dibenzyl (R)-2-methyl-1-[({4-[(E)-2-(4-methoxyphenyl)vinyl]phenyl}sulfonyl)amino]propylphosphonate | 925463-35-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: dibenzyl (R)-2-methyl-1-[({4-[(E)-2-(4-methoxyphenyl)vinyl]phenyl}sulfonyl)amino]propylphosphonate
• CAS: 925463-35-0
• 化学式: C₃₃H₃₆NO₆PS
• 分子量: 605.692
• InChiKey: WYODOVDZUUQDQS-OBAHAGDOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.75
• 重原子数：
  42.0
• 可旋转键数：
  14.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  90.93
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  dibenzyl (R)-2-methyl-1-[({4-[(E)-2-(4-methoxyphenyl)vinyl]phenyl}sulfonyl)amino]propylphosphonate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 ((R)-1-{4-[2-(4-methoxy-phenyl)-ethyl]-benzenesulfonylamino}-2-methyl-propyl)-phosphonic acid
  参考文献：
  名称：

  α-Biphenylsulfonylamino 2-methylpropyl phosphonates: Enantioselective synthesis and selective inhibition of MMPs

  摘要：

  (R)-alpha-Biphenyisulfonylamino 2-methylpropyl phosphonates attain nM potency against several MMPs and are the most effective inhibitors based on phosphonate as zinc binding group. Since their preparation by direct N-acylation of expensive, enantiopure, alpha-aminophosphonic acids proceeds in low yields, we devised and evaluated a stereoselective and straightforward method of synthesis that avoids the unfavourable step of N-acylation. The key intermediate (R)-4-bromophenylsulfonylamino 2-methylpropyl phosphonate 9 was obtained by highly stereoselective addition of dibenzylphosphite to the enantiopure (S)-N-isobutylidene-p-bromobenzenesulfinamide 3, followed by oxidation with m-CPBA. Suzuki coupling of 9 with the desired arylboronic acids, gave the expected biphenylsulfonylamino derivatives in satisfactory yields. Liberation of the phosphonic group by hydrogenolysis led to the desired (R)-alpha-biphenylsulfonylamino 2-methylpropyl phosphonates 14a-i. Screening of the new compounds on MMP-1, -2, -3, -7, -8, -9, -13 and -14 showed IC50 in the range of nM in most cases. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.10.047
• 作为产物：
  描述：

  dibenzyl (SS,R)-N-(p-bromobenzenesulfinyl)-2-amino-2-methylpropylphosphonate 在 四(三苯基膦)钯 potassium phosphate 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 18.5h， 生成 dibenzyl (R)-2-methyl-1-[({4-[(E)-2-(4-methoxyphenyl)vinyl]phenyl}sulfonyl)amino]propylphosphonate
  参考文献：
  名称：

  α-Biphenylsulfonylamino 2-methylpropyl phosphonates: Enantioselective synthesis and selective inhibition of MMPs

  摘要：

  (R)-alpha-Biphenyisulfonylamino 2-methylpropyl phosphonates attain nM potency against several MMPs and are the most effective inhibitors based on phosphonate as zinc binding group. Since their preparation by direct N-acylation of expensive, enantiopure, alpha-aminophosphonic acids proceeds in low yields, we devised and evaluated a stereoselective and straightforward method of synthesis that avoids the unfavourable step of N-acylation. The key intermediate (R)-4-bromophenylsulfonylamino 2-methylpropyl phosphonate 9 was obtained by highly stereoselective addition of dibenzylphosphite to the enantiopure (S)-N-isobutylidene-p-bromobenzenesulfinamide 3, followed by oxidation with m-CPBA. Suzuki coupling of 9 with the desired arylboronic acids, gave the expected biphenylsulfonylamino derivatives in satisfactory yields. Liberation of the phosphonic group by hydrogenolysis led to the desired (R)-alpha-biphenylsulfonylamino 2-methylpropyl phosphonates 14a-i. Screening of the new compounds on MMP-1, -2, -3, -7, -8, -9, -13 and -14 showed IC50 in the range of nM in most cases. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.10.047