H-Ile-N(Me)Val-N(Me)Ala-bAla-OEtTMS | 1494545-35-5

• 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: H-Ile-N(Me)Val-N(Me)Ala-bAla-OEtTMS
• 英文别名: 2-trimethylsilylethyl 3-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-amino-3-methylpentanoyl]-methylamino]-3-methylbutanoyl]-methylamino]propanoyl]amino]propanoate
• CAS: 1494545-35-5
• 化学式: C₂₄H₄₈N₄O₅Si
• 分子量: 500.754
• InChiKey: SYBYBNCCXHGDPX-QIJZPMMNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.08
• 重原子数：
  34
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  122
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  H-Ile-N(Me)Val-N(Me)Ala-bAla-OEtTMS 在 盐酸 、 N-羟基-7-氮杂苯并三氮唑 、 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 、 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 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 83.0h， 生成 (3S,6S,9S,16R,21aS)-3-((S)-sec-butyl)-16-((S)-2,3-dihydroxypropyl)-6-isopropyl-5,8,9-trimethyldodecahydropyrrolo[1,2-d][1]oxa[4,7,10,13,16]pentaazacyclononadecine-1,4,7,10,14,17(11H,16H)-hexaone
  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：

  在 N-羟基-7-氮杂苯并三氮唑 、 palladium on activated carbon 、 氢气 、 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 、 异丙醇 为溶剂， 反应 76.0h， 生成 H-Ile-N(Me)Val-N(Me)Ala-bAla-OEtTMS
  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

文献信息

• Parallel Synthesis and Biological Evaluation of Destruxin E Analogs Modified with a Side Chain in the α-Hydroxycarboxylic Acid Moiety
  作者：Masahito Yoshida、Kenta Adachi、Hayato Murase、Hiroshi Nakagawa、Takayuki Doi

  DOI：10.1002/ejoc.201801826

  日期：2019.2.21

  Synthesis and biological evaluation of destruxin E analogs possessing various functional groups in the α‐hydroxycarboxylic acid moiety have been achieved. The (S)‐epoxide moiety in the side chain of α‐hydroxycarboxylic acid could be an essential factor for the induction of morphological changes in OCLs at a lower concentration.

  已经实现了在α-羟基羧酸部分具有各种功能基团的destruxin E类似物的合成和生物学评估。α-羟基羧酸侧链中的（S）-环氧部分可能是在较低浓度下诱导OCL形态变化的重要因素。