N-Benzyloxycarbonyl-α-aminopropylphosphonsaeure | 61937-83-5

• 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-Benzyloxycarbonyl-α-aminopropylphosphonsaeure
• 英文别名: 1-(Phenylmethoxycarbonylamino)propylphosphonic acid
• CAS: 61937-83-5
• 化学式: C₁₁H₁₆NO₅P
• 分子量: 273.226
• InChiKey: LEECCTMGELXXIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 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：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  甲醇 、 N-Benzyloxycarbonyl-α-aminopropylphosphonsaeure 在 吡啶 、 三氯乙腈 作用下， 生成 methyl 1-(benzyloxycarbonylamino)propyl phosphonate
  参考文献：
  名称：

  Wasielewski,C. et al., Roczniki Chemii, 1976, vol. 50, p. 1613 - 1620

  摘要：

  DOI：

文献信息

• Derivatives of 1-aminoalkylphosphonate diaryl esters, method of 1-aminoalkylphosphonate diaryl ester derivatives preparation and their application
  申请人：Universität Ulm

  公开号：EP2676962A1

  公开（公告）日：2013-12-25

  The subject of the invention relates to 1-aminoalkylphosphonate diaryl esters of formula I, in which Bt represents biotin, W is a hydrocarbon linker chain of 5 to 10 carbon atoms, Y is the amino acid residues in an amount of 0 to 4, R is a substituent corresponding to the side chain of valine, alanine, leucine, phenylalanine, 4-guanidinephenylglycine, or 2-aminobutyric acid (Abu), X is the hydrogen or a compound selected from the group consisting of mercaptomethyl (S-methyl), methoxy (O-methyl), or carboxymethyl, and their use as inhibitors of serine proteases, and the low molecular weight molecular probes to detect the catalytically active forms of the enzymes. A process for preparing 1-aminoalkylphosphonate diaryl esters of formula I, in which Bt represents biotin, W is a hydrocarbon linker chain of 5 to 10 carbon atoms, Y is the amino acid residues in an amount of 0 to 4, R is a substituent corresponding to the side chain of valine, alanine, leucine, phenylalanine, 4-guanidinephenylglycine, or 2-aminobutyric acid (Abu), X is the hydrogen or a compound selected from the group consisting of mercaptomethyl (S-methyl), methoxy (O-methyl), or carboxymethyl relies on application of triaryl phosphite, obtained from the phenol substituted at para position phosphorus (III) chloride in refluxing acetonitrile and is subjected to amidoalkylation reaction with benzyl carbamate and an aldehyde such as acetaldehyde, propionic aldehyde, iso-butyric aldehyde, phenylacetic aldehyde, p-nitrobenzoic aldehyde and isovaleric aldehyde, followed by the synthesis of hydrobromide salts of 1-aminoalkylphosphonate diaryl esters, in which the benzyloxycarbonyl (Cbz) protective group is removed, and in the next step is reacted with an amino acid containing protected α-amino group in the presence of a coupling reagent. The resulting phosphonic dipeptide containing tert-butoxycarbonyl (t-Boc) protective group is subjected to deprotection of α-amino group and obtained dipeptidyl 1-aminoalkylphosphonate diaryl ester is coupled with another amino acid with protected α-amino group, biotin or a derivative thereof in a manner analogous to that described above.

  本发明的主题涉及式 I 的 1-氨基烷基膦酸二芳基酯，其中 Bt 代表生物素，W 是 5 至 10 个碳原子的烃连接链，Y 是量为 0 至 4 的氨基酸残基，R 是对应于缬氨酸、丙氨酸、亮氨酸、苯丙氨酸侧链的取代基、4-胍基苯甘氨酸或 2-氨基丁酸（Abu），X 是氢或选自巯甲基（S-甲基）、甲氧基（O-甲基）或羧甲基组成的组的化合物，以及它们作为丝氨酸蛋白酶抑制剂和检测酶的催化活性形式的低分子量分子探针的用途。 一种制备式 I 的 1-氨基烷基膦酸二芳基酯的工艺，其中 Bt 代表生物素，W 是 5 至 10 个碳原子的烃连接链，Y 是氨基酸残基，数量为 0 至 4，R 是与缬氨酸侧链相对应的取代基、X 是氢或选自巯基甲基（S-甲基）、甲氧基甲基（O-甲基）或羧基甲基组成的化合物、在回流的乙腈中加入在对位被磷 (III) 氯化物取代的苯酚，然后与氨基甲酸苄酯和醛如乙醛、丙醛、异丁醛、苯乙酸醛、对硝基苯甲酸醛和异戊醛进行氨基烷基化反应、然后合成 1-氨基烷基膦酸二芳基酯的氢溴酸盐，去掉其中的苄氧羰基（Cbz）保护基，下一步在偶联试剂存在下与含有受保护 α-氨基的氨基酸反应。将得到的含有叔丁氧羰基（t-Boc）保护基的膦酰二肽进行 α-氨基的脱保护处理，然后将得到的 1-氨基烷基膦酸二芳基二肽酯与另一种含有受保护 α-氨基基的氨基酸、生物素或其衍生物以类似上述的方式偶联。
• Wasielewski,C. et al., Roczniki Chemii, 1976, vol. 50, p. 1613 - 1620
  作者：Wasielewski,C. et al.

  DOI：——

  日期：——
• HOFFMANN M., SYNTHESIS,(1986) N 7, 557-559
  作者：HOFFMANN M.

  DOI：——

  日期：——
• A Convenient Synthesis of Alkyl Hydrogen 1-(Benzyloxycarbonylamino)-alkanephosphonates
  作者：Maria Hoffmann

  DOI：10.1055/s-1986-31701

  日期：——