dibenzyl ((2R,3S,4S,5R)-1,6-diphenyl-3,4-bis((2-(trimethylsilyl)ethoxy)methoxy)hexane-2,5-diyl)dicarbamate | 153181-18-1

• 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)-1,6-diphenyl-3,4-bis((2-(trimethylsilyl)ethoxy)methoxy)hexane-2,5-diyl)dicarbamate
• 英文别名: benzyl N-[(2R,3S,4S,5R)-1,6-diphenyl-5-(phenylmethoxycarbonylamino)-3,4-bis(2-trimethylsilylethoxymethoxy)hexan-2-yl]carbamate
• CAS: 153181-18-1
• 化学式: C₄₆H₆₄N₂O₈Si₂
• 分子量: 829.194
• InChiKey: MMZADLMRKVMHIP-QHQGJXSCSA-N

物化性质

• 沸点：
  837.6±65.0 °C(Predicted)
• 密度：
  1.094±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  9.46
• 重原子数：
  58
• 可旋转键数：
  27
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  dibenzyl ((2R,3S,4S,5R)-1,6-diphenyl-3,4-bis((2-(trimethylsilyl)ethoxy)methoxy)hexane-2,5-diyl)dicarbamate 在 六羰基钨 、 20 % Pd(OH)2/C 、 碘 、 potassium carbonate 、 环己烯 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 24.0h， 生成 (4R,5S,6S,7R)-hexahydro-5,6-bis[2-(trimethylsilyl)ethoxymethoxy]-4,7-bis(phenylmethyl)-2H-1,3-diazepin-2-one
  参考文献：
  名称：

  官能化二胺二醇羰基化为环状脲：在DMP 450衍生物中的应用

  摘要：

  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。

  DOI：

  10.1016/j.tet.2011.04.015
• 作为产物：
  描述：

  (S)-(S)-2-(((benzyloxy)carbonyl)amino)-3-phenylpropanoic (isobutyl carbonic) anhydride 在 lithium aluminium tetrahydride 、 [VCl3(thf)3] 、 铜 、 N,N-二异丙基乙胺 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 dibenzyl ((2R,3S,4S,5R)-1,6-diphenyl-3,4-bis((2-(trimethylsilyl)ethoxy)methoxy)hexane-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

• Nonpeptide Cyclic Cyanoguanidines as HIV-1 Protease Inhibitors:  Synthesis, Structure−Activity Relationships, and X-ray Crystal Structure Studies
  作者：Prabhakar K. Jadhav、Francis J. Woerner、Patrick Y. S. Lam、C. Nicholas Hodge、Charles J. Eyermann、Hon-Wah Man、Wayne F. Daneker、Lee T. Bacheler、Marlene M. Rayner、James L. Meek、Susan Erickson-Viitanen、David A. Jackson、Joseph C. Calabrese、Margaret Schadt、Chong-Hwan Chang

  DOI：10.1021/jm970524i

  日期：1998.4.1

  native HIV-1 protease and its complexes with the inhibitors suggested that the enzyme flaps are flexible. The movement at the tip of the flaps could be as large as 7 A. On the basis of this observation, cyclic cyanoguanidines have been designed, synthesized, and evaluated as HIV-1 protease (PR) inhibitors. Cyclic cyanoguanidines were found to be very potent inhibitors of HIV-1 protease. The choice of

  天然HIV-1蛋白酶及其抑制剂与复合物的高分辨率X射线结构比较表明，酶瓣具有柔性。襟翼末端的运动可能高达7A。基于此观察结果，已设计，合成并评估了环状氰基胍作为HIV-1蛋白酶（PR）抑制剂。发现环状氰基胍是HIV-1蛋白酶的非常有效的抑制剂。与环状胍相比，环状氰基胍的选择是基于前者的碱性降低。具有环状氰基胍的HIV PR复合物的X射线结构研究表明，与环状脲类似，环状氰基胍也取代了独特的结构水分子。将环状氰基胍的结构-活性关系与相应的环状脲类似物的结构-活性关系进行了比较。使用高分辨率的X射线结构信息已合理化了这两个系列化合物的结合常数的差异。
• 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.