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-oxo-hexadec-10-enyl ester | 157430-94-9

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: 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-oxo-hexadec-10-enyl ester
• 英文别名: [(E,3R,4R,5R,6R,9S,13R,15R)-5-[tert-butyl(dimethyl)silyl]oxy-9,15-dimethoxy-4,6,10,13-tetramethyl-3-(methylsulfanylmethoxy)-16-oxohexadec-10-enyl] 2,2-dimethylpropanoate
• CAS: 157430-94-9
• 化学式: C₃₅H₆₈O₇SSi
• 分子量: 661.072
• InChiKey: NJJRHWSKXFYVOG-PYJKVBBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.71
• 重原子数：
  44
• 可旋转键数：
  25
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  106
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  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-oxo-hexadec-10-enyl ester 在 吡啶 、 二异丁基氢化铝 、 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 1.92h， 生成 (10E,16E)-(3R,4R,5R,6R,9S,13R,15R)-5-(tert-Butyl-dimethyl-silanyloxy)-9,15-dimethoxy-4,6,10,13-tetramethyl-3-methylsulfanylmethoxy-19-triethylsilanyloxy-nonadeca-10,16-dienal
  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：

  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 在 吡啶 、 甲酸 、 戴斯-马丁氧化剂 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 1.25h， 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-oxo-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

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。
• 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.