methyl (S)-1-{(S)-2-[(S)-2-amino-3-(methyl)butanamido]-3-[3-(triisopropylsilyloxy)phenyl]propanoyl}hexahydropyridazine-3-carboxylate | 1425924-30-6

• 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: methyl (S)-1-{(S)-2-[(S)-2-amino-3-(methyl)butanamido]-3-[3-(triisopropylsilyloxy)phenyl]propanoyl}hexahydropyridazine-3-carboxylate
• 英文别名: methyl (3S)-1-[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-[3-tri(propan-2-yl)silyloxyphenyl]propanoyl]diazinane-3-carboxylate
• CAS: 1425924-30-6
• 化学式: C₂₉H₅₀N₄O₅Si
• 分子量: 562.825
• InChiKey: WIWUMKFGPIAPBG-GSDHBNRESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.92
• 重原子数：
  39
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl (S)-1-{(S)-2-[(S)-2-amino-3-(methyl)butanamido]-3-[3-(triisopropylsilyloxy)phenyl]propanoyl}hexahydropyridazine-3-carboxylate 、 (4R,5R,6R,7R,E)-1,6-dimethyl-8,9-dioxabicyclo[3.3.1]nonan-7-(2-iodovinyl)-4-carboxylic acid 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 乙腈 为溶剂， 反应 29.0h， 以85%的产率得到(S)-methyl 1(S)-[2(S)-2-[(3R,4R,5R,6R)-3-(1,4-dimethyl-2,9-dioxabicyclo[3.3.1]nonane-6-carboxamido)-(E)-2-(iodovinyl)-3-methylbutanamido]-3-[3-[(triisopropylsilyl)oxy]phenyl]propanoyl]-piperazine-3-carboxylate
  参考文献：
  名称：

  Synthesis of Two Subunits of the Macrolide Domain of the Immunosuppressive Agent Sanglifehrin A and Assembly of a Macrolactone Precursor. Application of Masamune anti-Aldol Condensation

  摘要：

  Asymmetric anti-aldol coupling of a norephedrine-derived ester with an a-chiral aldehyde was used to synthesize a carboxylic acid representing the C13-C19 segment of the macrocyclic domain present in the immunosuppressive agent sanglifehrin A. Felkin addition set configuration at the C14-C17 stereotetrad in this unit in which hydroxyl functions at C15 and C17 were masked as an internal ketal. The carboxyl group of this segment was coupled to the N-terminus of the tripeptide portion (C1-N12) of sanglifehrin A macrolactone to assemble the C1-C19 domain. Synthesis of the C20-C25 subunit of sanglifehrin A containing a (23S) alcohol was completed via asymmetric allylation of (E)-3-iodo-2-methylprop-2-enal followed by oxidative cleavage of the terminal vinyl appendage and a Takai olefination with pinacol dichloromethylboronate. Esterification of this alcohol with a C1-C19 carboxylic acid furnished an open C1-C25 macrolactone precursor, but this substance failed to undergo macrocyclization via intramolecular SuzukiMiyaura coupling.

  DOI：

  10.1021/jo5027595
• 作为产物：
  描述：

  (3-((triisopropylsilyl)oxy)phenyl)methanol 在 咪唑 、 palladium 10% on activated carbon 、 O-allyl-N-[(1-naphthyl)methyl]cinchonidinium bromide 、 水 、 氢气 、 碘 、 溶剂黄146 、 苯甲醚 、 N,N-二异丙基乙胺 、 三苯基膦 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， -10.0~20.0 ℃ 、101.33 kPa 条件下， 反应 61.25h， 生成 methyl (S)-1-{(S)-2-[(S)-2-amino-3-(methyl)butanamido]-3-[3-(triisopropylsilyloxy)phenyl]propanoyl}hexahydropyridazine-3-carboxylate
  参考文献：
  名称：

  不对称相转移催化合成Sanglifehrins的三肽结构域

  摘要：

  三肽（小号）-valinyl-（小号） -米-hydroxyphenylalanyl-（3小号）-piperazate共同免疫抑制剂萨菲菌素从构成氨基酸残基在九个步骤和42％的总收率合成。一个关键的结构为（安装小号）绝对构型在米-hydroxyphenylalanine使用在存在不对称相转移催化ñ - （1-萘基）金鸡尼丁溴化物。Cbz-保护的（小号） -缬氨酸首先耦合至氨基（的小号） -米-triisopropylsilyloxyphenylalanine叔-丁基酯，和在酯裂解后得到的二肽与（3S）-哌嗪酸甲酯连接。

  DOI：

  10.1021/jo3027214

文献信息

• Synthesis of Two Subunits of the Macrolide Domain of the Immunosuppressive Agent Sanglifehrin A and Assembly of a Macrolactone Precursor. Application of Masamune <i>anti</i>-Aldol Condensation
  作者：Khomson Suttisintong、James D. White

  DOI：10.1021/jo5027595

  日期：2015.2.20

  Asymmetric anti-aldol coupling of a norephedrine-derived ester with an a-chiral aldehyde was used to synthesize a carboxylic acid representing the C13-C19 segment of the macrocyclic domain present in the immunosuppressive agent sanglifehrin A. Felkin addition set configuration at the C14-C17 stereotetrad in this unit in which hydroxyl functions at C15 and C17 were masked as an internal ketal. The carboxyl group of this segment was coupled to the N-terminus of the tripeptide portion (C1-N12) of sanglifehrin A macrolactone to assemble the C1-C19 domain. Synthesis of the C20-C25 subunit of sanglifehrin A containing a (23S) alcohol was completed via asymmetric allylation of (E)-3-iodo-2-methylprop-2-enal followed by oxidative cleavage of the terminal vinyl appendage and a Takai olefination with pinacol dichloromethylboronate. Esterification of this alcohol with a C1-C19 carboxylic acid furnished an open C1-C25 macrolactone precursor, but this substance failed to undergo macrocyclization via intramolecular SuzukiMiyaura coupling.
• Synthesis of the Tripeptide Domain of Sanglifehrins Using Asymmetric Phase-Transfer Catalysis
  作者：James D. White、Khomson Suttisintong

  DOI：10.1021/jo3027214

  日期：2013.3.15

  synthesized from the constituent amino acid residues in nine steps and 42% overall yield. A key construction was the installation of (S) absolute configuration in m-hydroxyphenylalanine using asymmetric phase-transfer catalysis in the presence of N-(1-naphthyl)cinchonidinium bromide. Cbz-protected (S)-valine was first coupled to the amino group of (S)-m-triisopropylsilyloxyphenylalanine tert-butyl ester,

  三肽（小号）-valinyl-（小号） -米-hydroxyphenylalanyl-（3小号）-piperazate共同免疫抑制剂萨菲菌素从构成氨基酸残基在九个步骤和42％的总收率合成。一个关键的结构为（安装小号）绝对构型在米-hydroxyphenylalanine使用在存在不对称相转移催化ñ - （1-萘基）金鸡尼丁溴化物。Cbz-保护的（小号） -缬氨酸首先耦合至氨基（的小号） -米-triisopropylsilyloxyphenylalanine叔-丁基酯，和在酯裂解后得到的二肽与（3S）-哌嗪酸甲酯连接。