3,3-bis-(tert-butyldimethylsilanyloxymethyl)-pent-4-enoic acid ethyl ester | 172843-33-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 3,3-bis-(tert-butyldimethylsilanyloxymethyl)-pent-4-enoic acid ethyl ester
• 英文别名: ethyl 3,3-bis<(tert-butyldimethylsiloxy)methyl>-4-pentenoate；ethyl 3,3-bis[(tert-butyldimethylsiloxy)methyl]-4-pentenoate；ethyl 3,3-bis[[tert-butyl(dimethyl)silyl]oxymethyl]pent-4-enoate
• CAS: 172843-33-3
• 化学式: C₂₁H₄₄O₄Si₂
• 分子量: 416.749
• InChiKey: HHYMSNPFCLFMED-UHFFFAOYSA-N

物化性质

• 沸点：
  404.8±45.0 °C(Predicted)
• 密度：
  0.909±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.16
• 重原子数：
  27
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,3-bis-(tert-butyldimethylsilanyloxymethyl)-pent-4-enoic acid ethyl ester 在 Grubbs catalyst first generation 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 甲苯 、 苯 为溶剂， 反应 4.0h， 生成 4,4-Bis[[tert-butyl(dimethyl)silyl]oxymethyl]cyclopent-2-en-1-ol
  参考文献：
  名称：

  通过顺序克莱森重排和闭环易位有效合成新型碳环核苷

  摘要：

  描述了非常有效的合成新的4' - α- C-羟甲基支链碳环核苷的途径。约翰逊原酸酯-克莱森重排，闭环复分解（RCM）从简单的无环前体1,3-二羟基丙酮1开始，成功实现了目标核苷的立体控制合成。核苷碱基（腺嘌呤和胞嘧啶）通过Pd（0）催化的烯丙基烷基化以高度区域控制的方式偶联。

  DOI：

  10.1016/s0040-4039(02)01384-9
• 作为产物：
  描述：

  1,3-bis-O-(tert-butyldimethylsilyl)-1,3-dihydroxy-2-propanone 在 二异丁基氢化铝 、 丙酸 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 28.0h， 生成 3,3-bis-(tert-butyldimethylsilanyloxymethyl)-pent-4-enoic acid ethyl ester
  参考文献：
  名称：

  Conformationally Constrained Analogues of Diacylglycerol. 10. Ultrapotent Protein Kinase C Ligands Based on a Racemic 5-Disubstituted Tetrahydro-2-furanone Template

  摘要：

  5,5-Bis(hydroxymethyl)tetrahydro-2-furanone and its isomer 4,4-bis(hydroxymethyl)tetrahydro-2-furanone were investigated as possible templates for the construction of conformationally constrained analogues of the biologically important second messenger, diacylglycerol (DAG). The former lactone contains embedded within its structure an exact glycerol moiety, while in the latter the ring oxygen has been transposed to the other side of the carbonyl group. Al target compounds were synthesized as racemates from 1,3-dihydroxy-2-propanone. The 5,5-bis(hydroxymethyl)tetrahydro-2-furanone proved to be the better template for the construction of DAG surrogates that were demonstrated to have high binding affinities for the biological target, protein kinase C (PK-C). The simplest target compounds derived from this template (3e and 3f) have one of the hydroxyl moieties functionalized either as a myristate or as an oleate ester. The simplest target compound (9e) derived from the ineffective 4,4-bis(hydroxymethyl)tetrahydro-2-furanone template was investigated only with a myristoyl acyl chain. Reducing the long acyl chain to an acetyl moiety and attaching a compensating lipophilic chain to the lactone ring as an alpha-alkylidene moiety produced compounds 10e and 10f(Z-isomers) and 11e and 11f(E-isomers), which were constructed on the more effective 5,5-bis(hydroxymethyl)tetrahydro-2-furanone template. Targets 14c (Z-isomer) and 15c (E-isomer) were derived, in turn, from 4,4-bis(hydroxymethyl)tetrahydro-2-furan. The affinities of these ligands for PK-C were assessed in terms of their ability to displace bound [H-3-20]phorbol 12,13-dibutyrate (PDBU) from the single isozyme PK-C alpha. The biological data support the hypothesis that the increase in binding affinity for PK-C shown by some of these constrained DAG mimetics appears to be entropic in nature. Two of the designed ligands (10e and 10f) showed the highest affinities (34 and 24 nM, respectively) reported so far for a DAG analogue. Assuming that the interaction between these racemic compounds and PK-C is stereospecific, the potency of the active enantiomer is anticipated to double.

  DOI：

  10.1021/jm950276v

文献信息

• Synthesis and Antiviral Evaluation of Novel 4′-Hydroxymethyl Branched Thioapiosyl Nucleosides
  作者：Jin Woo Kim、Joon Hee Hong

  DOI：10.1002/ardp.200500174

  日期：2005.12

  In this study, we synthesized novel 4′‐hydroxymethyl branched thioapiosyl nucleosides. The thioapiosyl sugar moiety was constructed using sequential ozonolysis and reduction. The natural bases (uracil, thymine, cytosine, and adenine) were efficiently coupled using the Vorbrüggen glycosyl condensation procedure (persilyated base and TMSOTf). The antiviral activities of the synthesized compounds were

  在这项研究中，我们合成了新的 4'-羟甲基支链硫硫磷核苷。使用连续的臭氧分解和还原构建硫辛基糖部分。天然碱基（尿嘧啶、胸腺嘧啶、胞嘧啶和腺嘌呤）使用 Vorbrüggen 糖基缩合程序（过甲硅烷基化碱基和 TMSOTf）有效偶联。对合成化合物的抗病毒活性进行了评估，以对抗 HIV-1、HSV-1、HSV-2 和 HCMV。化合物 19 显示出中等的抗 HIV 活性（EC50 = 19.3 μg/mL），而在高达 100 μM 时没有表现出任何细胞毒性。
• Synthesis and Antiviral Evaluation of Novel 4′-Hydroxymethyl Branched Apiosyl Nucleosides
  作者：Jin Woo Kim、Joon Hee Hong

  DOI：10.1080/15257770500379173

  日期：2006.1

  Novel 4'-hydroxymethyl branched apiosyl nucleosides were synthesized in this study. The introduction of a hydroxymethyl group in the 4'-position was accomplished by a [3,3]-sigmatropic rearrangement. Apiosyl sugar moiety was constructed by sequential ozonolysis and reductions. The natural bases (uracil, thymine, cytosine, and adenine) were efficiently coupled by a classical glycosyl condensation procedure

  在这项研究中合成了新型的4'-羟甲基支链的apiosyl核苷。通过[3,3]-σ重排完成在4'-位引入羟甲基。通过顺序的臭氧分解和还原来构建阿糖基糖部分。天然碱（尿嘧啶，胸腺嘧啶，胞嘧啶和腺嘌呤）通过经典的糖基缩合方法（过碱化的碱和TMSOTf）有效地偶联。评估了合成化合物对HIV-1，HSV-1，HSV-2和HCMV的抗病毒活性。化合物18表现出中等的抗HCMV活性（EC50 = 20.1 microg / mL），最高至100 microM都没有细胞毒性。
• Stereoselective Synthesis of Novel 4′‐Branched and Bicyclo[3.1.0]hexane‐Templated Nucleoside
  作者：Joon Hee Hong

  DOI：10.1081/ncn-120030720

  日期：2004.12.31

  The racemic and stereoselective synthesis of a novel nucleoside 4'-branched and bicyclo[3.1.0]hexane templated nucleoside 15 was accomplished using a [3,3]-sigmatropic rearrangement, an intramolecular carbene cycloaddition reaction and a Curtius rearrangement as the key reactions.

  使用[3,3]-σ重排，分子内卡宾环加成反应和Curtius重排作为关键反应，完成了新的核苷4'-支链和双环[3.1.0]己烷模板化核苷15的外消旋和立体选择性合成。
• Conformationally constrained diacylglycerol analogues
  申请人：The United States of America as represented by the Department of Health

  公开号：US05874464A1

  公开（公告）日：1999-02-23

  Conformationally constrained diacylglycerol analogues, pharmaceutical compositions comprising such analogues, and methods of using such analogues as agonists and antagonists of protein kinase C.

  构象限制的二酰基甘油类似物、包含这种类似物的制药组合物，以及使用这种类似物作为蛋白激酶C的激动剂和拮抗剂的方法。
• Novel Synthesis and Anti-HIV Activity of 4′-Branched Exomethylene Carbocyclic Nucleosides Using a Ring-Closing Metathesis of Triene
  作者：Hua Li、Jin Cheol Yoo、Joon Hee Hong

  DOI：10.1080/15257770802458246

  日期：2008.11.13

  The exomethylene of 6 was successfully constructed from the aldehyde 5 using Eschenmoser's reagents. A triene compound 7 was cyclized successfully using Grubbs' II catalyst to give an exomethylene carbocycle nucleus for the target compound. A Mitsunobu reaction was successfully used to condense the natural bases (adenine, thymine, uracil, and cytosine). The synthesized cytosine analogue 20 showed moderate anti-HIV activity (EC50 = 10.67 M).