| 179945-36-9

• 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
• CAS: 179945-36-9
• 化学式: C₈₉H₁₃₈O₁₄SSi₂
• 分子量: 1520.3
• InChiKey: FHXWQPAIQUUUSY-ZEBIRDHSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  21.52
• 重原子数：
  106.0
• 可旋转键数：
  33.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  144.9
• 氢给体数：
  0.0
• 氢受体数：
  15.0

反应信息

• 作为反应物：
  描述：

  在 甲酸 作用下， 以 乙醚 为溶剂， 反应 1.0h， 以95%的产率得到[(3R,4R,5S,6R,9S,10S,11R)-10-[tert-butyl(dimethyl)silyl]oxy-11-[(2S,4E,6R,8R,10E,12S,15R,16R,17R,18R,20E,22E)-16-[tert-butyl(dimethyl)silyl]oxy-6,12-dimethoxy-8,11,15,17-tetramethyl-18-(methylsulfanylmethoxy)-24-oxo-1-oxacyclotetracosa-4,10,20,22-tetraen-2-yl]-6-[(3,4-dimethoxyphenyl)methoxymethoxy]-1-hydroxy-3,5,9-trimethyldodecan-4-yl] acetate
  参考文献：
  名称：

  以镍/铬介导的偶联反应为特征的第二代苹果碱A的全合成†

  摘要：

  使用Ni / Cr介导的偶联反应作为关键步骤，实现了有效的抗肿瘤海洋大环内酯aplyronine A的第二代全合成。基于最长的线性序列，分38步获得的第二代aplyronine A合成途径的总产率为1.4％。与我们的第一代合成的邻苯丙氨酸A路径相比，第二代合成极大地提高了收率和步骤数。特别是，我们在C13立体中心和C14–C15（ENi / Cr介导的不对称偶联反应））-三取代双键。此外，我们为C21–C28和C29–C34之间的不对称Ni / Cr介导的偶联反应建立了有效的反应条件。因此，该偶联反应以各链段的等摩尔比进行。

  DOI：

  10.1039/c6ob02241c
• 作为产物：
  描述：

  乙酸酐 、 (3E,5E,8R,9R,10R,11R,14S,15E,18R,20R,21E,24S)-10-[tert-butyl(dimethyl)silyl]oxy-24-[(2R,3S,4S,7R,8R,9R,10R)-3-[tert-butyl(dimethyl)silyl]oxy-7-[(3,4-dimethoxyphenyl)methoxymethoxy]-9-hydroxy-4,8,10-trimethyl-12-trityloxydodecan-2-yl]-14,20-dimethoxy-9,11,15,18-tetramethyl-8-(methylsulfanylmethoxy)-1-oxacyclotetracosa-3,5,15,21-tetraen-2-one 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 12.5h， 以100%的产率得到
  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

• 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
• Cytotoxicity and actin depolymerizing activity of aplyronine A, a potent antitumor macrolide of marine origin, and the natural and artificial analogs
  作者：Kiyotake Suenaga、Noriyuki Kamei、Youko Okugawa、Masaki Takagi、Atsushi Akao、Hideo Kigoshi、Kiyoyuki Yamada

  DOI：10.1016/s0960-894x(96)00620-8

  日期：1997.2

  The artificial analogs of aplyronine A (1), a potent cytotoxic and antitumor macrolide, were synthesized and the structure-activity (cytotoxicity and actin depolymerizing activity) studies were performed; the side chain portion in 1 was found to play a key role in both biological activities. (C) 1997, Elsevier Science Ltd.