4-{6-[4-benzyloxy-2-(tert-butyldiphenylsilanyloxy)-butyl]-tetrahydropyran-2-yl}-3-hydroxybutyric acid ethyl ester | 500208-42-4

• 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: 4-{6-[4-benzyloxy-2-(tert-butyldiphenylsilanyloxy)-butyl]-tetrahydropyran-2-yl}-3-hydroxybutyric acid ethyl ester
• 英文别名: ethyl (3R)-4-[(2R,6S)-6-[(2S)-2-[tert-butyl(diphenyl)silyl]oxy-4-phenylmethoxybutyl]oxan-2-yl]-3-hydroxybutanoate
• CAS: 500208-42-4
• 化学式: C₃₈H₅₂O₆Si
• 分子量: 632.913
• InChiKey: VXJIYWSFRAROEZ-WZJLIZBTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.57
• 重原子数：
  45
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-{6-[4-benzyloxy-2-(tert-butyldiphenylsilanyloxy)-butyl]-tetrahydropyran-2-yl}-3-hydroxybutyric acid ethyl ester 在 palladium dihydroxide 2,2,6,6-tetramethyl-piperidine-N-oxyl 、 sodium hypochlorite 、 sodium chlorite 、 氢气 、 4-甲基苯磺酸吡啶 、 N,N-二异丙基乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 phosphate buffer 、 乙醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 20.0~45.0 ℃ 、101.33 kPa 条件下， 反应 12.0h， 生成 C₆₃H₉₈O₁₄Si₂
  参考文献：
  名称：

  A Concise, Selective Synthesis of the Polyketide Spacer Domain of a Potent Bryostatin Analogue

  摘要：

  [GRAPHICS]A concise, asymmetric synthesis of the polyketide spacer domain portion (C1-C13) of a highly potent bryostatin analogue was developed. The route utilizes asymmetric hydrogenation methodology to install the C3, C5, and C11 stereocenters, while a substrate directed syn reduction sets the C9 stereocenter. The spacer domain 1 is obtained in 10 steps with a 25% overall yield and is readily incorporated into the synthesis of 2.

  DOI：

  10.1021/ol0272390
• 作为产物：
  描述：

  4-{6-[4-benzyloxy-2-(tert-butyldiphenylsilanyloxy)-butyl]-tetrahydropyran-2-yl}-3-oxobutyric acid ethyl ester 在 RuCl₂[(R)-BINAP] 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、7.8 MPa 条件下， 反应 96.0h， 以91%的产率得到4-{6-[4-benzyloxy-2-(tert-butyldiphenylsilanyloxy)-butyl]-tetrahydropyran-2-yl}-3-hydroxybutyric acid ethyl ester
  参考文献：
  名称：

  A Concise, Selective Synthesis of the Polyketide Spacer Domain of a Potent Bryostatin Analogue

  摘要：

  [GRAPHICS]A concise, asymmetric synthesis of the polyketide spacer domain portion (C1-C13) of a highly potent bryostatin analogue was developed. The route utilizes asymmetric hydrogenation methodology to install the C3, C5, and C11 stereocenters, while a substrate directed syn reduction sets the C9 stereocenter. The spacer domain 1 is obtained in 10 steps with a 25% overall yield and is readily incorporated into the synthesis of 2.

  DOI：

  10.1021/ol0272390

文献信息

• Total Synthesis and Initial Biological Evaluation of New B-Ring-Modified Bryostatin Analogs
  作者：Paul A. Wender、Joshua C. Horan、Vishal A. Verma

  DOI：10.1021/ol0620904

  日期：2006.11.9

  [Structure: see text] The total synthesis and preliminary biological evaluation of the first bryostatin analogs (bryologs) to incorporate B-ring substitution are reported. Asymmetric syntheses of two new polyketide "spacer" domains are described, one exploiting the pseudosymmetry of the C1-C13 region. These fragments are convergently joined to the "recognition" domain through a remarkably versatile

  [结构：见正文]报告了第一个纳入B环取代的bryostatin类似物（bryologs）的总合成和初步生物学评估。描述了两个新的聚酮化合物“间隔”域的不对称合成，其中一个利用了C1-C13区域的拟对称性。这些片段通过非常通用的宏缩醛化过程会聚到“识别”域。所得的新类似物对蛋白激酶C（PKC）表现出强大的纳摩尔或皮摩尔亲和力，与溴代他汀相似或更好。
• Efficient Synthetic Access to a New Family of Highly Potent Bryostatin Analogues via a Prins-Driven Macrocyclization Strategy
  作者：Paul A. Wender、Brian A. DeChristopher、Adam J. Schrier

  DOI：10.1021/ja8015632

  日期：2008.5.1

  The step-economical synthesis of a new class of bryostatin analogues that contain the complete oxycarbocyclic core ring system of the bryostatin natural products is reported. These agents are convergently assembled via a highly efficient, functional-group-tolerant, and stereoselective Prins-driven macrocyclization. These tetrahydropyranyl B-ring analogues are among our most potent and efficacious analogues to date, exhibiting nanomolar and picomolar activities in protein kinase C affinity assays as well as in cellular antiproliferation assays.
• A Concise, Selective Synthesis of the Polyketide Spacer Domain of a Potent Bryostatin Analogue
  作者：Paul A. Wender、Alexander V. W. Mayweg、Christopher L. VanDeusen

  DOI：10.1021/ol0272390

  日期：2003.2.1

  [GRAPHICS]A concise, asymmetric synthesis of the polyketide spacer domain portion (C1-C13) of a highly potent bryostatin analogue was developed. The route utilizes asymmetric hydrogenation methodology to install the C3, C5, and C11 stereocenters, while a substrate directed syn reduction sets the C9 stereocenter. The spacer domain 1 is obtained in 10 steps with a 25% overall yield and is readily incorporated into the synthesis of 2.