1-乙酰氨基乙基膦酸 | 132685-14-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 中文名称: 1-乙酰氨基乙基膦酸
• 英文名称: 1-(N-acetylamino)ethylphosphonic acid
• 英文别名: N-acetyl-1-aminoethylphosphonic acid；1-acetylaminoethylphosphonic acid；Ac-1-AEP；(1-Acetamidoethyl)phosphonic acid；1-acetamidoethylphosphonic acid
• CAS: 132685-14-4
• 化学式: C₄H₁₀NO₄P
• 分子量: 167.101
• InChiKey: OWNNFWRGXJDEEX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  86.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-乙酰氨基乙基膦酸 在 水 作用下， 以 重水 为溶剂， 反应 8.0h， 以23.457%的产率得到
  参考文献：
  名称：

  1-(N-酰基氨基)烷基膦酸——水溶液中的脱酰

  摘要：

  图形摘要摘要 1-(N-酰基氨基)烷基膦酸(AC)-AAP属于令人感兴趣且具有潜在药理学重要性的1-氨基烷基膦酸衍生物组。由于 (AC)-AAP 对水解脱酰的敏感性可以形成影响其生物活性的重要因素，我们在水性介质中对这些化合物进行了脱酰研究。在本文中，我们介绍了各种类型的 1-(N-酰氨基) 烷基膦酸 (AC)-AAP 脱酰的结果，包括 1-(N-乙酰氨基) 烷基-膦酸 Ac-AAP、1-(N-氯乙酰氨基) ）烷基膦酸 Mca-AAP、1-（N-三氟乙酰氨基）烷基膦酸 TFA-AAP 和 1-（N-苯甲酰氨基）-烷基膦酸 Bz-AAP，衍生自代表性 1-氨基烷基膦酸 AAP（GlyP、AlaP、ValP、PglP ,

  DOI：

  10.1080/10426507.2017.1286494
• 作为产物：
  描述：

  (+/-)-1-(acetylamino)-1-dimethylphosphonylethane 在 盐酸 、 水 作用下， 反应 2.0h， 以97%的产率得到1-乙酰氨基乙基膦酸
  参考文献：
  名称：

  Penicillin G acylase-mediated kinetic resolution of racemic 1-( N -acylamino)alkylphosphonic and 1-( N -acylamino)alkylphosphinic acids and their esters

  摘要：

  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.

  DOI：

  10.1016/j.molcatb.2016.05.011

文献信息

• 1-(Acylamino)alkylphosphonic Acids—Alkaline Deacylation
  作者：Marek Cypryk、Jozef Drabowicz、Bartlomiej Gostynski、Marcin Kudzin、Zbigniew Kudzin、Pawel Urbaniak

  DOI：10.3390/molecules23040859

  日期：——

  The alkaline deacylation of a representative series of 1-(acylamino)alkylphosphonic acids [(AC)-AAP: (AC) = Ac, TFA, Bz; AAP = GlyP, AlaP, ValP, PglP and PheP] in an aqueous solution of KOH (2M) was investigated. The results suggested a two-stage reaction mechanism with a quick interaction of the hydroxyl ion on the carbonyl function of the amide R-C(O)-N(H)- group in the first stage, which leads to

  一系列代表性的1-（酰基氨基）烷基膦酸[（AC）-AAP：（AC）= Ac，TFA，Bz; 研究了在KOH（2M）水溶液中的AAP = GlyP，AlaP，ValP，PglP和PheP]。结果表明，在第一阶段中，羟基离子与酰胺RC（O）-N（H）-的羰基官能团具有快速相互作用的两阶段反应机理，导致中间体酰基- RC（O-）2 -N（H）-的羟基加合物，在31P NMR光谱中可见。在第二阶段中，这些中间体通过RC（O-）2 -N（H）-官能的分解而缓慢分解，随后形成1-氨基烷基膦酸酯和羧酸根离子。
• Tritylamine (triphenylmethylamine) in organic synthesis; III. The synthesis of 1-aminoalkylphosphonic acids in the reaction of N-(triphenylmethyl)alkanimines with phosphorus trichloride in acetic acid or with phosphonic acid in acetic anhydride.
  作者：Miroslaw Soroka、Waldemar Goldeman

  DOI：10.3998/ark.5550190.0011.b29

  日期：——

  The reaction of phosphorus trichloride in acetic acid or phosphonic (phosphorous) acid in acetic anhydride, with N-(triphenylmethyl)alkanimines gives 1-acetylaminoalkylphosphonic acids 1a-j, which after hydrolysis give 1-aminoalkylphosphonic acids 2a-j in good yields.

  三氯化磷在乙酸中或在乙酸酐中的膦酸（亚磷酸）与 N-（三苯基甲基）链烷胺反应生成 1-乙酰氨基烷基膦酸 1a-j，水解后生成 1-氨基烷基膦酸 2a-j，收率良好。
• Characterization and structure of DhpI, a phosphonate <i>O</i> -methyltransferase involved in dehydrophos biosynthesis
  作者：Jin-Hee Lee、Brian Bae、Michael Kuemin、Benjamin T. Circello、William W. Metcalf、Satish K. Nair、Wilfred A. van der Donk

  DOI：10.1073/pnas.1006848107

  日期：2010.10.12

  Phosphonate natural products possess a range of biological activities as a consequence of their ability to mimic phosphate esters or tetrahedral intermediates formed in enzymatic reactions involved in carboxyl group metabolism. The dianionic form of these compounds at pH 7 poses a drawback with respect to their ability to mimic carboxylates and tetrahedral intermediates. Microorganisms producing phosphonates have evolved two solutions to overcome this hurdle: biosynthesis of monoanionic phosphinates containing two P-C bonds or esterification of the phosphonate group. The latter solution was first discovered for the antibiotic dehydrophos that contains a methyl ester of a phosphonodehydroalanine group. We report here the expression, purification, substrate scope, and structure of the O -methyltransferase from the dehydrophos biosynthetic gene cluster. The enzyme utilizes S -adenosylmethionine to methylate a variety of phosphonates including 1-hydroxyethylphosphonate, 1,2-dihydroxyethylphosphonate, and acetyl-1-aminoethylphosphonate. Kinetic analysis showed that the best substrates are tripeptides containing as C-terminal residue a phosphonate analog of alanine suggesting the enzyme acts late in the biosynthesis of dehydrophos. These conclusions are corroborated by the X-ray structure that reveals an active site that can accommodate a tripeptide substrate. Furthermore, the structural studies demonstrate a conformational change brought about by substrate or product binding. Interestingly, the enzyme has low substrate specificity and was used to methylate the clinical antibiotic fosfomycin and the antimalaria clinical candidate fosmidomycin, showing its promise for applications in bioengineering.

  膦酸天然产物具有一系列生物活性，这是因为它们能够模拟在羧基代谢中涉及的酶反应中形成的磷酸酯或四面体中间体。这些化合物在pH 7下的二阴离子形式对于模拟羧酸和四面体中间体的能力存在缺陷。产生膦酸的微生物已经演化出两种解决方案来克服这个障碍：合成含有两个P-C键的单阴离子膦酸盐或对膦酸基团进行酯化。后一种解决方案首次发现于含有膦酸脱氢丙氨酸甲酯基团的抗生素脱氢膦。我们在这里报道了脱氢膦生物合成基因簇中的O-甲基转移酶的表达、纯化、底物范围和结构。该酶利用S-腺苷甲硫氨酸对多种膦酸进行甲基化，包括1-羟乙基膦酸、1,2-二羟乙基膦酸和乙酰-1-氨基乙基膦酸。动力学分析表明，最佳底物是三肽，其C-末端残基是丙氨酸的膦酸类似物，这表明该酶在脱氢膦的生物合成过程中起到晚期作用。这些结论得到了X射线结构的证实，揭示了一个可以容纳三肽底物的活性位点。此外，结构研究表明，底物或产物结合引起了构象变化。有趣的是，该酶的底物特异性较低，并且已被用于甲基化临床抗生素磷霉素和抗疟疾临床候选药物磷膜多霉素，显示了其在生物工程应用中的潜力。
• Kudzin, Zbigniew H.; Drabowicz, Jozef; Sochacki, Marek, Phosphorus, Sulfur and Silicon and the Related Elements, 1994, vol. 92, # 1-4, p. 77 - 94
  作者：Kudzin, Zbigniew H.、Drabowicz, Jozef、Sochacki, Marek、Wisniewski, Witold

  DOI：——

  日期：——
• Kudzin; Depczynski; Andrijewski, Polish Journal of Chemistry, 2005, vol. 79, # 3, p. 499 - 513
  作者：Kudzin、Depczynski、Andrijewski、Drabowicz、Luczak

  DOI：——

  日期：——