4-(tert-butyldimethylsilanyloxy)-3-(tert-butyldimethylsilanyloxymethyl)but-2-enoic acid ethyl ester | 205043-35-2

• 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: 4-(tert-butyldimethylsilanyloxy)-3-(tert-butyldimethylsilanyloxymethyl)but-2-enoic acid ethyl ester
• 英文别名: ethyl 4-((t-butyldimethylsilyl)oxy)-3-(((t-butyldimethylsilyl)-oxy)methyl)but-2-enoate；ethyl 4-[tert-butyl(dimethyl)silyl]oxy-3-[[tert-butyl(dimethyl)silyl]oxymethyl]but-2-enoate；ethyl (2E)-4-(1,1,2,2-tetramethyl-1-silapropoxy)-3-[(1,1,2,2-tetramethyl-1-silapropoxy)methyl]but-2-enoate；Ethyl 4-(t-butyldimethylsilyloxy)-3-[(t-butyldimethyl-silyloxy)methyl]-2-butenoate
• CAS: 205043-35-2
• 化学式: C₁₉H₄₀O₄Si₂
• 分子量: 388.695
• InChiKey: BZLAGZRYXXXUEO-UHFFFAOYSA-N

物化性质

• 沸点：
  388.5±42.0 °C(Predicted)
• 密度：
  0.918±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.52
• 重原子数：
  25
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.84
• 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：

  4-(tert-butyldimethylsilanyloxy)-3-(tert-butyldimethylsilanyloxymethyl)but-2-enoic acid ethyl ester 在 Grubbs catalyst first generation 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 丙酸 、 甲苯 、 苯 为溶剂， 反应 6.0h， 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：

  叔丁基二甲基氯硅烷 在 咪唑 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 49.5h， 生成 4-(tert-butyldimethylsilanyloxy)-3-(tert-butyldimethylsilanyloxymethyl)but-2-enoic acid ethyl ester
  参考文献：
  名称：

  Synthesis and Antiviral Activity of Apio Dideoxy Nucleosides with Azido or Amino Substituent

  摘要：

  Novel apio dideoxynucleosides with azido or amino substituent synthesized starting from 1,3-dihydroxyacetone utilizing an acid-catalyzed 1,4-conjugated addition as a key step and evaluated for antiviral activity. Unfortunately, they were found to be neither active against HIV-1, HSV-1,2 and poliovirus nor toxic.

  DOI：

  10.1080/07328319808003481

文献信息

• Acyclic and Cyclopropyl Analogues of Adenosine Bisphosphate Antagonists of the P2Y₁ Receptor:  Structure−Activity Relationships and Receptor Docking
  作者：Hak Sung Kim、Dov Barak、T. Kendall Harden、José L. Boyer、Kenneth A. Jacobson

  DOI：10.1021/jm010082h

  日期：2001.9.1

  to platelet aggregation, and selective antagonists are sought as potential antithrombotic agents. We reported (Kim et al. J. Med. Chem. 2000, 43, 746-755) that acyclic analogues of adenine nucleotides, containing two phosphate groups on a symmetrically branched aliphatic chain, attached at the 9-position of adenine, are moderately potent P2Y1 receptor antagonists. In this study we have varied the chain

  血小板中 P2Y1 受体的激活有助于血小板聚集，因此寻求选择性拮抗剂作为潜在的抗血栓剂。我们报道 (Kim et al. J. Med. Chem. 2000, 43, 746-755) 腺嘌呤核苷酸的无环类似物，在对称支链脂肪链上含有两个磷酸基团，连接在腺嘌呤的 9 位强效 P2Y1 受体拮抗剂。在这项研究中，我们改变了链结构，包括不对称取代、烯属和环丙基。这些拮抗剂在微摩尔范围内抑制由 30 nM 2-MeS-ADP 诱导的火鸡红细胞膜中的磷脂酶 C 的刺激。在被两个磷酸基团取代的一系列对称支化脂肪族基团中，最佳拮抗剂效力发生在 2-甲基丙基基团。2-氯-N(6)-甲基腺嘌呤衍生物，2-[2-(2-chloro-6-methylaminopurin-9-yl)methyl]propane-1,3-bisoxy(diammoniumphosphate) (7)，是一个完整的P2Y1 受体拮抗剂，IC(50)
• The Synthesis of α,α-Disubstituted α-Amino Acids via Ichikawa Rearrangement
  作者：Piotr Szcześniak、Michał Pieczykolan、Sebastian Stecko

  DOI：10.1021/acs.joc.5b02628

  日期：2016.2.5

  An approach to α,α-disubstituted α-amino acids is reported. The key step is allyl cyanate-to-isocyanate rearrangement. As demonstrated, the resultant allyl isocyanates can be directly trapped with various nucleophiles, for instance, alcohols, amines, and organometallic reagents, to provide a broad range of N-functionalized allylamines. The developed method has been successfully applied in the synthesis

  报道了一种α，α-二取代的α-氨基酸的方法。关键步骤是烯丙基丙烯酸酯到异氰酸酯的重排。如证明的那样，可以用各种亲核试剂例如醇，胺和有机金属试剂直接捕获所得的烯丙基异氰酸酯，以提供广泛的N-官能化烯丙基胺。该方法已成功应用于两种生物活性肽的合成：2-氨基金刚烷-2-羧酸衍生的P2X 7诱发的谷氨酸释放抑制剂和4-氨基-四氢吡喃基-4-羧酸衍生的二肽GSK-2793660。目前作为组织蛋白酶C抑制剂的临床试验正在用于治疗囊性纤维化，非囊性纤维化支气管扩张，ANCA相关血管炎和支气管扩张。
• Using conformationally locked nucleosides to calibrate the anomeric effect: implications for glycosyl bond stability
  作者：Hyung Ryong Moon、Maqbool A. Siddiqui、Guangyu Sun、Igor V. Filippov、Nicholas A. Landsman、Yi-Chien Lee、Kristie M. Adams、Joseph J. Barchi、Jeffrey R. Deschamps、Marc C. Nicklaus、James A. Kelley、Victor E. Marquez

  DOI：10.1016/j.tet.2010.06.044

  日期：2010.8

  and gauche effect play significant roles in steering the North⇆South equilibrium of nucleosides in solution. Two isomeric oxa-bicyclo[3.1.0]hexane nucleosides that are conformationally locked in either the North or the South conformation of the pseudorotational cycle were designed to study the consequences of having the AE operational or not, independent of other parameters. The rigidity of the system

  空间和电子参数，如异头效应 (AE) 和gauche效应在控制溶液中核苷的南北平衡方面起着重要作用。 设计了两个异构的氧杂-双环 [3.1.0] 己烷核苷，它们被构象锁定在假旋转循环的北或南构象中，用于研究 AE 运行与否的后果，独立于其他参数。系统的刚性允许所涉及的轨道的方向设置为“固定”关系，或者是 AE 永久“开启”的反周面，或者是 AE 受损的gauche。这两种替代方案的结果经过高级计算，并通过 X 射线晶体学、糖基键的水解稳定性和 p K a值进行实验测量。
• 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。
• Synthesis and Antiviral Activity of Novel Acyclic Nucleosides:  Discovery of a Cyclopropyl Nucleoside with Potent Inhibitory Activity against Herpesviruses
  作者：Takaaki Sekiyama、Satoshi Hatsuya、Yasuhiro Tanaka、Mamoru Uchiyama、Nobukazu Ono、Satoshi Iwayama、Miki Oikawa、Katsuya Suzuki、Masahiko Okunishi、Takashi Tsuji

  DOI：10.1021/jm9705869

  日期：1998.4.1

  A series of acyclic nucleosides with two hydroxymethyl groups mimicking the 3'- and 5'-hydroxyl groups of the 2'-deoxyribose moiety were prepared and evaluated for their antiherpetic activity. Among those, 9-[[cis-1',2'-bis(hydroxymethyl)cycloprop-1'yl]methyl]guanine (3) showed extremely potent antiviral activity against herpes simplex virus type-1 (HSV-1) with good selectivity. Both enantiomers of 3 were synthesized stal ting from chiral epichlorohydrins, and only one of the enantiomers with 1'S,2'R-configuration (3a) exhibited strong antiherpetic activity (IC50 of 0.020 mu g/mL against HSV-1 Tomioka vs 0.81 mu g/mL for acyclovir). Enantiomer 3a was also more inhibitory than acyclovir against varicella-zoster virus (VZV) but ineffective against human immunodeficiency virus (HIV). Compound 3a is phosphorylated by HSV-1 thymidine kinase (TK) very efficiently. The relationship between conformation and antiherpetic activity in this series of compounds is discussed.