(2S,3R)-4-(benzyloxy)-3-((tert-butyldimethylsilyl)oxy)-2-methylbutanal | 216868-38-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S,3R)-4-(benzyloxy)-3-((tert-butyldimethylsilyl)oxy)-2-methylbutanal
• 英文别名: (2S,3R)-3-[tert-butyl(dimethyl)silyl]oxy-2-methyl-4-phenylmethoxybutanal
• CAS: 216868-38-1
• 化学式: C₁₈H₃₀O₃Si
• 分子量: 322.52
• InChiKey: HTKGQFWRPXGGGP-WBVHZDCISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.43
• 重原子数：
  22.0
• 可旋转键数：
  8.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  35.53
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (2S,3R)-4-(benzyloxy)-3-((tert-butyldimethylsilyl)oxy)-2-methylbutanal 在 盐酸 、 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 水 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 70.5h， 生成 (3S,4R,5R)-5-(hydroxymethyl)-4-methyl-2-oxotetrahydrofuran-3-aminium chloride
  参考文献：
  名称：

  Synthesis of the Death-Cap Mushroom Toxin α-Amanitin

  摘要：

  alpha-Amanitin is an extremely toxic bicyclic octapeptide isolated from the death-cap mushroom, Amanita phalloides. As a potent inhibitor of RNA polymerase II, alpha-amanitin is toxic to eukaryotic cells. Recent interest in alpha-amanitin arises from its promise as a payload for antibody drug conjugates. For over 60 years, A. phalloides has been the only source of alpha-amanitin. Here we report a synthesis of alpha-amanitin, which surmounts the key challenges for installing the 6-hydroxy-tryptathionine sulfoxide bridge, enantioselective synthesis of (2S,3R,4R)-4,5-dihydroxy-isoleucine, and diastereoselective sulfoxidation.

  DOI：

  10.1021/jacs.7b12698
• 作为产物：
  描述：

  (3R,4R)-5-benzyloxy-3-methyl-4-(tert-butyldimethylsiloxy)-1-pentene 在 sodium periodate 、 四氧化锇 、 N-甲基吗啉氧化物 作用下， 以 甲醇 、 水 、 丙酮 为溶剂， 反应 16.5h， 生成 (2S,3R)-4-(benzyloxy)-3-((tert-butyldimethylsilyl)oxy)-2-methylbutanal
  参考文献：
  名称：

  Synthesis of the Death-Cap Mushroom Toxin α-Amanitin

  摘要：

  alpha-Amanitin is an extremely toxic bicyclic octapeptide isolated from the death-cap mushroom, Amanita phalloides. As a potent inhibitor of RNA polymerase II, alpha-amanitin is toxic to eukaryotic cells. Recent interest in alpha-amanitin arises from its promise as a payload for antibody drug conjugates. For over 60 years, A. phalloides has been the only source of alpha-amanitin. Here we report a synthesis of alpha-amanitin, which surmounts the key challenges for installing the 6-hydroxy-tryptathionine sulfoxide bridge, enantioselective synthesis of (2S,3R,4R)-4,5-dihydroxy-isoleucine, and diastereoselective sulfoxidation.

  DOI：

  10.1021/jacs.7b12698

文献信息

• Synthesis of a 35-Member Stereoisomer Library of Bistramide A: Evaluation of Effects on actin State, Cell Cycle and Tumor Cell Growth
  作者：Iwona E. Wrona、Jason T. Lowe、Thomas J. Turbyville、Tanya R. Johnson、Julien Beignet、John A. Beutler、James S. Panek

  DOI：10.1021/jo802269q

  日期：2009.3.6

  Synthesis and preliminary biological evaluation of a 35-member library of bistramide A stereoisomers are reported. All eight stereoisomers of the C1−C13 tetrahydropyran fragment of the molecule were prepared utilizing crotylsilane reagents 9 and 10 in our [4+2]-annulation methodology. In addition, the four isomers of the C14−C18 γ-amino acid unit were accessed via a Lewis acid mediated crotylation

  报道了双酰胺 A 立体异构体的 35 成员文库的合成和初步生物学评估。在我们的 [4+2] 环化方法中，使用巴豆基硅烷试剂9和10制备了该分子的 C1-C13 四氢吡喃片段的所有八种立体异构体。此外，C14-C18 γ-氨基酸单元的四种异构体通过路易斯酸介导的巴豆化反应使用有机硅烷11的两种对映异构体获得. Bistramide A 的螺旋缩酮亚基在 C39 醇处进行了修饰，以提供立体化学多样化的另一个点。通过使用标准肽偶联方案将片段偶联以提供天然产物的 35 种立体异构体。筛选这些立体化学类似物对细胞肌动蛋白的影响和对癌细胞系（UO-31 肾和 SF-295 CNS）的细胞毒性。这些测定的结果鉴定了一种类似物1.21，其相对于天然产物 bistramide A 具有增强的效力。
• An efficient protocol for the stereoselective dihydroxylation of ene-ester systems
  作者：Stephen A. Hermitage、Alison Murphy、Poul Nielsen、Stanley M. Roberts

  DOI：10.1016/s0040-4020(98)00800-x

  日期：1998.10

  Dihydroxylation of ene ester systems was achieved in good yield and diastereoselectivity under classical catalytic OsO4 and NMO conditions using the intrinsic diastereoselectivity in alpha-methyl beta-OTBS systems. This intrinsic diastereoselection can be reversed using 'super' AD-mix to give the opposite diastereomer also in good selectivity. The regioselection of dihydroxylation in diene esters using a modified 'super' AD-mix was poor. This methodology can be applied towards the synthesis of part structures of the marine macrolide Altohyrtin A. (C) 1998 Elsevier Science Ltd. All rights reserved.