3-(2,2-dimethyl-1,1-diphenyl-1-silapropoxy)-1-(phenylmethoxy)propan-2-ol | 475662-23-8

• 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: 3-(2,2-dimethyl-1,1-diphenyl-1-silapropoxy)-1-(phenylmethoxy)propan-2-ol
• 英文别名: 1-benzyloxy-3-(tert-butyldiphenylsilyloxy)propan-2-ol；1-[Tert-butyl(diphenyl)silyl]oxy-3-phenylmethoxypropan-2-ol
• CAS: 475662-23-8
• 化学式: C₂₆H₃₂O₃Si
• 分子量: 420.624
• InChiKey: IOURDQJSHUJJSU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.14
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(2,2-dimethyl-1,1-diphenyl-1-silapropoxy)-1-(phenylmethoxy)propan-2-ol 在 dimethyl sulfide borane 、 4 A molecular sieve 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 50.0h， 生成 5-[(2,2-dimethyl-1,1-diphenyl-1-silapropoxy)methyl]-5-[(phenylmethoxy)methyl]-3,4,5-trihydrofuran-2-one
  参考文献：
  名称：

  Conformationally Constrained Analogues of Diacylglycerol. 20. The Search for an Elusive Binding Site on Protein Kinase C through Relocation of the Carbonyl Pharmacophore Along the sn-1 Side Chain of 1,2-Diacylglycerol Lactones

  摘要：

  Previous studies with 1,2-diacylglycerol (DAG) lactones, which behave as high-affinity ligands for protein kinase C (PK-C), have established the importance of maintaining intact the pharmacophore triad of two carbonyl moieties (sn-1 and sn-2) and the primary alcohol. In addition, docking studies of DAG-lactones into an empty C1b receptor of PK-Cdelta (as it appears in complex with phorbol 13-O-acetate) have revealed that in either of the two possible binding alternatives (sn-1 or sn-2) only one carbonyl group of the DAG-lactone is involved in binding. Therefore, the unknown receptor for the orphaned carbonyl appears to lie outside the boundaries of this binary complex, possibly residing at the membrane or near the membrane-protein interface. A strategy to locate the optimal location of the unengaged carbonyl was conceived by utilizing a small group of DAG-lactones (1-4) with a highly branched chain adjacent to the sn-2 carbonyl such that sn-2 binding is favored. With these compounds, various locations of the sn-1 carbonyl along the side chain were tested for their binding affinity for PK-C. The results indicate that the location of the side chain sn-1 carbonyl in a DAG-lactone must have perfect mimicry to the sn-1 carbonyl of the parent DAG for it to display high binding affinity. A proposed model from this work is that the missing pharmacophore in the ternary complex, which includes the membrane, is close to the membrane-protein interface.

  DOI：

  10.1021/jm030454h
• 作为产物：
  描述：

  苄基缩水甘油醚 在 4-二甲氨基吡啶 、 水 、 碘 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 33.0h， 生成 3-(2,2-dimethyl-1,1-diphenyl-1-silapropoxy)-1-(phenylmethoxy)propan-2-ol
  参考文献：
  名称：

  一种新的合成路线，朝向单-O-保护的反构象限制的嘧啶无环核苷。

  摘要：

  通过将锂化的2,4-二甲氧基-6-甲基嘧啶与1-苄氧基-3-（叔丁基二苯基甲硅烷氧基）丙-2-酮偶联，获得了单-O-保护的反构象约束的嘧啶无环核苷的新颖合成方法，然后依次进行甲硫基甲基化，环化，羟基化和脱烷基化反应。

  DOI：

  10.1248/cpb.50.1028

文献信息

• Conformationally Constrained Analogues of Diacylglycerol. 20. The Search for an Elusive Binding Site on Protein Kinase C through Relocation of the Carbonyl Pharmacophore Along the <i>sn</i>-1 Side Chain of 1,2-Diacylglycerol Lactones
  作者：Hirokazu Tamamura、Dina M. Sigano、Nancy E. Lewin、Peter M. Blumberg、Victor E. Marquez

  DOI：10.1021/jm030454h

  日期：2004.1.1

  Previous studies with 1,2-diacylglycerol (DAG) lactones, which behave as high-affinity ligands for protein kinase C (PK-C), have established the importance of maintaining intact the pharmacophore triad of two carbonyl moieties (sn-1 and sn-2) and the primary alcohol. In addition, docking studies of DAG-lactones into an empty C1b receptor of PK-Cdelta (as it appears in complex with phorbol 13-O-acetate) have revealed that in either of the two possible binding alternatives (sn-1 or sn-2) only one carbonyl group of the DAG-lactone is involved in binding. Therefore, the unknown receptor for the orphaned carbonyl appears to lie outside the boundaries of this binary complex, possibly residing at the membrane or near the membrane-protein interface. A strategy to locate the optimal location of the unengaged carbonyl was conceived by utilizing a small group of DAG-lactones (1-4) with a highly branched chain adjacent to the sn-2 carbonyl such that sn-2 binding is favored. With these compounds, various locations of the sn-1 carbonyl along the side chain were tested for their binding affinity for PK-C. The results indicate that the location of the side chain sn-1 carbonyl in a DAG-lactone must have perfect mimicry to the sn-1 carbonyl of the parent DAG for it to display high binding affinity. A proposed model from this work is that the missing pharmacophore in the ternary complex, which includes the membrane, is close to the membrane-protein interface.
• A New Synthetic Route towards the Mono-O-protected Anti-conformationally Constrained Pyrimidine Acyclic Nucleoside.
  作者：Chi-Tsan Liu、Tsu-Chiang Tu、Ling-Yih Hsu

  DOI：10.1248/cpb.50.1028

  日期：——

  Novel synthetic approach to mono-O-protected anti-conformationally constrained pyrimidine acyclic nucleoside was attained from the coupling of lithiated 2,4-dimethoxy-6-methylpyrimidine with 1-benzyloxy-3-(tert-butyldiphenylsilyloxy)propan-2-one, followed by the sequential reactions of methylthiomethylation, cyclization, hydroxylation, and dealkylation.

  通过将锂化的2,4-二甲氧基-6-甲基嘧啶与1-苄氧基-3-（叔丁基二苯基甲硅烷氧基）丙-2-酮偶联，获得了单-O-保护的反构象约束的嘧啶无环核苷的新颖合成方法，然后依次进行甲硫基甲基化，环化，羟基化和脱烷基化反应。