(1S,2R,3S,4R)-1-O-tert-butyldimethylsilyl-5-hydroxymethyl-2,3-[(2R,3R)-2,3-dimethoxybutan-2,3-dioxy]-5-cyclohexene-1,2,3,4-tetraol | 1204745-30-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1S,2R,3S,4R)-1-O-tert-butyldimethylsilyl-5-hydroxymethyl-2,3-[(2R,3R)-2,3-dimethoxybutan-2,3-dioxy]-5-cyclohexene-1,2,3,4-tetraol
• 英文别名: (2R,3R,4aS,5R,8S,8aR)-8-[tert-butyl(dimethyl)silyl]oxy-6-(hydroxymethyl)-2,3-dimethoxy-2,3-dimethyl-4a,5,8,8a-tetrahydro-1,4-benzodioxin-5-ol
• CAS: 1204745-30-1
• 化学式: C₁₉H₃₆O₇Si
• 分子量: 404.576
• InChiKey: YPCKNYZPYPHEAV-HDVFIIHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.18
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  86.6
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1S,2R,3S,4R)-1-O-tert-butyldimethylsilyl-5-hydroxymethyl-2,3-[(2R,3R)-2,3-dimethoxybutan-2,3-dioxy]-5-cyclohexene-1,2,3,4-tetraol 在 水 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 以87%的产率得到(+)-gabosine E
  参考文献：
  名称：

  （+）-糖氨酸A，D和E † ‡的简便合成

  摘要：

  由作为共用中间体的烯酮11合成了具有相同的三羟基环己烯酮骨架的（+）-糖胺类化合物A（12），D（4）和E（5）。关键的结构单元11是通过分子内的醛酮环化制得的d葡萄糖（8）。

  DOI：

  10.1039/b911810a
• 作为产物：
  描述：

  (1S,2S,3S,4R)-2,3-[(2R,3R)-2,3-dimethoxybutan-2,3-dioxy]-5-hydroxymethyl-4,6-di-O-isopropylidene-5-cyclohexene-1,2,3,4-tetraol 在 咪唑 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 25.0h， 生成 (1S,2R,3S,4R)-1-O-tert-butyldimethylsilyl-5-hydroxymethyl-2,3-[(2R,3R)-2,3-dimethoxybutan-2,3-dioxy]-5-cyclohexene-1,2,3,4-tetraol
  参考文献：
  名称：

  Inhibition of Glutathione S-Transferase M1 by New Gabosine Analogues Is Essential for Overcoming Cisplatin Resistance in Lung Cancer Cells

  摘要：

  A new class of human GST inhibitors has been identified via rational design approach; we report their discovery, synthesis, inhibitory activity, and synergetic effect in combination with cisplatin against A549 lung cancer cell line. The results of this effort show that the lead 4-O-decyl-gabosine D (24) has optimum synergetic effect in A549 human lung adenocarcinoma epithelial cell and that this activity involves inhibition of glutathione S-transferase M1, apparently consistent with siRNA-mediated knockdown of GSTM1 gene.

  DOI：

  10.1021/jm201131n

文献信息

• The Structure and Stereochemistry of Gabosine K: Syntheses of 7-O-Acetylstreptol and 7-O-Acetyl-1-epi-streptol
  作者：Tony Shing、Hau Cheng

  DOI：10.1055/s-0029-1218540

  日期：2010.1

  Gabosine K, whose structure was erroneously assigned previously as 7-O-acetyl-4-epi-streptol, has been synthesized for the first time from d-glucose via a key carbocyclization strategy, intramolecular direct aldol reaction of a 2,6-diketone, in 15 steps with 13.5% overall yield. In the same manner, (+)-7-O-acetyl-streptol has been constructed for NMR spectral comparison. The structure, relative and absolute configurations of (-)-gabosine K are now revised and established as (-)-7-O-acetyl-1-epi-streptol, that is, (1R,2S,3S,4R)-tetrahydroxy-5-acetoxymethylcyclohex-5-ene. Since the specific rotation of the natural product is not available, the absolute configuration of natural gabosine K is either (-)-7-O-acetyl-1-epi-streptol or its enantiomer.

  Gabosine K 的结构以前被错误地归类为 7-O-acetyl-4-epi-streptol ，该化合物是通过一种关键的碳环化策略--2,6-二酮的分子内直接醛醇反应--首次从 d-葡萄糖中合成的，共经过 15 个步骤，总收率为 13.5%。以同样的方式，还构建了 (+)-7-O- 乙酰基链烷醇，用于核磁共振光谱比较。(-)-gabosine K 的结构、相对构型和绝对构型现已修订并确定为 (-)-7-O-乙酰基-1-epi-链醇，即 (1R,2S,3S,4R)-四羟基-5-乙酰氧甲基环己-5-烯。由于无法获得天然产物的特定旋转，因此天然棉子碱 K 的绝对构型是 (-)-7-O- 乙酰基-1-epi-链醇或其对映体。
• Inhibition of Glutathione <i>S</i>-Transferase M1 by New Gabosine Analogues Is Essential for Overcoming Cisplatin Resistance in Lung Cancer Cells
  作者：Chie-Hong Wang、Ho T. Wu、Hau M. Cheng、Tien-Jui Yen、I-Hsuan Lu、Hui Chuan Chang、Shu-Chuan Jao、Tony K. M. Shing、Wen-Shan Li

  DOI：10.1021/jm201131n

  日期：2011.12.22

  A new class of human GST inhibitors has been identified via rational design approach; we report their discovery, synthesis, inhibitory activity, and synergetic effect in combination with cisplatin against A549 lung cancer cell line. The results of this effort show that the lead 4-O-decyl-gabosine D (24) has optimum synergetic effect in A549 human lung adenocarcinoma epithelial cell and that this activity involves inhibition of glutathione S-transferase M1, apparently consistent with siRNA-mediated knockdown of GSTM1 gene.
• Facile syntheses of (+)-gabosines A, D, and E
  作者：Tony K. M. Shing、Hau M. Cheng

  DOI：10.1039/b911810a

  日期：——

  and E (5), which share the same trihydroxycyclohexenone skeleton, were synthesized from enone 11 as the common intermediate. The key building block 11 was accessed by an intramolecular aldol cyclization of a diketone derived from D-glucose (8).

  由作为共用中间体的烯酮11合成了具有相同的三羟基环己烯酮骨架的（+）-糖胺类化合物A（12），D（4）和E（5）。关键的结构单元11是通过分子内的醛酮环化制得的d葡萄糖（8）。