dibenzyl ((2R,3S,4S,5R)-3,4-dihydroxyhexane-2,5-diyl)dicarbamate | 177283-74-8

• 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: dibenzyl ((2R,3S,4S,5R)-3,4-dihydroxyhexane-2,5-diyl)dicarbamate
• 英文别名: benzyl N-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(phenylmethoxycarbonylamino)hexan-2-yl]carbamate
• CAS: 177283-74-8
• 化学式: C₂₂H₂₈N₂O₆
• 分子量: 416.474
• InChiKey: FVAVBFPFMATPGB-YKCBXCCJSA-N

物化性质

• 熔点：
  170-173 °C(Solv: hexane (110-54-3); tetrahydrofuran (109-99-9))
• 沸点：
  647.5±55.0 °C(Predicted)
• 密度：
  1.239±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  117
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  dibenzyl ((2R,3S,4S,5R)-3,4-dihydroxyhexane-2,5-diyl)dicarbamate 在 palladium dihydroxide 盐酸 、 sodium hydride 、 N,N-二异丙基乙胺 、 环己烯 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 90.0h， 生成 (4R,5S,6S,7R)-1,3-Dibenzyl-5,6-dihydroxy-4,7-dimethyl-[1,3]diazepan-2-one
  参考文献：
  名称：

  Preparation and Structure−Activity Relationship of Novel P1/P1‘-Substituted Cyclic Urea-Based Human Immunodeficiency Virus Type-1 Protease Inhibitors

  摘要：

  A series of novel P1/P1'-substituted cyclic urea-based HIV-1 protease inhibitors was prepared. Three different synthetic schemes were used to assemble these compounds. The first approach uses amino acid-based starting materials and was originally used to prepare DMP 323. The other two approaches use L-tartaric acid or L-mannitol as the starting material. The required four contiguous R,S,S,R centers of the cyclic urea scaffold are introduced using substrate control methodology. Each approach has specific advantages based on the desired P1/P1' substituent. Designing analogs based on the enzyme's natural substrates provided compounds with reduced activity. Attempts at exploiting hydrogen bond sites in the S1/S1' pocket, suggested by molecular modeling studies, were not fruitful. Several analogs had better binding affinity compared to our initial leads. Modulating the compound's physical properties led to a 10-fold improvement in translation resulting in better overall antiviral activity.

  DOI：

  10.1021/jm960083n
• 作为产物：
  描述：

  N-[(1R)-1-[甲氧基(甲基)氨基甲酰基]乙基]氨基甲酸苄酯 在 lithium aluminium tetrahydride 、 [VCl3(thf)3] 、 铜 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 dibenzyl ((2R,3S,4S,5R)-3,4-dihydroxyhexane-2,5-diyl)dicarbamate
  参考文献：
  名称：

  Preparation and Structure−Activity Relationship of Novel P1/P1‘-Substituted Cyclic Urea-Based Human Immunodeficiency Virus Type-1 Protease Inhibitors

  摘要：

  A series of novel P1/P1'-substituted cyclic urea-based HIV-1 protease inhibitors was prepared. Three different synthetic schemes were used to assemble these compounds. The first approach uses amino acid-based starting materials and was originally used to prepare DMP 323. The other two approaches use L-tartaric acid or L-mannitol as the starting material. The required four contiguous R,S,S,R centers of the cyclic urea scaffold are introduced using substrate control methodology. Each approach has specific advantages based on the desired P1/P1' substituent. Designing analogs based on the enzyme's natural substrates provided compounds with reduced activity. Attempts at exploiting hydrogen bond sites in the S1/S1' pocket, suggested by molecular modeling studies, were not fruitful. Several analogs had better binding affinity compared to our initial leads. Modulating the compound's physical properties led to a 10-fold improvement in translation resulting in better overall antiviral activity.

  DOI：

  10.1021/jm960083n

文献信息

• Carbonylation of functionalized diamine diols to cyclic ureas: application to derivatives of DMP 450
  作者：Ampofo K. Darko、F. Chris Curran、Chloé Copin、Lisa McElwee-White

  DOI：10.1016/j.tet.2011.04.015

  日期：2011.6

  inhibitor DMP 450 has been achieved via W(CO)6/I2-catalyzed carbonylation of diamine intermediates. Carbonylations of related functionalized diamines to derivatives of the DMP 450 core structure were also examined. Selected diamine diol substrates could be converted to the cyclic urea core structure by catalytic carbonylation without protection of the diol functionality.

  HIV蛋白酶抑制剂DMP 450的环状脲核心结构的合成已经通过W（CO）6 / I 2催化的二胺中间体的羰基化而实现。还检查了相关的官能化二胺羰基化为DMP 450核心结构的衍生物。选定的二胺二醇底物可通过催化羰基化转化为环状脲核心结构，而无需保护二醇的功能。
• Preparation and Structure−Activity Relationship of Novel P1/P1‘-Substituted Cyclic Urea-Based Human Immunodeficiency Virus Type-1 Protease Inhibitors
  作者：David A. Nugiel、Kim Jacobs、Tabitha Worley、Mona Patel、Robert F. Kaltenbach、Dayton T. Meyer、Prabhakar K. Jadhav、George V. De Lucca、Thomas E. Smyser、Ronald M. Klabe、Lee T. Bacheler、Marlene M. Rayner、Steven P. Seitz

  DOI：10.1021/jm960083n

  日期：1996.1.1

  A series of novel P1/P1'-substituted cyclic urea-based HIV-1 protease inhibitors was prepared. Three different synthetic schemes were used to assemble these compounds. The first approach uses amino acid-based starting materials and was originally used to prepare DMP 323. The other two approaches use L-tartaric acid or L-mannitol as the starting material. The required four contiguous R,S,S,R centers of the cyclic urea scaffold are introduced using substrate control methodology. Each approach has specific advantages based on the desired P1/P1' substituent. Designing analogs based on the enzyme's natural substrates provided compounds with reduced activity. Attempts at exploiting hydrogen bond sites in the S1/S1' pocket, suggested by molecular modeling studies, were not fruitful. Several analogs had better binding affinity compared to our initial leads. Modulating the compound's physical properties led to a 10-fold improvement in translation resulting in better overall antiviral activity.