N-benzyloxycarbonylaminomethyl(P-methyl)phosphinic acid | 154370-37-3

• 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-benzyloxycarbonylaminomethyl(P-methyl)phosphinic acid
• 英文别名: methyl[1-[[(phenylmethoxy)carbonyl]amino]methyl]phosphinic acid；Benzyloxycarbonylaminomethyl-methyl-phosphinic acid；methyl(phenylmethoxycarbonylaminomethyl)phosphinic acid
• CAS: 154370-37-3
• 化学式: C₁₀H₁₄NO₄P
• 分子量: 243.199
• InChiKey: WJYZLHFBKNWWDZ-UHFFFAOYSA-N

物化性质

• 熔点：
  123-125 °C
• 沸点：
  528.2±43.0 °C(Predicted)
• 密度：
  1.285±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-benzyloxycarbonylaminomethyl(P-methyl)phosphinic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 (N-carbobenzoxyaminomethyl)methylphosphinic chloride
  参考文献：
  名称：

  Peptides containing the novel methylphosphinamide transition-state isostere

  摘要：

  A convenient route towards the synthesis of peptides containing the methylphosphinamide moiety as a novel transition-state isostere of the amide bond hydrolysis is described. The key step being the coupling of a methylphosphinic chloride with an amino acid or peptide protected at the C-terminus. A proper choice of the amino protecting group appeared to be essential.

  DOI：

  10.1016/s0040-4020(01)80258-1
• 作为产物：
  描述：

  methyl N-benzyloxycarbonylaminomethyl(P-methyl)phosphinate 在 lithium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 48.0h， 以87%的产率得到N-benzyloxycarbonylaminomethyl(P-methyl)phosphinic acid
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Novel Organophosphorus Inhibitors of Bacterial Ureases

  摘要：

  A new group of organophosphorus inhibitors of urease, P-methyl phosphinic acids was discovered by using the structure based inhibitor design approach. Several derivatives of the lead compound, aminomethyl(P-methyl)phosphinic acid, were synthesized successfully. Their potency was evaluated in vitro against urease from Bacillus pasteurii and Proteus vulgaris. The studied compounds constitute a group of competitive, reversible inhibitors of bacterial ureases. Obtained thiophosphinic analogues of the most effective structures exhibited kinetic characteristics of potent, slow binding urease inhibitors, with K-i = 170 nM (against B. pasteurii enzyme) for the most active N-(N'-benzyloxycarbonylglycyl)aminomethyl(P-methyl)phosphinothioic acid.

  DOI：

  10.1021/jm800570q

文献信息

• A general method for the synthesis of N-protected α-aminoalkylphosphinic acids
  作者：Shoujun Chen、James K. Cowark

  DOI：10.1016/0040-4039(96)00839-8

  日期：1996.6

  A general and highly convenient method for the synthesis of N-protected α-aminophosphinic acids, suitable for side chain elongation either from N-, P-, or C- termini to form a variety of phosphinic peptides, has been developed. The desired phosphinic acids were obtained in moderate to satisfactory yield by a three-component condensation reaction of benzyl carbamate, an aldehyde, and an alkylphosphonous

  已经开发了一种合成N-保护的α-氨基次膦酸的通用且高度方便的方法，该方法适于从N-，P-或C-末端侧链延伸以形成多种次膦酸肽。在非常温和的条件下，通过氨基甲酸苄酯，醛和烷基亚膦酸（或其金刚烷胺​​盐）的三组分缩合反应，可以以中等至令人满意的收率获得所需的次膦酸。
• Investigations on New Strategies for the Facile Synthesis of Polyfunctionalized Phosphinates:  Phosphinopeptide Analogues of Glutathionylspermidine
  作者：Shoujun Chen、James K. Coward

  DOI：10.1021/jo971318l

  日期：1998.2.1

  Three possible methods for the facile synthesis of functionalized phosphinates, including the core of complex phosphinopeptide analogues of glutathionylspermidine, were explored. Among these methods, the three-component condensation reaction involving benzyl carbamate, an aldehyde, and a functionalized or nonfunctionalized phosphonite can afford a variety of protected alpha-aminophosphinates. However

  探索了三种轻松合成功能化次膦酸酯的方法，包括谷胱甘肽亚精胺的复杂次膦肽类似物的核心。在这些方法中，涉及氨基甲酸苄酯，醛和官能化或非官能化亚膦酸酯的三组分缩合反应可得到多种保护的α-氨基次膦酸酯。然而，仅通过含多胺的亚膦酸酯与源自三苯胺的席夫碱的酸催化的Pudovik-Abramov-型反应可得到含多胺的α-（氨基亚甲基）次膦酸酯。因此，尽管具有水解稳定性，但Tfa保护的含多胺的亚膦酸酯可与三苯甲基甲亚胺平稳反应，并提供相应的次膦酸酯，合成谷胱甘肽亚精胺合成酶的膦肽肽抑制剂的关键中间体。通过选择性脱保护并偶联至受保护的二肽来精制该中间体，提供了谷胱甘肽亚精胺的含丙氨酸的次膦酸酯类似物。讨论了三种探索方法的局限性和范围。
• Novel inhibitors of trypanothione biosynthesis: Synthesis and evaluation of a phosphinate analog of glutathionyl spermidine (GSP), a potent, slow-binding inhibitor of GSP synthetase
  作者：Shoujun Chen、Chun-Hung Lin、Christopher T. Walsh、James K. Coward

  DOI：10.1016/s0960-894x(97)00061-9

  日期：1997.3
• US4374131A
  申请人：——

  公开号：US4374131A

  公开（公告）日：1983-02-15
• Design, Synthesis, and Evaluation of Novel Organophosphorus Inhibitors of Bacterial Ureases
  作者：Stamatia Vassiliou、Agnieszka Grabowiecka、Paulina Kosikowska、Athanasios Yiotakis、Paweł Kafarski、Łukasz Berlicki

  DOI：10.1021/jm800570q

  日期：2008.9.25

  A new group of organophosphorus inhibitors of urease, P-methyl phosphinic acids was discovered by using the structure based inhibitor design approach. Several derivatives of the lead compound, aminomethyl(P-methyl)phosphinic acid, were synthesized successfully. Their potency was evaluated in vitro against urease from Bacillus pasteurii and Proteus vulgaris. The studied compounds constitute a group of competitive, reversible inhibitors of bacterial ureases. Obtained thiophosphinic analogues of the most effective structures exhibited kinetic characteristics of potent, slow binding urease inhibitors, with K-i = 170 nM (against B. pasteurii enzyme) for the most active N-(N'-benzyloxycarbonylglycyl)aminomethyl(P-methyl)phosphinothioic acid.