(3E,5E,8R,9R,10R,11R,14S,15E,18R,20R,21E,24S)-10-[tert-butyl(dimethyl)silyl]oxy-24-[(2S,3S,4S,7R,8S)-7-[(3,4-dimethoxyphenyl)methoxymethoxy]-3-hydroxy-8-[(2R,3R)-5-methoxy-3-methyloxolan-2-yl]-4-methylnonan-2-yl]-14,20-dimethoxy-9,11,15,18-tetramethyl-8-(methylsulfanylmethoxy)-1-oxacyclotetracosa-3,5,15,21-tetraen-2-one | 228859-27-6

• 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,9R,10R,11R,14S,15E,18R,20R,21E,24S)-10-[tert-butyl(dimethyl)silyl]oxy-24-[(2S,3S,4S,7R,8S)-7-[(3,4-dimethoxyphenyl)methoxymethoxy]-3-hydroxy-8-[(2R,3R)-5-methoxy-3-methyloxolan-2-yl]-4-methylnonan-2-yl]-14,20-dimethoxy-9,11,15,18-tetramethyl-8-(methylsulfanylmethoxy)-1-oxacyclotetracosa-3,5,15,21-tetraen-2-one
• CAS: 228859-27-6
• 化学式: C₆₃H₁₀₈O₁₃SSi
• 分子量: 1133.69
• InChiKey: IXEGAABTGQRWTF-PHNSQFBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  13.93
• 重原子数：
  78
• 可旋转键数：
  24
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  164
• 氢给体数：
  1
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  (3E,5E,8R,9R,10R,11R,14S,15E,18R,20R,21E,24S)-10-[tert-butyl(dimethyl)silyl]oxy-24-[(2S,3S,4S,7R,8S)-7-[(3,4-dimethoxyphenyl)methoxymethoxy]-3-hydroxy-8-[(2R,3R)-5-methoxy-3-methyloxolan-2-yl]-4-methylnonan-2-yl]-14,20-dimethoxy-9,11,15,18-tetramethyl-8-(methylsulfanylmethoxy)-1-oxacyclotetracosa-3,5,15,21-tetraen-2-one 在 乙酸酐 、 二甲基亚砜 作用下， 以 溶剂黄146 为溶剂， 以43%的产率得到(3E,5E,8R,9R,10R,11R,14S,15E,18R,20R,21E,24S)-10-[tert-butyl(dimethyl)silyl]oxy-24-[(2R,3S,4S,7R,8S)-7-[(3,4-dimethoxyphenyl)methoxymethoxy]-8-[(2R,3R)-5-methoxy-3-methyloxolan-2-yl]-4-methyl-3-(methylsulfanylmethoxy)nonan-2-yl]-14,20-dimethoxy-9,11,15,18-tetramethyl-8-(methylsulfanylmethoxy)-1-oxacyclotetracosa-3,5,15,21-tetraen-2-one
  参考文献：
  名称：

  aplyronines B和C的绝对立体化学和合成，aplyronine A的同源物，aplyronine A是一种有效的海洋来源抗肿瘤物质

  摘要：

  对映体选择性地实现了对aplyronines B和C，aplyronine A的同类物的合成，建立了它们的立体结构。

  DOI：

  10.1016/0040-4039(95)00921-x
• 作为产物：
  描述：

  在 titanium(IV) isopropylate 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 以65%的产率得到(3E,5E,8R,9R,10R,11R,14S,15E,18R,20R,21E,24S)-10-[tert-butyl(dimethyl)silyl]oxy-24-[(2S,3S,4S,7R,8S)-7-[(3,4-dimethoxyphenyl)methoxymethoxy]-3-hydroxy-8-[(2R,3R)-5-methoxy-3-methyloxolan-2-yl]-4-methylnonan-2-yl]-14,20-dimethoxy-9,11,15,18-tetramethyl-8-(methylsulfanylmethoxy)-1-oxacyclotetracosa-3,5,15,21-tetraen-2-one
  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

文献信息

• Absolute stereochemistry and synthesis of aplyronines B and C, the congeners of aplyronine A, a potent antitumor substance of marine origin
  作者：Kiyotake Suenaga、Takeshi Ishigaki、Akira Sakakura、Hideo Kigoshi、Kiyoyuki Yamada

  DOI：10.1016/0040-4039(95)00921-x

  日期：1995.7

  Synthesis of aplyronines B and C, the congeners of aplyronine A, was achieved enantioselectively, which established their stereostructures.

  对映体选择性地实现了对aplyronines B和C，aplyronine A的同类物的合成，建立了它们的立体结构。
• Total Synthesis of Aplyronine A, a Potent Antitumor Substance of Marine Origin
  作者：Hideo Kigoshi、Makoto Ojika、Takeshi Ishigaki、Kiyotake Suenaga、Tsuyoshi Mutou、Akira Sakakura、Takeshi Ogawa、Kiyoyuki Yamada

  DOI：10.1021/ja00095a072

  日期：1994.8
• Aplyronine A, a Potent Antitumor Substance of Marine Origin, Aplyronines B and C, and Artificial Analogues:  Total Synthesis and Structure−Cytotoxicity Relationships
  作者：Hideo Kigoshi、Kiyotake Suenaga、Tsuyoshi Mutou、Takeshi Ishigaki、Toshiyuki Atsumi、Hiroyuki Ishiwata、Akira Sakakura、Takeshi Ogawa、Makoto Ojika、Kiyoyuki Yamada

  DOI：10.1021/jo9606113

  日期：1996.1.1

  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.