9-Deoxo-FK 506 | 133951-08-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯内酰胺
• 英文名称: 9-Deoxo-FK 506
• 英文别名: 9-deoxo-FK506；9-deoxoFK506；(1S,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-1,14-dihydroxy-12-[(E)-1-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-17-prop-2-enyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-3,10,16-trione
• CAS: 133951-08-3
• 化学式: C₄₄H₇₁NO₁₁
• 分子量: 790.048
• InChiKey: FRSCEVMAMNXXSW-WTDYSYIZSA-N

物化性质

• 沸点：
  872.6±65.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  56
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  161
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  9-Deoxo-FK 506 在 还原型辅酶II(NADPH)四钠盐 作用下， 以 aq. phosphate buffer 为溶剂， 反应 3.0h， 生成 9-hydroxyFK506 、 他克莫司
  参考文献：
  名称：

  Characterization of FK506 Biosynthetic Intermediates Involved in Post-PKS Elaboration

  摘要：

  The post-PKS modification steps of FK506 biosynthesis include C9-oxidation. and 31-O-methylation, but the sequence of these reactions and the exact route have remained unclear. This Study details the post-PM modification pathways in FK506 biosynthesis through the identification of all intermediates and in vitro enzymatic reactions of the cytochrome P450 hydroxylase FkbD and the methyltransferase FkbM. These results complete our understanding of post-PKS, Modification steps to FK506 showing the substrate flexibility of two enzymes involved and the existence of two parallel biosynthetic routes to FK506.

  DOI：

  10.1021/np4001224
• 作为产物：
  描述：

  他克莫司 在 吡啶 、 硫化氢 作用下， 以 甲醇 为溶剂， 生成 9-Deoxo-FK 506
  参考文献：
  名称：

  从与雷帕霉素和FK506由反应有效地除去2-哌啶的Ñ -Bu 4 Ñ + CN -

  摘要：

  雷帕霉素（反应1）和FK506（11）配有Ñ -Bu 4 Ñ + CN - /水溶液。THF导致其哌考林酯亚基的有效切除，分别导致化合物3和12的良好收率。发生两个连续的环裂解反应：三羰基官能团的快速氰化物促进的断裂，然后是较慢的氰化物催化的酯裂解。氰化物试剂为结构复杂的底物中的分子内酯交换反应提供了温和的化学选择性系统。

  DOI：

  10.1016/s0040-4039(00)60634-2

文献信息

• Synthesis of derivatives of FK 506 and FR 900520: modifications at the binding domain
  作者：Gerhard Emmer、Sabine Weber-Roth

  DOI：10.1016/s0040-4020(01)90178-4

  日期：1992.7

  The synthesis of 9-deoxo-FK 506 (13a), 9-deoxo-FR 900520 (13b), 9-deoxo-10(R)-deoxy-FR 900520 (14) and its 10(S) isomer 15 is described. Radical deoxygenation/elemination of the 9-di-hydro-9,10-thiocarbonates 5a,5b,6a and 6b gave the 9,10 unsaturated compounds 7a (7b) or 8a (8b) which were further transferred by hydration or hydrogenation. Different E/Z ratios of 7a (7b) were obtainted when nBu3SnH or [(CH3)3Si]3SiH in combination with AIBN or Et3B were used, allowing the selective preparation of both isomers. Two possible reaction mechanisms are discussed.