(3S,4R,5S,6S,9R,10S)-10-((2R,3R)-5-Methoxy-3-methyl-tetrahydro-furan-2-yl)-4,6-dimethyl-3,5-bis-triethylsilanyloxy-undecane-1,9-diol | 188359-36-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3S,4R,5S,6S,9R,10S)-10-((2R,3R)-5-Methoxy-3-methyl-tetrahydro-furan-2-yl)-4,6-dimethyl-3,5-bis-triethylsilanyloxy-undecane-1,9-diol
• CAS: 188359-36-6
• 化学式: C₃₁H₆₆O₆Si₂
• 分子量: 591.032
• InChiKey: TZWYXRQVORUFES-LTGPVLARSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  39.0
• 可旋转键数：
  21.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  77.38
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (3S,4R,5S,6S,9R,10S)-10-((2R,3R)-5-Methoxy-3-methyl-tetrahydro-furan-2-yl)-4,6-dimethyl-3,5-bis-triethylsilanyloxy-undecane-1,9-diol 在 三丁基膦 、 碳酸氢钠 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 (2R,3R)-2-[(1S,2R,5S,6S,7R,8S)-10-Benzenesulfonyl-2-(3,4-dimethoxy-benzyloxymethoxy)-1,5,7-trimethyl-6,8-bis-triethylsilanyloxy-decyl]-5-methoxy-3-methyl-tetrahydro-furan
  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：

  (2S,3R)-2-Benzyloxy-3-((2R,3R)-5-methoxy-3-methyl-tetrahydro-furan-2-yl)-butan-1-ol 在 Rh/Al₂O₃ disodium hydrogenphosphate 、 sodium amalgam 、 正丁基锂 、 草酰氯 、 氨 、 氢气 、 calcium 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 异丙醇 为溶剂， 生成 (3S,4R,5S,6S,9R,10S)-10-((2R,3R)-5-Methoxy-3-methyl-tetrahydro-furan-2-yl)-4,6-dimethyl-3,5-bis-triethylsilanyloxy-undecane-1,9-diol
  参考文献：
  名称：

  海洋来源的有效抗肿瘤物质Aplyronine A的合成研究：C21–C34段的立体合成

  摘要：

  丙烯醛A（1）的C21–C34片段2是一种有效的海洋来源抗肿瘤物质，是由酰亚胺11以25个步骤（总收率17％）对映选择性合成的。

  DOI：

  10.1016/0040-4039(94)88035-2

文献信息

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

  DOI：10.1016/s0040-4020(01)01206-6

  日期：2002.2

  Artificial analogs of aplyronine A (1), a potent antitumor macrolide, were synthesized and structure–activity (cytotoxicity and actin-depolymerizing activity) relationships were investigated; the side-chain in 1 was found to play a key role in both biological activities.

  合成了一种有效的抗肿瘤大环内酯-邻苯丙氨酸A（1）的人工类似物，并研究了其结构活性（细胞毒性和肌动蛋白解聚活性）之间的关系。发现1中的侧链在两种生物活性中都起着关键作用。
• 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.