(2S,3S,E)-3-(tert-butyldimethylsilyloxy)-5-iodo-2,4-dimethylpent-4-en-1-ol | 1180131-39-8

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: (2S,3S,E)-3-(tert-butyldimethylsilyloxy)-5-iodo-2,4-dimethylpent-4-en-1-ol
• 英文别名: (E,2S,3S)-3-[tert-butyl(dimethyl)silyl]oxy-5-iodo-2,4-dimethylpent-4-en-1-ol
• CAS: 1180131-39-8
• 化学式: C₁₃H₂₇IO₂Si
• 分子量: 370.346
• InChiKey: PRJKQDRGMDJKFI-ALQBXHKQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.34
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2S,3S,E)-3-(tert-butyldimethylsilyloxy)-5-iodo-2,4-dimethylpent-4-en-1-ol 在 双(三甲基硅烷基)氨基钾 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 15.75h， 生成 tert-butyl-((1E,3S,4S,5Z)-1-iodo-2,4-dimethylnona-1,5-dien-7-yn-3-yloxy)dimethylsilane
  参考文献：
  名称：

  不同的全合成抗有丝分裂剂Leodermatolide。

  摘要：

  微妙但与众不同：生物学上很有前途的抗有丝分裂剂leiodermatolide的立体结构尚不确定。以开环炔烃复分解为关键步骤的短而有效且灵活的全合成方法现已解决了这个难题。所示结构和可能的异构体在1 H NMR光谱中的细微差异证明对于该赋值是无价的。

  DOI：

  10.1002/anie.201206670
• 作为产物：
  描述：

  (2R,3S,E)-((1R,2S)-2-(N-benzyl-2,4,6-trimethylphenylsulfonamido)-1-phenylpropyl) 3-hydroxy-5-iodo-2,4-dimethylpent-4-enoate 在 2,6-二甲基吡啶 、 二异丁基氢化铝 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 4.0h， 生成 (2S,3S,E)-3-(tert-butyldimethylsilyloxy)-5-iodo-2,4-dimethylpent-4-en-1-ol
  参考文献：
  名称：

  不同的全合成抗有丝分裂剂Leodermatolide。

  摘要：

  微妙但与众不同：生物学上很有前途的抗有丝分裂剂leiodermatolide的立体结构尚不确定。以开环炔烃复分解为关键步骤的短而有效且灵活的全合成方法现已解决了这个难题。所示结构和可能的异构体在1 H NMR光谱中的细微差异证明对于该赋值是无价的。

  DOI：

  10.1002/anie.201206670

文献信息

• Selective Deprotection of Silyl Ethers with Sodium Periodate
  作者：Dirk Menche、Jun Li

  DOI：10.1055/s-0028-1088062

  日期：2009.6

  Highly selective deprotection of silyl ethers by NaIO4 in THF-H2O (4:1) is reported. The mild neutral conditions enable efficient applications to complex, polyfunctional, and sensitive substrates.

  据报道，NaIO4 在 THF-H2O (4:1) 中对甲硅烷基醚进行高选择性脱保护。温和的中性条件使得能够有效地应用于复杂、多功能和敏感的基材。
• Synthesis, Molecular Editing, and Biological Assessment of the Potent Cytotoxin Leiodermatolide
  作者：Damien Mailhol、Jens Willwacher、Nina Kausch-Busies、Elizabeth E. Rubitski、Zhanna Sobol、Maik Schuler、My-Hanh Lam、Sylvia Musto、Frank Loganzo、Andreas Maderna、Alois Fürstner

  DOI：10.1021/ja508846g

  日期：2014.11.5

  It was by way of total synthesis that the issues concerning the stereostructure of leiodermatolide (1) have recently been solved; with the target now being unambiguously defined, the mission of synthesis changes as to secure a meaningful supply of this exceedingly scarce natural product derived from a deep-sea sponge. To this end, a scalable route of 19 steps (longest linear sequence) has been developed, which features a catalytic asymmetric propargylation of a highly enolizable beta-keto-lactone, a ring closing alkyne metathesis and a modified Stille coupling as the key transformations. Deliberate digression from this robust blueprint brought a first set of analogues into reach, which allowed the lead qualities of 1 to be assessed. The acquired biodata show that 1 is a potent cytotoxin in human tumor cell proliferation assays, distinguished by GI(50) values in the =3 nM range even for cell lines expressing the Pgp efflux transporter. Studies with human U2OS cells revealed that 1 causes mitotic arrest, micronucleus induction, centrosome amplification and tubulin disruption, even though no evidence for direct tubulin binding has been found in cell-free assays; moreover, the compound does not seem to act through kinase inhibition. Indirect evidence points at centrosome declustering as a possible mechanism of action, which provides a potentially rewarding outlook in that centrosome declustering agents hold promise of being inherently selective for malignant over healthy human tissue.