methyl (2E)-2-[(2S,3S,6R)-2-[1-[tert-butyl(dimethyl)silyl]oxy-2-methylpropan-2-yl]-3-hydroxy-2-methoxy-6-prop-2-enyloxan-4-ylidene]acetate | 588728-65-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl (2E)-2-[(2S,3S,6R)-2-[1-[tert-butyl(dimethyl)silyl]oxy-2-methylpropan-2-yl]-3-hydroxy-2-methoxy-6-prop-2-enyloxan-4-ylidene]acetate
• CAS: 588728-65-8
• 化学式: C₂₂H₄₀O₆Si
• 分子量: 428.641
• InChiKey: MTRYCYJRVYRCQG-OXDNSSGVSA-N

物化性质

• 沸点：
  467.9±45.0 °C(Predicted)
• 密度：
  1.03±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 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：

  methyl (2E)-2-[(2S,3S,6R)-2-[1-[tert-butyl(dimethyl)silyl]oxy-2-methylpropan-2-yl]-3-hydroxy-2-methoxy-6-prop-2-enyloxan-4-ylidene]acetate 在 potassium dioxotetrahydroxoosmate(VI) 咪唑 、 4-二甲氨基吡啶 、 四氧化锇 、 N-甲基吲哚酮 、 hydroquinindine-2,5-diphenyl-4,6-pyrimidinediyl diether 、 二乙基甲氧基硼烷 、 碳酸氢钠 、 potassium carbonate 、 戴斯-马丁氧化剂 、 对甲苯磺酸 、 达卡巴嗪 、 triethylamine tris(hydrogen fluoride) 、 potassium hexacyanoferrate(III) 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 、 乙腈 、 叔丁醇 为溶剂， 反应 217.92h， 生成
  参考文献：
  名称：

  Identification of a Tunable Site in Bryostatin Analogs:  C20 Bryologs through Late Stage Diversification

  摘要：

  [GRAPHICS]The C20 region of our bryostatin analogs was identified as a nonpharmacophoric site that could be varied to tune analogs for function and physical properties without significantly affecting their binding affinity for PKC. The use of this site in a late-stage diversification strategy has enabled the facile synthesis of a variety of new C20 analogs, all of which retain nanomolar affinity for PKC, in agreement with our pharmacophore hypothesis.

  DOI：

  10.1021/ol0501931
• 作为产物：
  描述：

  tert-butyl-dimethyl-[2-methyl-2-[(2S)-2-prop-2-enyl-3,4-dihydro-2H-pyran-6-yl]propoxy]silane 在 sodium tetrahydroborate 、 N-甲基吲哚酮 、 cerium(III) chloride 、 四丙基高钌酸铵 、 4 A molecular sieve 、 碳酸氢钠 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 27.25h， 生成 methyl (2E)-2-[(2S,3S,6R)-2-[1-[tert-butyl(dimethyl)silyl]oxy-2-methylpropan-2-yl]-3-hydroxy-2-methoxy-6-prop-2-enyloxan-4-ylidene]acetate
  参考文献：
  名称：

  The Practical Synthesis of a Novel and Highly Potent Analogue of Bryostatin

  摘要：

  Macrocycle 1 is a new highly potent analogue of bryostatin 1, a promising anti-cancer agent currently in human clinical trials. In vitro, 1 displays picomolar affinity for PKC and exhibits over 100-fold greater potency than bryostatin 1 when tested against various human cancer cell lines. Macrocycle 1 can be generated in clinically required amounts by chemical synthesis in only 19 steps (LLS) and represents a new clinical lead for the treatment of cancer.

  DOI：

  10.1021/ja027509+

文献信息

• The Practical Synthesis of a Novel and Highly Potent Analogue of Bryostatin
  作者：Paul A. Wender、Jeremy L. Baryza、Chad E. Bennett、F. Christopher Bi、Stacey E. Brenner、Michael O. Clarke、Joshua C. Horan、Cindy Kan、Emmanuel Lacôte、Blaise Lippa、Peter G. Nell、Tim M. Turner

  DOI：10.1021/ja027509+

  日期：2002.11.1

  Macrocycle 1 is a new highly potent analogue of bryostatin 1, a promising anti-cancer agent currently in human clinical trials. In vitro, 1 displays picomolar affinity for PKC and exhibits over 100-fold greater potency than bryostatin 1 when tested against various human cancer cell lines. Macrocycle 1 can be generated in clinically required amounts by chemical synthesis in only 19 steps (LLS) and represents a new clinical lead for the treatment of cancer.
• Identification of a Tunable Site in Bryostatin Analogs:  C20 Bryologs through Late Stage Diversification
  作者：Paul A. Wender、Jeremy L. Baryza

  DOI：10.1021/ol0501931

  日期：2005.3.1

  [GRAPHICS]The C20 region of our bryostatin analogs was identified as a nonpharmacophoric site that could be varied to tune analogs for function and physical properties without significantly affecting their binding affinity for PKC. The use of this site in a late-stage diversification strategy has enabled the facile synthesis of a variety of new C20 analogs, all of which retain nanomolar affinity for PKC, in agreement with our pharmacophore hypothesis.