1-R-1-[(N-benzyloxycarbonyl-L-alanyl)amino]ethanephosphonic acid | 60668-26-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1-R-1-[(N-benzyloxycarbonyl-L-alanyl)amino]ethanephosphonic acid
• 英文别名: (1R)-1-[(N-benzyloxycarbonyl-L-alanyl)amino]-ethylphosphonic acid；[(1R)-1-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]ethyl]phosphonic acid
• CAS: 60668-26-0
• 化学式: C₁₃H₁₉N₂O₆P
• 分子量: 330.277
• InChiKey: WYEJTGPPLZWRGJ-VHSXEESVSA-N

物化性质

• 密度：
  1.359±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  125
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-R-1-[(N-benzyloxycarbonyl-L-alanyl)amino]ethanephosphonic acid 在 氢溴酸 、 溶剂黄146 、 三乙胺 、 methyloxirane 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 amino>ethyl>phosphonic acid
  参考文献：
  名称：

  Synthesis and structure-activity relationships of antibacterial phosphonopeptides incorporating (1-aminoethyl)phosphonic acid and (aminomethyl)phosphonic acid

  摘要：

  Phosphonodipeptides and phosphonooligopeptides based on L- and D-(1-aminoethyl)phosphonic acids L-Ala(P) and D-Ala(P) and (aminomethyl)phosphonic acid Gly(P) at the acid terminus have been synthesized and investigated as antibacterial agents, which owe their activity to the inhibition of bacterial cell-wall biosynthesis. A method for large-scale synthesis of the potent antibacterial agent L-Ala-L-Ala(P) (1, Alafosfalin) is described. Structure-activity relationships in the dipeptide series have been studied by systematic variation of structure 1. L stereochemistry is generally required for both components. Changes in the L-Ala(P) moiety mostly lead to loss of antibacterial activity, but the phosphonate analogues of L-phenylalanine, L-Phe(P), and L-serine, L-Ser(P), give rise to weakly active L-Ala-L-Phe(P) and L-Ala-L-Ser(P). Replacement of L-Ala in 1 by common and rare amino acids can give rise to more potent in vitro antibacterials such as L-Nva-L-Ala(P) (45). Synthetic variation of these more potent dipeptides leads to decreased activity. Phosphonooligopeptides such as (L-Ala)2-L-Ala(P) have a broader in vitro antibacterial spectrum than their phosphonodipeptide precursor, but this is not expressed in vivo, presumably due to rapid metabolism to 1. Stabilized compounds such as Sar-L-Nva-L-Nva-L-Ala(P) (46) have been developed that are more potent in vivo and have a broader in vivo antibacterial spectrum than the parent phosphonodipeptide.

  DOI：

  10.1021/jm00151a005
• 作为产物：
  描述：

  苄氧羰基-L-丙氨酸 在 三乙胺 作用下， 以 乙酸乙酯 为溶剂， 反应 0.5h， 生成 1-R-1-[(N-benzyloxycarbonyl-L-alanyl)amino]ethanephosphonic acid
  参考文献：
  名称：

  Preparation of N-Acylated Phosphonopeptides with Free Phosphonic Group

  摘要：

  Aminoalkylphosphonic acids on heating with hexamethyldisilazane yield tris(trimethylsilyl) derivatives, which are used as amino components for the synthesis of N-acylated phosphonopeptides with free phosphonic group. These transformations proceed with complete retention of the stereoconfiguration of aminophosphonate moiety.

  DOI：

  10.1080/00397919108021063

文献信息

• Chemical process for the production of .alpha.-aminophosphonic acids and
  申请人：Ciba-Geigy Corporation

  公开号：US04331591A1

  公开（公告）日：1982-05-25

  The present invention provides a process for the production of physiologically-useful .alpha.-aminophosphonic acids and peptide derivatives of the formula: ##STR1## wherein R and R.sub.1 may be the same or different and each can be hydrogen, deuterium or an optionally substituted lower alkyl group, lower alkenyl, lower alkynyl, cycloalkyl, aryl or heterocyclic radical containing one or more oxygen, nitrogen or sulphur atoms and which may be fused to an aromatic ring, a lower alkyl group substituted by a cycloalkyl radical, a lower alkyl group substituted by an aryl radical, a lower alkyl group substituted by a heterocyclic radical as defined above or R and R.sub.1 together form a polymethylene chain optionally interrupted by an oxygen, nitrogen or sulphur atom, or R.sub.1 represents, together with the C(R)--N< residue to which it is attached, the atoms required to complete a heterocyclic radical; and R.sub.2 can be hydrogen, optionally substituted lower alkyl, cycloalkyl, aryl or lower alkyl substituted by a cycloalkyl radical, lower alkyl substituted by a heterocyclic radical containing one or more nitrogen atoms; by a heterocyclic radical containing one or more nitrogen atoms, or R.sub.2 together with the C(H)--N residue to which it is attached, may represent the atoms required to complete a heterocyclic radical; and n is 0, 1, 2, 3 or 4; comprising oxidizing, using an oxidizing agent, a compound having the formula: ##STR2## wherein R, R.sup.1, R.sup.2 and n have their previous significance, and Z is H or a protecting group usually used for an amino group; and then removing any protecting group.

  本发明提供了一种制备生理有用的α-氨基膦酸和肽衍生物的方法，其化学式为：##STR1## 其中R和R.sub.1可以相同也可以不同，每个可以是氢、氘或者是一个含有一个或多个氧、氮或硫原子的可选取代的较低烷基、较低烯基、较低炔基、环烷基、芳基或杂环基，并且可以与芳香环融合，可以是一个由环烷基取代的较低烷基，可以是一个由芳基取代的较低烷基，可以是一个由上述定义的杂环基取代的较低烷基，或者R和R.sub.1一起形成一个可以由氧、氮或硫原子中断的聚甲基链，或者R.sub.1表示与其连接的C(R)--N<残基一起，需要完成一个杂环基的原子；R.sub.2可以是氢、可选取代的较低烷基、环烷基、芳基或者由环烷基取代的较低烷基、由含有一个或多个氮原子的杂环基取代的较低烷基，或者是由含有一个或多个氮原子的杂环基取代的较低烷基，或者R.sub.2与其连接的C(H)--N残基一起，可以表示需要完成一个杂环基的原子；n为0、1、2、3或4。该方法包括使用氧化剂氧化化合物，该化合物的化学式为：##STR2## 其中R、R.sup.1、R.sup.2和n具有其前述的意义，Z为H或通常用于氨基的保护基；然后去除任何保护基。
• Use of the dehydrophos biosynthetic enzymes to prepare antimicrobial analogs of alaphosphin
  作者：Despina J. Bougioukou、Chi P. Ting、Spencer C. Peck、Subha Mukherjee、Wilfred A. van der Donk

  DOI：10.1039/c8ob02860e

  日期：——

  enzyme is also tolerant with respect to the amino acid attached to tRNALeu. Using a mutant of leucyl tRNA synthetase that is deficient in its proofreading ability allowed the preparation of a series of aminoacyl-tRNALeu derivatives (Ile, Ala, Val, Met, norvaline, and norleucine). DhpH-C accepted these aminoacyl-tRNA derivatives and condensed the amino acid with l-Ala(P) to form the corresponding phosphonodipeptides

  脱磷生物合成酶DhpH（DhpH-C）的C末端结构域催化Leu-tRNALeu与（R）-1-氨基乙基膦酸酯（丙氨酸的氨基膦酸酯类似物Ala（P））缩合。该反应的产物Leu-Ala（P）是磷酸二肽，一类化合物，以前已被研究用作临床抗生素。在这项研究中，我们表明DhpH-C具有高度的底物耐受性，并且可以将各种氨基膦酸酯（Gly（P），Ser（P），Val（P），1-氨基-丙基膦酸酯和苯基甘氨酸（P））缩合到Leu。而且，该酶对tRNALeu上连接的氨基酸也具有耐受性。使用缺乏校对能力的亮氨酰tRNA合成酶突变体，可以制备一系列氨酰基-tRNALeu衍生物（Ile，Ala，Val，Met，正缬氨酸和正亮氨酸）。DhpH-C接受这些氨基酰基-tRNA衍生物，并将氨基酸与1-Ala（P）缩合形成相应的磷酸二肽。这些肽的一部分显示出抗微生物活性，表明该酶是制备抗微生物肽的通用生物催化剂。我们还研究了来
• Peptide derivatives of phosphonic and phosphinic acids and intermediates
  申请人：Hoffmann-La Roche Inc.

  公开号：US04016148A1

  公开（公告）日：1977-04-05

  The present disclosure relates to peptide derivatives. More particularly, the disclosure is concerned with peptide derivatives of phosphonic and phosphinic acids, a process for the manufacture thereof and pharmaceutical preparations containing same.

  本公开涉及肽衍生物。更具体地，涉及磷酸和亚磷酸的肽衍生物，其制造过程以及含有它们的制药制剂。
• Compositions having antibiotic properties
  申请人：Hoffmann-La Roche Inc.

  公开号：US04100275A1

  公开（公告）日：1978-07-11

  Compositions having antibiotic properties containing as antibiotic potentiators peptides of the formula ##STR1## wherein R.sup.1 represents a hydrogen atom or a lower alkyl, lower cycloalkyl, (lower cycloalkyl)-(lower alkyl), aryl or aryl(lower alkyl) group (said group being optionally substituted as the case may require by one or more amino, hydroxy, thio, methylthio, carboxy or guanidino groups so as to form the characterizing group of a naturally occurring L .alpha.-amino acid); R.sup.2 and R.sup.3 each represent the characterizing group of an .alpha.-amino acid of the type normally found in proteins with the proviso that R.sup.3 cannot represent a hydrogen atom when n is zero and R.sup.1 is a hydrogen atom or the phenyl group; R.sup.4 represents a hydroxy or methyl group; n stands for zero, 1, 2 or 3; and single asterisks denote that the configuration at the carbon atom so-marked is L when R.sup.2 or R.sup.3 as the case may be represents other than a hydrogen atom; and the double asterisk denotes that, when R.sup.1 represents other than a hydrogen atom, the configuration at the carbon atom so-marked is (R) (as hereinafter defined), And an antibiotic are disclosed.

  本发明涉及具有抗生素性质的组合物，其中包含抗生素增效剂的肽，其化学式为##STR1##其中R.sup.1表示氢原子或较低的烷基，较低的环烷基，（较低的环烷基）-（较低的烷基），芳基或芳基（较低的烷基）基团（所述基团根据需要可以由一个或多个氨基，羟基，硫醇基，甲硫基，羧基或鸟氨酸基团取代，以形成天然存在的L.α.-氨基酸的表征基团）; R.sup.2和R.sup.3各代表通常在蛋白质中发现的α-氨基酸的表征基团，但是当n为零且R.sup.1为氢原子或苯基时，R.sup.3不能代表氢原子; R.sup.4表示羟基或甲基基团; n代表零，1，2或3; 单个星号表示所标记的碳原子的构型为L，当R.sup.2或R.sup.3代表除氢原子以外的其他原子时; 双星号表示当R.sup.1代表除氢原子以外的其他原子时，所标记的碳原子的构型为（R）（如下所定义），并且公开了一种抗生素。
• Process for influencing plant growth
  申请人：CIBA-GEIGY AG

  公开号：EP0010067A2

  公开（公告）日：1980-04-16

  An agent for influencing plant growth, in particular a herbicidal and plant growth inhibiting agent, contains, in addition to carriers and/or other additives, at least one compound of the formula:- or the corresponding zwitterion form in which R and R1 may be the same or different and each can be hydrogen, deuterium or an optionally substituted lower alkyl group, lower alkenyl, lower alkynyl, cycloalkyl, aryl or heterocyclic radical containing one or more oxygen, nitrogen or sulphur atoms and which may be fused to an aromatic ring, a lower alkyl group substituted by a cycloalkyl radical, a lower alkyl group substituted by an aryl radical, a lower alkyl group substituted by a heterocyclic radical as defined above, or R and R together form a polymethylene chain optionally interrupted by an oxygen, nitrogen or sulphur atoms, or R represents, together with the C(R)-N < residue to which it is attached, the atoms required to complete a heterocyclic radical; and R2 and R3 may be the same or different and each can be hydrogen, optionally substituted lower alkyl, cycloalkyl, aryl or lower alkyl substituted by a heterocyclic radical containing one or more nitrogen atom; a heterocyclic radical containing one or more nitrogen atoms; or R2 and R3, independently, together with the C(H)-N residue to which each is attached, may each represent the atoms required to complete a heterocyclic radical; R. is OH CH3; or phenyl; R7 is hydrogen or an alkoxycarbonyl or benzyloxycarbonyl group; and n is 0, 1, 2 or 3; as well as the esters or partial esters thereof with physiologically splittable alcohols; salts of the compounds of formula I, or their esters or partial esters with acids or bases physiologically acceptable to plants, respectively; and all optical isomers thereof.

  一种影响植物生长的制剂，特别是一种除草剂和植物生长抑制剂，除载体和/或其他添加剂外，还含有至少一种式如下的化合物 或相应的齐聚物形式，其中 R 和 R1 可以相同或不同，并且各自可以是氢、氘或任选取代的低级烷基、低级烯基、低级炔基、环烷基、芳基或杂环基，这些基团含有一个或多个氧原子、氮原子或硫原子，并可与芳香环融合；被环烷基取代的低级烷基、被芳基取代的低级烷基、被上文定义的杂环基取代的低级烷基，或 R 和 R 共同形成可选择被氧、氮或硫原子打断的多亚甲基链，或 R 与所连接的 C(R)-N < 残基一起代表完成杂环基所需的原子；和 R2 和 R3 可以相同或不同，各自可以是氢、任选取代的低级烷基、环烷基、芳基或被含一个或多个氮原子的杂环基取代的低级烷基；含一个或多个氮原子的杂环基；或 R2 和 R3 与各自所连接的 C(H)-N 残基一起独立地各自代表完成一个杂环基所需的原子；R.是 OH CH3；或苯基；R7 是氢或烷氧羰基或苄氧羰基；n 是 0、1、2 或 3；以及其与生理上可拆分的醇的酯或部分酯；式 I 化合物或其酯或部分酯分别与植物生理上可接受的酸或碱的盐，以及其所有光学异构体。