(E)-(2R,5S)-7-[(2S,6S,8R,9S)-8-(3-Amino-propyl)-9-methyl-1,7-dioxa-spiro[5.5]undec-2-yl]-3,5-dimethyl-hept-3-en-2-ol | 756834-84-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (E)-(2R,5S)-7-[(2S,6S,8R,9S)-8-(3-Amino-propyl)-9-methyl-1,7-dioxa-spiro[5.5]undec-2-yl]-3,5-dimethyl-hept-3-en-2-ol
• 英文别名: (E,2R,5S)-7-[(2R,3S,6S,8S)-2-(3-aminopropyl)-3-methyl-1,7-dioxaspiro[5.5]undecan-8-yl]-3,5-dimethylhept-3-en-2-ol
• CAS: 756834-84-1
• 化学式: C₂₂H₄₁NO₃
• 分子量: 367.572
• InChiKey: ZAIIRZVZCNQUNS-VEQSIFFXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  64.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-(2R,5S)-7-[(2S,6S,8R,9S)-8-(3-Amino-propyl)-9-methyl-1,7-dioxa-spiro[5.5]undec-2-yl]-3,5-dimethyl-hept-3-en-2-ol 在 PyOBOP 、 乙胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.58h， 生成 (2S,3R)-4-Amino-3-hydroxy-N-{3-[(2R,3S,6S,8S)-8-((E)-(3S,6R)-6-hydroxy-3,5-dimethyl-hept-4-enyl)-3-methyl-1,7-dioxa-spiro[5.5]undec-2-yl]-propyl}-2-methyl-butyramide
  参考文献：
  名称：

  Synthesis of Bistramide A

  摘要：

  We have developed an efficient and highly stereocontrolled synthesis of bistramide A, a selective activator of protein kinase C isotype delta. Our synthetic strategy featured a novel bidirectional approach for spiroketal construction based on the ring-opening/cross-metathesis sequence employing a highly strained cyclopropenone acetal. The synthesis afforded the final target with the longest linear sequence of 15 steps and provided unambiguous structural determination of bistramide A, including assignment of the previously unknown C(37) stereochemistry.

  DOI：

  10.1021/ja046588h
• 作为产物：
  描述：

  2-{3-[(2R,3S,6S,8S)-8-((E)-(3S,6R)-6-Hydroxy-3,5-dimethyl-hept-4-enyl)-3-methyl-1,7-dioxa-spiro[5.5]undec-2-yl]-propyl}-isoindole-1,3-dione 在 甲胺 作用下， 以 氘代甲醇 为溶剂， 反应 3.0h， 生成 (E)-(2R,5S)-7-[(2S,6S,8R,9S)-8-(3-Amino-propyl)-9-methyl-1,7-dioxa-spiro[5.5]undec-2-yl]-3,5-dimethyl-hept-3-en-2-ol
  参考文献：
  名称：

  Synthesis of Bistramide A

  摘要：

  We have developed an efficient and highly stereocontrolled synthesis of bistramide A, a selective activator of protein kinase C isotype delta. Our synthetic strategy featured a novel bidirectional approach for spiroketal construction based on the ring-opening/cross-metathesis sequence employing a highly strained cyclopropenone acetal. The synthesis afforded the final target with the longest linear sequence of 15 steps and provided unambiguous structural determination of bistramide A, including assignment of the previously unknown C(37) stereochemistry.

  DOI：

  10.1021/ja046588h

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。
• Synthesis of Bistramide A
  作者：Alexander V. Statsuk、Dong Liu、Sergey A. Kozmin

  DOI：10.1021/ja046588h

  日期：2004.8.1

  We have developed an efficient and highly stereocontrolled synthesis of bistramide A, a selective activator of protein kinase C isotype delta. Our synthetic strategy featured a novel bidirectional approach for spiroketal construction based on the ring-opening/cross-metathesis sequence employing a highly strained cyclopropenone acetal. The synthesis afforded the final target with the longest linear sequence of 15 steps and provided unambiguous structural determination of bistramide A, including assignment of the previously unknown C(37) stereochemistry.