(1-(benzyloxycarbonylamino)ethyl)methylphosphinic acid

• 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: (1-(benzyloxycarbonylamino)ethyl)methylphosphinic acid
• 英文别名: 1-(benzyloxycarbonylamino)ethyl(methyl)phosphinic acid；1-(benzyloxycarbonylamino)ethylmethylphosphinic acid；Methyl [1-[[(phenylmethoxy)carbonyl]amino]ethyl]phosphinic acid；methyl-[1-(phenylmethoxycarbonylamino)ethyl]phosphinic acid
• 化学式: C₁₁H₁₆NO₄P
• 分子量: 257.226
• InChiKey: GWKJZVKDYTZYQR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 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：

  乙醇 、 (1-(benzyloxycarbonylamino)ethyl)methylphosphinic acid 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以68%的产率得到ethyl <1-((benzyloxycarbonyl)amino)ethyl>methylphosphinate
  参考文献：
  名称：

  Synthesis of novel N-phosphonoalkyl dipeptide inhibitors of human collagenase

  摘要：

  The synthesis of a series of N-phosphonoalkyl dipeptides 6 is described. Syntheses were devised that allowed the preparation of single diastereoisomers and the assignment of stereochemistry. The compounds were evaluated in vitro for their ability to inhibit the degradation of radiolabeled collagen by purified human lung fibroblast collagenase. Several of the compounds were potent collagenase inhibitors and were at least l0-fold more potent than their corresponding N-carboxyalkyl analogues. Activity was lost when the phosphonic acid group P(O)(OH)(2) was replaced by the phosphinic acid groups P(O)(H)(OH) and P(O)(Me)(OH). At the P-1 position, (R)- or (S)-allkyl groups, especially ethyl and methyl (e.g., 12a,b, 52a,b, and 53a,b), or an (R)-phenethyl moiety (55a) conferred high potency (IC50 values in the range 0.23-0.47 mu M). (S)-Stereochemistry was preferred for the P-1(') isobutyl side chain. Structure-activity relationships were also investigated at the P-2(') site, and interestingly, compounds with basic side chains such as the guanidine 57a, were equipotent with more lipophilic compounds, such as 52a. As with other series of collagenase inhibitors, potency was enhanced by introducing bicyclic aromatic P-2(') substituents. The most potent phosphonic acid of the series was the bicyclic aromatic P-2(') tryptophan analogue 59a (IC50 0.05 mu M).

  DOI：

  10.1021/jm00027a020
• 作为产物：
  描述：

  氨基甲酸苄酯 在 乙酸酐 、 三氟乙酸 作用下， 生成 (1-(benzyloxycarbonylamino)ethyl)methylphosphinic acid
  参考文献：
  名称：

  氢磷酰基化合物的酰胺烷基化

  摘要：

  作为构建假α，α′-二肽分子的α-氨基磷酰基片段的简便方法，开发了一种新的温和的氢化磷酰基化合物在乙酸酐和乙酰氯混合物中的酰胺基烷基化的方法。反应中间体N，N′-亚苄基-和N，N检测，分离和鉴定了'-亚烷基双氨基甲酸酯。该报告提供了以下结果：研究了先前与双氨基甲酸酯合成的氢磷酰基化合物在乙酸酐和其他溶剂中的直接相互作用，磷组分和双甲酸氨基甲酸酯的结构的影响以及酸催化对该双组分反应过程的影响。 。提出了氢磷酰基化合物酰胺烷基烷基化三组分反应机理的新形式：它被认为是一个多阶段过程，涉及到双甲氨基甲酸酯的形成阶段，然后是Arbuzov型反应阶段，中间形成酰基亚胺基阳离子和具有三价磷的P-OAc衍生物。

  DOI：

  10.1134/s1070363211060041

文献信息

• Arbuzov-type reaction of acylphosphonites and N-alkoxycarbonylimine cations generated in situ with trifluoroacetic anhydride
  作者：Maxim E. Dmitriev、Valery V. Ragulin

  DOI：10.1016/j.tetlet.2012.01.094

  日期：2012.3

  N-protected α-aminoalkylphosphinic acids by the reaction of N,N′-benzylidene- or N,N′-alkylidenebiscarbamates, trifluoroacetic anhydride and the corresponding alkylphosphonous acids in methylene chloride or toluene is described. The results obtained confirm the earlier proposed mechanism for amidoalkylation of hydrophosphorylic compounds involving an Arbuzov-type reaction step.

  描述了通过N，N'-亚苄基-或N，N'-亚烷基双氨基甲酸酯，三氟乙酸酐和相应的烷基亚膦酸在二氯甲烷或甲苯中反应合成N-保护的α-氨基烷基次膦酸的温和方法。获得的结果证实了较早提出的涉及Arbuzov型反应步骤的氢磷酸化合物酰胺烷基化的机理。
• Amino and substituted amino phosphinylalkanoyl compounds
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04416831A1

  公开（公告）日：1983-11-22

  Compounds of the formula ##STR1## wherein X is an imino acid or ester and R.sub.1 is hydrogen, ##STR2## are useful hypotensive agents due to their angiotensin converting enzyme inhibition activity.

  式子为##STR1##的化合物，其中X是亚氨基酸或酯，R.sub.1是氢，##STR2##，由于其抑制血管紧张素转化酶的活性，因此是有用的降压剂。
• Amino and substituted amino phosphinyl-alkanoyl compounds
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04374131A1

  公开（公告）日：1983-02-15

  Compounds of the formula ##STR1## wherein X is an imino acid or ester and R.sub.1 is hydrogen, ##STR2## are useful hypotensive agents due to their angiotensin converting enzyme inhibition activity.

  式为##STR1##的化合物中，其中X是亚氨基酸或酯，R.sub.1是氢，##STR2##是由于它们的血管紧张素转换酶抑制活性而有用的降压剂。
• Amino and substituted amino phosphinyl-alkanoyl compositions
  申请人：E.R. Squibb & Sons, Inc.

  公开号：EP0063896A1

  公开（公告）日：1982-11-03

  Compounds of the formula wherein X Is an imino acid or ester and R, is hydrogen. are useful hypotensive agents due to their angiotensin converting enzyme inhibition activity.

  式中的化合物 其中 X 为亚胺酸或酯，R 为氢。 由于具有血管紧张素转换酶抑制活性，因此是有用的降血压药物。
• Acyloxy derivatives of trivalent phosphorus in amidoalkylation of hydrophosphoryl compounds
  作者：M. E. Dmitriev、V. V. Ragulin

  DOI：10.1134/s1070363213100150

  日期：2013.10

  In order to model the previously suggested mechanism of the P-C bond formation via the Arbuzov reaction, we have studied the interaction of diethylacylphosphite (prepared beforehand as well as generated in situ from tetraethylpyrophosphite) with the in situ generated acyliminium cation. Various conditions of in situ generation of acylphosphite derivatives of P(III) from hydrophosphoryl compounds and acyliminium ions from N,N'-alkylidenebiscarbamates have been investigated: solvent nature, acid catalyst, and the reagents mixing order). The results obtained have confirmed the suggested mechanism of three-component reaction of amidoalkylation of hydrophosphoryl compounds with the formation of P-C bond via the Arbuzov reaction of in situ formed intermediates.