4-desacetoxy-6,7-dihydro-5-hydroxymethylleurosidine | 1233368-28-9

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: 4-desacetoxy-6,7-dihydro-5-hydroxymethylleurosidine
• CAS: 1233368-28-9
• 化学式: C₄₃H₅₆N₄O₈
• 分子量: 756.94
• InChiKey: DZPKKFLNGFTTFQ-ATEJYSPXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.26
• 重原子数：
  55.0
• 可旋转键数：
  6.0
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  148.03
• 氢给体数：
  4.0
• 氢受体数：
  11.0

反应信息

• 作为产物：
  描述：

  6,7-dihydro-4-desacetoxy-5-formylvindoline 、 catharanthine sulfate 在 盐酸 、 iron(III) chloride hexahydrate 、 sodium tetrahydroborate 、 ferric(III)oxalate hexahydrate 作用下， 以 2,2,2-三氟乙醇 、 水 为溶剂， 反应 2.5h， 以27%的产率得到4-desacetoxy-6,7-dihydro-5-hydroxymethylvinblastine
  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