6,7-dihydro-4-desacetoxy-5-formylvindoline | 1233368-16-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: 6,7-dihydro-4-desacetoxy-5-formylvindoline
• CAS: 1233368-16-5
• 化学式: C₂₂H₂₈N₂O₅
• 分子量: 400.475
• InChiKey: HNNABKZAJOHJLJ-ZQONDGBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.11
• 重原子数：
  29.0
• 可旋转键数：
  3.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  79.31
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  6,7-dihydro-4-desacetoxy-5-formylvindoline 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 0.33h， 以59%的产率得到4-desacetoxy-6,7-dihydro-5-hydroxymethylvindoline
  参考文献：
  名称：

  Total Synthesis and Evaluation of a Key Series of C5-Substituted Vinblastine Derivatives

  摘要：

  A remarkably concise seven- to eight-step total synthesis of a systematic series of key vinblastine derivatives is detailed and used to characterize the importance and probe the role of the C5 ethyl substituent (R = H, Me, Pr, CH=CH(2), C CH, CH(2)OH, and CHO vs Et). The analogues, which bear deep-seated structural changes accessible only by total synthesis, were prepared using a powerful intramolecular [4 + 2]/[3 + 2] cycloaddition cascade of 1,3,4-oxadiazoles ideally suited for use in the assemblage of the vindoline-derived lower subunit followed by their incorporation into the vinblastine analogues through the use of a single-step biomimetic coupling with catharanthine. The evaluation of the series revealed that the tubulin binding site surrounding this C5 substituent is exquisitely sensitive to the presence (Et > H, 10-fold), size (Me <= Et > Pr, 10-fold), shape (Et > CH=CH(2) and C CH, >4-fold), and polarity (Et > CHO > CH(2)OH, >10-20-fold) of this substituent and that on selected occasions only a C5 methyl group may provide analogues that approach the activity observed with the naturally occurring C5 ethyl group.

  DOI：

  10.1021/ja1027748
• 作为产物：
  描述：

  在 sodium periodate 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 以87%的产率得到6,7-dihydro-4-desacetoxy-5-formylvindoline
  参考文献：
  名称：

  Total Synthesis and Evaluation of a Key Series of C5-Substituted Vinblastine Derivatives

  摘要：

  A remarkably concise seven- to eight-step total synthesis of a systematic series of key vinblastine derivatives is detailed and used to characterize the importance and probe the role of the C5 ethyl substituent (R = H, Me, Pr, CH=CH(2), C CH, CH(2)OH, and CHO vs Et). The analogues, which bear deep-seated structural changes accessible only by total synthesis, were prepared using a powerful intramolecular [4 + 2]/[3 + 2] cycloaddition cascade of 1,3,4-oxadiazoles ideally suited for use in the assemblage of the vindoline-derived lower subunit followed by their incorporation into the vinblastine analogues through the use of a single-step biomimetic coupling with catharanthine. The evaluation of the series revealed that the tubulin binding site surrounding this C5 substituent is exquisitely sensitive to the presence (Et > H, 10-fold), size (Me <= Et > Pr, 10-fold), shape (Et > CH=CH(2) and C CH, >4-fold), and polarity (Et > CHO > CH(2)OH, >10-20-fold) of this substituent and that on selected occasions only a C5 methyl group may provide analogues that approach the activity observed with the naturally occurring C5 ethyl group.

  DOI：

  10.1021/ja1027748