[(3E,5E,8R,9S,10R,11R,14S,15E,18R,20R,21E,24S)-24-[(2S,3S,4S,7R,8S,9R,10R)-9-acetyloxy-7-[2-(dimethylamino)propanoyloxy]-3-hydroxy-4,8,10-trimethyl-12-oxododecan-2-yl]-10-hydroxy-14,20-dimethoxy-9,11,15,18-tetramethyl-2-oxo-1-oxacyclotetracosa-3,5,15,21-tetraen-8-yl] 2-(dimethylamino)-3-methoxypropanoate | 179945-41-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: [(3E,5E,8R,9S,10R,11R,14S,15E,18R,20R,21E,24S)-24-[(2S,3S,4S,7R,8S,9R,10R)-9-acetyloxy-7-[2-(dimethylamino)propanoyloxy]-3-hydroxy-4,8,10-trimethyl-12-oxododecan-2-yl]-10-hydroxy-14,20-dimethoxy-9,11,15,18-tetramethyl-2-oxo-1-oxacyclotetracosa-3,5,15,21-tetraen-8-yl] 2-(dimethylamino)-3-methoxypropanoate
• CAS: 179945-41-6
• 化学式: C₅₇H₉₈N₂O₁₄
• 分子量: 1035.41
• InChiKey: XMUIMTKHHCAMFL-YFGQCASDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.9
• 重原子数：
  73
• 可旋转键数：
  25
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  197
• 氢给体数：
  2
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  [(3E,5E,8R,9S,10R,11R,14S,15E,18R,20R,21E,24S)-24-[(2S,3S,4S,7R,8S,9R,10R)-9-acetyloxy-7-[2-(dimethylamino)propanoyloxy]-3-hydroxy-4,8,10-trimethyl-12-oxododecan-2-yl]-10-hydroxy-14,20-dimethoxy-9,11,15,18-tetramethyl-2-oxo-1-oxacyclotetracosa-3,5,15,21-tetraen-8-yl] 2-(dimethylamino)-3-methoxypropanoate 在 lithium tri(t-butoxy)aluminum hydride 作用下， 以 四氢呋喃 为溶剂， 以60%的产率得到[(3E,5E,8R,9S,10R,11R,14S,15E,18R,20R,21E,24S)-24-[(2S,3S,4S,7R,8S,9R,10R)-9-acetyloxy-7-[2-(dimethylamino)propanoyloxy]-3,12-dihydroxy-4,8,10-trimethyldodecan-2-yl]-10-hydroxy-14,20-dimethoxy-9,11,15,18-tetramethyl-2-oxo-1-oxacyclotetracosa-3,5,15,21-tetraen-8-yl] 2-(dimethylamino)-3-methoxypropanoate
  参考文献：
  名称：

  Aplyronine A, a Potent Antitumor Substance of Marine Origin, Aplyronines B and C, and Artificial Analogues:  Total Synthesis and Structure−Cytotoxicity Relationships

  摘要：

  The enantioselective total synthesis of aplyronine A (1), a potent antitumor substance of marine origin, was achieved by a convergent-approach Three segments 4, 5, and 6, corresponding to the C5-C11, C21-C27, and C28-C34 portions of aplyronine A (1), were prepared using:the Evans aldol reaction and the Sharpless epoxidation as key steps. The coupling reaction of 4 with iodide 7 followed by julia olefination with sulfone 8 gave the C5-C20 segment 9, while the julia coupling reaction between segments 5 and 6 provided the C21-C34 segment 10. Julia olefination between segments 9 and 10 and the subsequent four-carbon homologation reaction led to seco acid 83, which was converted into aplyronine A (1) by Yamaguchi lactonization followed by the introduction of two amino acids. The use of the [(3,4-dimethoxybenzyl)oxy]methyl group as a protecting group for the hydroxyl at C29 was crucial for this synthesis. The enantioselective synthesis of two natural congeners, aplyronines B (2) acid C (3), was also carried out using the intermediates for the synthesis of 1, which determined the absolute stereostructures of 2 and 3 unambiguously. To study the structure-cytotoxicity relationships of aplyronines, artificial analogues of 1 were synthesized and their cytotoxicities were evaluated: the trimethylserine moiety, two hydroxyl groups, and the side-chain portion in 1 turned out to be important in the potent cytotoxicity shown by 1. Biological studies with aplyronine A (1) showed that 1 inhibited polymerization of G-actin to F-actin and depolymerized F-actin to G-actin.

  DOI：

  10.1021/jo9606113
• 作为产物：
  描述：

  [(3Z,5Z,8R,9S,10R,11R,14S,15Z,18R,20R,21Z,24S)-24-[(E,2S,3S,4S,7R,8S,9R,10R)-9-乙酰氧基-7-[(2S)-2-二甲基氨基丙酰基]氧基-12-(甲酰基-甲基氨基)-3-羟基-4,8,10-三甲基十二碳-11-烯-2-基]-10-羟基-14,20-二甲氧基-9,11,15,18-四甲基-2-氧代-1-氧杂环二十四碳-3,5,15,21-四烯-8-基](2S)-2-二甲基氨基-3-甲氧基丙烷酸酯 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.17h， 以88%的产率得到[(3E,5E,8R,9S,10R,11R,14S,15E,18R,20R,21E,24S)-24-[(2S,3S,4S,7R,8S,9R,10R)-9-acetyloxy-7-[2-(dimethylamino)propanoyloxy]-3-hydroxy-4,8,10-trimethyl-12-oxododecan-2-yl]-10-hydroxy-14,20-dimethoxy-9,11,15,18-tetramethyl-2-oxo-1-oxacyclotetracosa-3,5,15,21-tetraen-8-yl] 2-(dimethylamino)-3-methoxypropanoate
  参考文献：
  名称：

  Aplyronine A，一种有效的海洋来源抗肿瘤大环内酯类药物，同族的aplyronines B和C：分离，结构和生物活性

  摘要：

  从海兔Aplysia kurodai中分离到了一种有效的抗肿瘤大环内酯-Aplyronine A（2），以及同类的aplyronines B（3）和C（4）。通过仪器分析（主要是NMR和MS）和对苯丙氨酸A（2）的化学降解获得的片段的对映选择性合成，确定了苯丙氨酸A（2）的绝对立体结构。还阐明了鸭绿素B（3）和C（4）的结构。肾上腺素A（2）的细胞毒性和抗肿瘤活性进行了评估。

  DOI：

  10.1016/j.tet.2007.02.011