1,4-anhydro-5-O-tert-butyldiphenylsilyl-2,3-O-isopropylidene-4-seleno-D-ribitol | 1006032-30-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,4-anhydro-5-O-tert-butyldiphenylsilyl-2,3-O-isopropylidene-4-seleno-D-ribitol
• 英文别名: [(3aS,4R,6aR)-2,2-dimethyl-3a,4,6,6a-tetrahydroselenopheno[3,4-d][1,3]dioxol-4-yl]methoxy-tert-butyl-diphenylsilane
• CAS: 1006032-30-9
• 化学式: C₂₄H₃₂O₃SeSi
• 分子量: 475.562
• InChiKey: KAPVBVIBXVFHGS-BDTNDASRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.01
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  27.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,4-anhydro-5-O-tert-butyldiphenylsilyl-2,3-O-isopropylidene-4-seleno-D-ribitol 在 三氟甲磺酸三甲基硅酯 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 17.08h， 生成 1-(5-O-tert-butyldiphenylsilyl-2,3-O-isopropylidene-4-seleno-β-D-ribofuranosyl)uracil
  参考文献：
  名称：

  Structure–activity relationships of 2′-modified-4′-selenoarabinofuranosyl-pyrimidines as anticancer agents

  摘要：

  Based on the potent anticancer activity of the D-arabino-configured cytosine nucleoside ara-C, novel 2'-substituted-4'-selenoarabinofuranosyl pyrimidines 3a-3u, comprising azido, fluoro, and hydroxyl substituents at C-2' were designed, synthesized, and evaluated for anticancer activity. The 2'-azido group was stereoselectively introduced by the Mitsunobu reaction using diphenylphosphoryl azide (DPPA), and the 2'-fluoro group was stereoselectively introduced through the double inversions of stereochemistry via the episelenium intermediate, which was formed by the participation of the selenium atom. Among the compounds tested, the 2'-fluoro derivative 3t (X = NH2, Y = H, R = F) was found to be the most potent anticancer agent and showed more potent anticancer activity than the control, ara-C in all tested human cancer cell lines (HCT116, A549, SNU638, T47D, and PC-3) except the leukemia cell lines (K562). The anticancer activity of the 2'-substituted-4'-selenonucleosides is in the following order: 2'-F > 2'-OH > 2'-N3.

  DOI：

  10.1016/j.ejmech.2014.06.031
• 作为产物：
  描述：

  2,3-O-异亚丙基-D-核糖酸 gamma-内酯 在 吡啶 、 咪唑 、 selenium 、 sodium tetrahydroborate 、 水 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 34.0h， 生成 1,4-anhydro-5-O-tert-butyldiphenylsilyl-2,3-O-isopropylidene-4-seleno-D-ribitol
  参考文献：
  名称：

  通过结合氯化嘌呤和“武装”的4-硒代糖实际合成4'-硒代嘌呤核苷

  摘要：

  多种化学修饰的寡核苷酸的合成需要开发一种实用的合成方法作为其基本组成部分，即核苷类似物。使用高价碘与6-氯嘌呤和在2位带有供电子基团的“武装” 4-硒代糖结合使用的一锅Pummerer样反应，可得到所需的4'-硒代-6-氯嘌呤衍生物。与使用“解除武装”的4-硒代糖的2-位带有吸电子基团的先前方法相比，产率更高。另外，使用2，6-二氯嘌呤作为可转化为鸟嘌呤骨架的核碱基能够实现有效的Pummerer样反应，然后在酸性条件下异构化为所需的N9异构体。

  DOI：

  10.1016/j.tet.2016.08.071

文献信息

• Stereoselective Synthesis of Selenium-Containing Glycoconjugates via the Mitsunobu Reaction
  作者：Luigia Serpico、Mauro De Nisco、Flavio Cermola、Michele Manfra、Silvana Pedatella

  DOI：10.3390/molecules26092541

  日期：——

  A simple and efficient route for the synthesis of new glycoconjugates has been developed. The approach acts as a model for a mini-library of compounds with a deoxy-selenosugar core joined to a polyphenolic moiety with well-known antioxidant properties. An unexpected stereocontrol detected in the Mitsunobu key reaction led to the most attractive product showing a natural d-configuration. Thus, we were

  已经开发了合成新糖缀合物的简单有效途径。该方法充当具有连接到具有众所周知的抗氧化剂特性的多酚部分的脱氧硒糖核心的化合物微型文库的模型。在Mitsunobu键反应中检测到意外的立体声控制，导致最吸引人的产品表现出自然的d-构型。因此，我们能够通过更短和更方便的反应序列从市售的d-核糖中获得目标分子。
• <i>N</i>⁶-Substituted 5′-<i>N</i>-Methylcarbamoyl-4′-selenoadenosines as Potent and Selective A₃ Adenosine Receptor Agonists with Unusual Sugar Puckering and Nucleobase Orientation
  作者：Jinha Yu、Long Xuan Zhao、Jongmi Park、Hyuk Woo Lee、Pramod K. Sahu、Minghua Cui、Steven M. Moss、Eva Hammes、Eugene Warnick、Zhan-Guo Gao、Minsoo Noh、Sun Choi、Hee-Chul Ahn、Jungwon Choi、Kenneth A. Jacobson、Lak Shin Jeong

  DOI：10.1021/acs.jmedchem.7b00241

  日期：2017.4.27

  Potent and selective A3 adenosine receptor (AR) agonists were identified by the replacement of 4'-oxo- or 4'-thionucleosides with bioisosteric selenium. Unlike previous agonists, 4'-seleno analogues preferred a glycosidic syn conformation and South sugar puckering, as shown in the X-ray crystal structure of 5'-N-methylcarbamoyl derivative 3p. Among the compounds tested, N6-3-iodobenzyl analogue 3d

  通过用生物等位硒取代4'-氧代-或4'-硫代核苷来鉴定有效和选择性的A3腺苷受体（AR）激动剂。与先前的激动剂不同，如5'-N-甲基氨基甲酰基衍生物3p的X射线晶体结构所示，4'-硒类似物更喜欢糖苷的顺式构象和南糖起皱。在测试的化合物中，发现N6-3-碘苄基类似物3d是最有效的A3AR完全激动剂（Ki = 0.57 nM），对A1AR和A2AAR的选择性分别是≥800倍和1900倍。在N6-环烷基系列中，2-Cl类似物通常比2-H类似物表现出更好的hA3AR亲和力，而在N6-3-卤代苄基系列中2-H> 2-Cl。N7异构体3t和3u的结合力比相应的N9异构体弱得多，但化合物3t缺乏A3AR活化，似乎是弱者。2-Cl-N6-3-碘苄基类似物3p抑制小分子胶质细胞/单核细胞趋化性诱导的迁移，而在≤50μM时不引起细胞死亡。这表明开发4'-硒代核苷A3AR激动剂作为新型抗中风剂的潜力。
• New RNA Purine Building Blocks, 4′-Selenopurine Nucleosides: First Synthesis and Unusual Mixture of Sugar Puckerings
  作者：Jinha Yu、Jin-Hee Kim、Hyuk Woo Lee、Varughese Alexander、Hee-Chul Ahn、Won Jun Choi、Jungwon Choi、Lak Shin Jeong

  DOI：10.1002/chem.201300741

  日期：2013.4.26

  Writer's blocks: The first synthesis of RNA purine building blocks, 4′‐selenoadenosine and 4′‐selenoguanosine was achieved from D‐ribose by regioisomeric rearrangement, which was confirmed by X‐ray crystallography. 4′‐Selenoadenosine exists in an unusual mixture of north and south conformers in the solid state.

  作者的区块：通过区域异构体重排由D-核糖实现了RNA嘌呤结构单元4'-硒腺苷和4'-硒鸟苷的首次合成，这一点已通过X射线晶体学证实。4'-硒腺苷以固态的北部和南部构象异构体的混合物存在。
• Stereoselective Synthesis of 4′-Selenonucleosides via Seleno-Michael Reaction as Potent Antiviral Agents
  作者：Pramod K. Sahu、Gyudong Kim、Jinha Yu、Ji Yoon Ahn、Jayoung Song、Yoojin Choi、Xing Jin、Jin-Hee Kim、Sang Kook Lee、Sunghyouk Park、Lak Shin Jeong

  DOI：10.1021/ol502899b

  日期：2014.11.7

  Based on the hypothesis that the bulky selenium atom, with 4p orbitals, can sterically hinder the approach of a cellular kinase to 5'-OH for phosphorylation, 4'-selenonucleosides with one-carbon homologation were designed and synthesized via a novel seleno-Michael reaction, with the stereoselectivity controlled by steric effects. 5'-Homo-4'-selenonucleosides (n = 2) demonstrated potent antiherpes simplex virus (HSV-1) activity, indicating that the bulky selenium atom might play a key role in preventing phosphorylation by cellular kinases, resulting in no antiviral activity.
• Stereoselective Synthesis and Conformational Study of Novel 2′,3′-Didehydro-2′,3′-dideoxy-4′-selenonucleosides
  作者：Dilip K. Tosh、Won Jun Choi、Hea Ok Kim、Yoonji Lee、Shantanu Pal、Xiyan Hou、Jungwon Choi、Sun Choi、Lak Shin Jeong

  DOI：10.1021/jo8003277

  日期：2008.6.1

  Stereoselective synthesis of novel 2',3'-didehydro-2',3'dideoxy-4'-selenonnucleosides (4'-seleno-d4Ns) 4a-c was accomplished via 4'-selenoribofuranosyl pyrimidines 11a-c, as key intermediates. 4'-Selenoribofuranosyl pyrimidines 11a-c were efficiently synthesized from D-ribose or D-gulonic gamma-lactone using a Pummerer-type condensation as a key step. Introduction of 2',3'-double bond was achieved by treating cyclic 2',3'-thiocarbonate with 1,3-dimethyl-2-phenyl-1,3,2-diazaphospholidine.