acids.