(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 | 1204745-28-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (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
• 英文别名: (6S,6aS,8R,9R,10aS,10bR)-8,9-dimethoxy-2,2,8,9-tetramethyl-6,6a,10a,10b-tetrahydro-4H-[1,4]dioxino[2,3-h][1,3]benzodioxin-6-ol
• CAS: 1204745-28-7
• 化学式: C₁₆H₂₆O₇
• 分子量: 330.378
• InChiKey: ZSJYXGCTXBNIOJ-LQTRTAQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  75.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  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 甲基磺酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 168.0h， 以74%的产率得到(6R,6aR,8R,9R,10aS,10bR)-6-chloro-8,9-dimethoxy-2,2,8,9-tetramethyl-6,6a,10a,10b-tetrahydro-4H-[1,4]dioxino[2,3-h][1,3]benzodioxine
  参考文献：
  名称：

  由d-葡萄糖交替合成1,1'-Bis-缬氨酸胺

  摘要：

  由d-葡萄糖分12个步骤实现了1,1'-双缬氨酸胺5的替代合成，该合成以烯酮12为关键中间体，总产率为15％，由d-葡萄糖组成，涉及直接的中间体。葡萄糖衍生的二酮的醛醇缩合反应和钯催化的烯丙基偶联反应是关键步骤。

  DOI：

  10.1021/jo100474p
• 作为产物：
  描述：

  (6aR,8R,9R,10aS,10bR)-8,9-dimethoxy-2,2,8,9-tetramethyl-4,6a,10a,10b-tetrahydro-[1,4]dioxino[2,3-h][1,3]benzodioxin-6-one 在 potassium tri-sec-butyl-borohydride 作用下， 以 四氢呋喃 为溶剂， 以99%的产率得到(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
  参考文献：
  名称：

  The Structure and Stereochemistry of Gabosine K: Syntheses of 7-O-Acetylstreptol and 7-O-Acetyl-1-epi-streptol

  摘要：

  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。

  DOI：

  10.1055/s-0029-1218540

文献信息

• 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）。
• 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.
• Synthesis of chiral hydroxylated enones as potential anti-tumor agents
  作者：Tony K.M. Shing、Ho T. Wu、H.F. Kwok、Clara B.S. Lau

  DOI：10.1016/j.bmcl.2012.10.026

  日期：2012.12

  A series of chiral hydroxylated enones were synthesized as COTC ether analogues to investigate the structural features required for optimal and selective anti-tumor activity. The cytotoxicity of the seven COTC ether analogues against WRL-68 normal and HepG2, HL-60 cancer cell lines were measured. C-4 ether analogues with an aliphatic chain substituent were found to be more favorable than their aromatic counterparts. Inversion of the configuration at C-4 in 5e to give 5f only resulted in reduced selectivity towards cancer cells. These results show that 4-O-pentyl-gabosine D (5e) has optimum selectivity and cytotoxicity towards two cancer cell lines. (c) 2012 Elsevier Ltd. All rights reserved.
• An Alternative Synthesis of 1,1′-Bis-valienamine from <scp>d</scp>-Glucose
  作者：Tony K. M. Shing、Hau M. Cheng

  DOI：10.1021/jo100474p

  日期：2010.5.21

  An alternative synthesis of 1,1′-bis-valienamine 5, which was demonstrated to be a potent trehalase inhibitor, has been achieved from d-glucose in 12 steps with 15% overall yield via enone 12 as the key intermediate, involving a direct aldol reaction of a glucose-derived diketone and a palladium-catalyzed allylic coupling reaction as the key steps.

  由d-葡萄糖分12个步骤实现了1,1'-双缬氨酸胺5的替代合成，该合成以烯酮12为关键中间体，总产率为15％，由d-葡萄糖组成，涉及直接的中间体。葡萄糖衍生的二酮的醛醇缩合反应和钯催化的烯丙基偶联反应是关键步骤。
• 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。