[(3R,4R,5R,6R)-5-[tert-butyl(dimethyl)silyl]oxy-3-hydroxy-4,6-dimethyl-7-phenylmethoxyheptyl] 2,2-dimethylpropanoate | 179944-94-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [(3R,4R,5R,6R)-5-[tert-butyl(dimethyl)silyl]oxy-3-hydroxy-4,6-dimethyl-7-phenylmethoxyheptyl] 2,2-dimethylpropanoate
• CAS: 179944-94-6
• 化学式: C₂₇H₄₈O₅Si
• 分子量: 480.761
• InChiKey: DRWDNYVOOWJAAB-LUGTWXOSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.21
• 重原子数：
  33
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [(3R,4R,5R,6R)-5-[tert-butyl(dimethyl)silyl]oxy-3-hydroxy-4,6-dimethyl-7-phenylmethoxyheptyl] 2,2-dimethylpropanoate 在 palladium on activated charcoal 吡啶 、 咪唑 、 六甲基磷酰三胺 、 disodium hydrogenphosphate 、 sodium amalgam 、 copper(l) iodide 、 正丁基锂 、 三丁基膦 、 氢气 、 乙酸酐 、 碳酸氢钠 、 戴斯-马丁氧化剂 、 溶剂黄146 、 间氯过氧苯甲酸 、 lithium diisopropyl amide 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 70.62h， 生成 2,2-Dimethyl-propionic acid (E)-(3R,4R,5R,6R,9S,13R,15R)-5-(tert-butyl-dimethyl-silanyloxy)-9,15-dimethoxy-4,6,10,13-tetramethyl-3-methylsulfanylmethoxy-16-trityloxy-hexadec-10-enyl ester
  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：

  (R)-3-benzyloxy-2-methylpropanal 在 吡啶 、 2,6-二甲基吡啶 、 titanium(IV) isopropylate 、 叔丁基过氧化氢 、 4 A molecular sieve 、 三氟甲磺酸二丁硼 、 potassium tert-butylate 、 三甲基铝 、 二异丁基氢化铝 、 (+)-Weinsaeure-diethylester 、 三乙胺 、 红铝 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 10.0h， 生成 [(3R,4R,5R,6R)-5-[tert-butyl(dimethyl)silyl]oxy-3-hydroxy-4,6-dimethyl-7-phenylmethoxyheptyl] 2,2-dimethylpropanoate
  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
• Toward the Second Generation Synthesis of Aplyronine A: Stereocontrolled Assembly of the C1−C19 Segment by Using an Asymmetric Nozaki−Hiyama−Kishi Coupling
  作者：Kenichi Kobayashi、Yusuke Fujii、Ichiro Hayakawa、Hideo Kigoshi

  DOI：10.1021/ol1029657

  日期：2011.3.4

  An efficient synthesis of the C1-C19 segment of aplyronine A is described. Stereoselective construction of the C14-C15 (E)-trisubstituted double bond and the C13 stereocenter was achieved by using an asymmetric Nozaki-Hiyama-Kishi coupling.
• 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.