methyl (2R)-2-[(7S,8S,9S)-8-methyl-7-(2-phenylmethoxyethyl)-6,10-dioxaspiro[4.5]decan-9-yl]propanoate | 827017-70-9

• 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: methyl (2R)-2-[(7S,8S,9S)-8-methyl-7-(2-phenylmethoxyethyl)-6,10-dioxaspiro[4.5]decan-9-yl]propanoate
• CAS: 827017-70-9
• 化学式: C₂₂H₃₂O₅
• 分子量: 376.493
• InChiKey: GVZWFDSZQFNLBD-HNJRGHQBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (2R)-2-[(7S,8S,9S)-8-methyl-7-(2-phenylmethoxyethyl)-6,10-dioxaspiro[4.5]decan-9-yl]propanoate 在 palladium dihydroxide sodium chlorite 、 sodium dihydrogenphosphate 、 1-氯-N,N,2-三甲基丙烯胺 、 氢气 、 sodium hydride 、 碳酸氢钠 、 potassium tri-sec-butyl-borohydride 、 戴斯-马丁氧化剂 、 氟化氢吡啶 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 生成 盘皮海绵内酯
  参考文献：
  名称：

  Total Synthesis of (+)-Discodermolide:  An Improved Endgame Exploiting a Still−Gennari-Type Olefination with a C1−C8 β-Ketophosphonate Fragment

  摘要：

  An improved, third-generation, total synthesis of (+)-discodermolide, a potent microtubule-stabilizing anticancer agent of marine sponge origin, is achieved in 11.1% yield over 21 steps. Key steps include a Still-Gennari HWE olefination, performed using NaH as the base, between C1-C8 beta-ketophosphonate 7 and C9-C24 aldehyde 8, introducing the (8Z)-alkene with 10:1 selectivity, and K-Selectride reduction of the derived enone 16, installing the (7S)-configuration.

  DOI：

  10.1021/ol0478842
• 作为产物：
  描述：

  (S)-2-[(7R,8S,9S)-9-(2-Benzyloxy-ethyl)-8-methyl-6,10-dioxa-spiro[4.5]dec-7-yl]-propan-1-ol 在 sodium chlorite 、 sodium dihydrogenphosphate 、 碳酸氢钠 、 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 生成 methyl (2R)-2-[(7S,8S,9S)-8-methyl-7-(2-phenylmethoxyethyl)-6,10-dioxaspiro[4.5]decan-9-yl]propanoate
  参考文献：
  名称：

  Total Synthesis of (+)-Discodermolide:  An Improved Endgame Exploiting a Still−Gennari-Type Olefination with a C1−C8 β-Ketophosphonate Fragment

  摘要：

  An improved, third-generation, total synthesis of (+)-discodermolide, a potent microtubule-stabilizing anticancer agent of marine sponge origin, is achieved in 11.1% yield over 21 steps. Key steps include a Still-Gennari HWE olefination, performed using NaH as the base, between C1-C8 beta-ketophosphonate 7 and C9-C24 aldehyde 8, introducing the (8Z)-alkene with 10:1 selectivity, and K-Selectride reduction of the derived enone 16, installing the (7S)-configuration.

  DOI：

  10.1021/ol0478842

文献信息

• Development of a Third-Generation Total Synthesis of (+)-Discodermolide:  An Expedient Still−Gennari-Type Fragment Coupling Utilizing an Advanced β-Ketophosphonate
  作者：Ian Paterson、Isabelle Lyothier

  DOI：10.1021/jo050481a

  日期：2005.7.1

  A novel total synthesis of the complex polyketide discodermolide, a promising anticancer agent of marine sponge origin, has been completed in 11.1% overall yield over 21 linear steps. This third-generation approach features an unprecedented Still-Gennari-type HWE olefination reaction between advanced C1-C8 beta-ketophosphonate 61 and C9-C24 aldehyde 7, introducing the (8z)alkene with 10:1 selectivity. The stereotetrad found in the C1-C8 subunit 61 was established via a highly diastereoselective boron-mediated aldol reaction/in situ reduction between ketone (S)-8 and 3-benzyloxypropanal. The (7S)-configuration was installed by the reduction of enone 73 with K-Selectride.