2-(trimethylsilyl)ethyl (3S,6S,9S)-3-((S)-sec-butyl)-1-((S)-1-((R)-2-((tert-butyldimethylsilyl)oxy)-3-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)propanoyl)pyrrolidin-2-yl)-6-isopropyl-5,8,9-trimethyl-1,4,7,10-tetraoxo-2,5,8,11-tetraazatetradecan-14-oate | 1494545-61-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(trimethylsilyl)ethyl (3S,6S,9S)-3-((S)-sec-butyl)-1-((S)-1-((R)-2-((tert-butyldimethylsilyl)oxy)-3-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)propanoyl)pyrrolidin-2-yl)-6-isopropyl-5,8,9-trimethyl-1,4,7,10-tetraoxo-2,5,8,11-tetraazatetradecan-14-oate
• CAS: 1494545-61-7
• 化学式: C₄₃H₈₁N₅O₁₀Si₂
• 分子量: 884.315
• InChiKey: FLVVGQRAHBQRME-SSNQXALVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.16
• 重原子数：
  60.0
• 可旋转键数：
  21.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  173.12
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  2-(trimethylsilyl)ethyl (3S,6S,9S)-3-((S)-sec-butyl)-1-((S)-1-((R)-2-((tert-butyldimethylsilyl)oxy)-3-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)propanoyl)pyrrolidin-2-yl)-6-isopropyl-5,8,9-trimethyl-1,4,7,10-tetraoxo-2,5,8,11-tetraazatetradecan-14-oate 在 盐酸 、 4-二甲氨基吡啶 、 2-甲基-6-硝基苯甲酸酐 、 四丁基氟化铵 、 4-(二甲胺基丙基)吡啶 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 83.0h， 生成 [(2S)-3-[(3R,10S,13S,16S,19S)-16-[(2S)-butan-2-yl]-10,11,14-trimethyl-2,5,9,12,15,18-hexaoxo-13-propan-2-yl-4-oxa-1,8,11,14,17-pentazabicyclo[17.3.0]docosan-3-yl]-2-hydroxypropyl] 4-methylbenzenesulfonate
  参考文献：
  名称：

  Scalable Solution-Phase Synthesis of the Biologically Active Cyclodepsipeptide Destruxin E, a Potent Negative Regulator of Osteoclast Morphology

  摘要：

  The scalable solution-phase synthesis of the cyclodepsipeptide destruxin E (1) has been achieved. Diastereoselective dihydroxylation of the terminal alkene in a 2-alkoxy-4-pentenoic amide, 7, was successfully accomplished utilizing (DHQD)(2)PHAL as the chiral ligand, and it was found that the use of the L-proline moiety in the substrate as a chiral auxiliary was essential for the induction of high diastereoselectivity to afford the key compound 4 on a gram scale. MNBA-mediated macrolactonization of 3 was also performed without formation of the dimerized product even under higher-dilution conditions, and it is noteworthy that the internal hydrogen bonds and s-cis configuration of the amide bond between N-methylalanine and N-methylvaline in the cyclization precursor 3 would assist in the macrolactonization to provide the macrolactone 2 without forming a dimerized product. Finally, epoxide formation in the side chain afforded destruxin E (1) on a gram scale in high purity (>98%).

  DOI：

  10.1021/jo402437z
• 作为产物：
  描述：

  2-(三甲硅基)乙醇 在 4-二甲氨基吡啶 、 N-羟基-7-氮杂苯并三氮唑 、 palladium on activated carbon 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 123.0h， 生成 2-(trimethylsilyl)ethyl (3S,6S,9S)-3-((S)-sec-butyl)-1-((S)-1-((R)-2-((tert-butyldimethylsilyl)oxy)-3-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)propanoyl)pyrrolidin-2-yl)-6-isopropyl-5,8,9-trimethyl-1,4,7,10-tetraoxo-2,5,8,11-tetraazatetradecan-14-oate
  参考文献：
  名称：

  Scalable Solution-Phase Synthesis of the Biologically Active Cyclodepsipeptide Destruxin E, a Potent Negative Regulator of Osteoclast Morphology

  摘要：

  The scalable solution-phase synthesis of the cyclodepsipeptide destruxin E (1) has been achieved. Diastereoselective dihydroxylation of the terminal alkene in a 2-alkoxy-4-pentenoic amide, 7, was successfully accomplished utilizing (DHQD)(2)PHAL as the chiral ligand, and it was found that the use of the L-proline moiety in the substrate as a chiral auxiliary was essential for the induction of high diastereoselectivity to afford the key compound 4 on a gram scale. MNBA-mediated macrolactonization of 3 was also performed without formation of the dimerized product even under higher-dilution conditions, and it is noteworthy that the internal hydrogen bonds and s-cis configuration of the amide bond between N-methylalanine and N-methylvaline in the cyclization precursor 3 would assist in the macrolactonization to provide the macrolactone 2 without forming a dimerized product. Finally, epoxide formation in the side chain afforded destruxin E (1) on a gram scale in high purity (>98%).

  DOI：

  10.1021/jo402437z