2,2-Dimethyl-propionic acid (3R,4R,5R,6R,9S)-5-(tert-butyl-dimethyl-silanyloxy)-10-hydroxy-9-methoxy-4,6-dimethyl-3-triethylsilanyloxy-decyl ester | 179945-04-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子
• 英文名称: 2,2-Dimethyl-propionic acid (3R,4R,5R,6R,9S)-5-(tert-butyl-dimethyl-silanyloxy)-10-hydroxy-9-methoxy-4,6-dimethyl-3-triethylsilanyloxy-decyl ester
• CAS: 179945-04-1
• 化学式: C₃₀H₆₄O₆Si₂
• 分子量: 577.006
• InChiKey: NVFVKUZMMTZZNQ-IURCNINISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.81
• 重原子数：
  38.0
• 可旋转键数：
  18.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  74.22
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2,2-Dimethyl-propionic acid (3R,4R,5R,6R,9S)-5-(tert-butyl-dimethyl-silanyloxy)-10-hydroxy-9-methoxy-4,6-dimethyl-3-triethylsilanyloxy-decyl ester 在 吡啶 、 disodium hydrogenphosphate 、 sodium amalgam 、 copper(l) iodide 、 正丁基锂 、 甲酸 、 乙酸酐 、 二异丁基氢化铝 、 戴斯-马丁氧化剂 、 氟化氢吡啶 、 溶剂黄146 、 二甲基亚砜 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 水 为溶剂， 反应 25.3h， 生成 (2E,4E,14E,20E)-(7R,8R,9R,10R,13S,17R,19R)-9-(tert-Butyl-dimethyl-silanyloxy)-23-hydroxy-13,19-dimethoxy-8,10,14,17-tetramethyl-7-methylsulfanylmethoxy-tricosa-2,4,14,20-tetraenoic acid ethyl 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：

  (3R,4R,5R,6R)-7-Benzyloxy-5-(tert-butyl-dimethyl-silanyloxy)-4,6-dimethyl-heptane-1,3-diol 在 palladium on activated charcoal 吡啶 、 咪唑 、 六甲基磷酰三胺 、 disodium hydrogenphosphate 、 sodium amalgam 、 三丁基膦 、 氢气 、 碳酸氢钠 、 间氯过氧苯甲酸 、 lithium diisopropyl amide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.32h， 生成 2,2-Dimethyl-propionic acid (3R,4R,5R,6R,9S)-5-(tert-butyl-dimethyl-silanyloxy)-10-hydroxy-9-methoxy-4,6-dimethyl-3-triethylsilanyloxy-decyl 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

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