(3aR,6S,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyldihydrofuro[3,4-d][1,3]dioxol-4(3aH)-one | 1320269-76-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3aR,6S,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyldihydrofuro[3,4-d][1,3]dioxol-4(3aH)-one
• CAS: 1320269-76-8
• 化学式: C₂₄H₃₀O₅Si
• 分子量: 426.585
• InChiKey: DPXUCVYKYWELST-PWRODBHTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.01
• 重原子数：
  30.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  53.99
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (3aR,6S,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyldihydrofuro[3,4-d][1,3]dioxol-4(3aH)-one 在 4-二甲氨基吡啶 、 selenium 、 sodium tetrahydroborate 、 N,O-双三甲硅基乙酰胺 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 34.75h， 生成 7-[6-(tert-butyl-diphenyl-silanyloxymethyl)-2,2-dimethyl-tetrahydro-1,3-dioxa-5-selena-pentalen-4-yl]-6-chloro-7H-purine
  参考文献：
  名称：

  新的RNA嘌呤构建基块，4'-硒嘌呤核苷：糖折叠的首次合成和不寻常的混合物

  摘要：

  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。

  DOI：

  10.1002/chem.201300741
• 作为产物：
  描述：

  D-核糖 在 咪唑 、 溴 、 potassium carbonate 、 甲基磺酰氯 作用下， 以 吡啶 、 二氯甲烷 、 水 为溶剂， 反应 28.0h， 生成 (3aR,6S,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyldihydrofuro[3,4-d][1,3]dioxol-4(3aH)-one
  参考文献：
  名称：

  发现新模板，7-取代的 7-Deaza-4'-硫腺苷衍生物作为多激酶抑制剂

  摘要：

  由于潜在的耐药性，抗癌药物的开发仍然具有挑战性。同时抑制与癌症有关的多个靶点可以克服耐药性，并且这些药物比单靶点抑制剂表现出更高的效力。蛋白激酶代表了开发抗癌剂的有希望的目标。由于大多数多激酶抑制剂是杂环，仅占据 ATP 结合位点的铰链和疏水区，我们的目标是设计多激酶抑制剂，基于 ATP 激酶相互作用，将占据核糖袋以及铰链和疏水区. 在此，我们报告发现了一种新的 4'-硫代核苷模板，它是一种具有有效抗癌活性的多激酶抑制剂。体外评估显示铅1g(7-乙炔-7-deaza-4'-thioadenosine) 具有有效的抗癌活性，并在激酶组扫描试验中显着抑制 TRKA、CK1δ 和 DYRK1A / 1B 激酶。我们相信这些发现将为开发抗癌药物铺平道路。

  DOI：

  10.3390/ph14121290

文献信息

• Practical synthesis of 4′-selenopurine nucleosides by combining chlorinated purines and ‘armed’ 4-selenosugar
  作者：Kazuki Ishii、Noriko Saito-Tarashima、Masashi Ota、Seigi Yamamoto、Yasuko Okamoto、Yoshiyuki Tanaka、Noriaki Minakawa

  DOI：10.1016/j.tet.2016.08.071

  日期：2016.10

  The synthesis of a variety of chemically modified oligonucleotides requires the development of a practical synthetic method for its building block, i.e., nucleoside analogs. The one-pot Pummerer-like reaction using hypervalent iodine in combination with 6-chloropurine and an ‘armed’ 4-selenosugar bearing an electron-donating group at the 2-position gave the desired 4′-seleno-6-chloropurine derivative

  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。
• Design and Synthesis of 2,6-Disubstituted-4′-Selenoadenosine-5′-N,N-Dimethyluronamide Derivatives as Human A3 Adenosine Receptor Antagonists
  作者：Hongseok Choi、Kenneth Jacobson、Jinha Yu、Lak Jeong

  DOI：10.3390/ph14040363

  日期：——

  ne derivative 9f exhibited the highest binding affinity at hA3AR. (Ki = 22.7 nM). The 2-H analogues generally showed better binding affinity than the 2-Cl analogues. The cAMP functional assay with 2-Cl-N6-3-iodobenzylamine derivative 9l demonstrated hA3AR antagonist activity. A molecular modelling study suggests an important role of the hydrogen of 5′-uronamide as an essential hydrogen bonding donor

  描述了作为高效和选择性人A 3腺苷受体（hA 3 AR）拮抗剂的一系列新的4'-硒腺苷-5'- N，N-二甲基脲酰胺衍生物。通过向5'-尿嘧啶酰胺位置添加第二个N-甲基，将高度选择性的A 3 AR激动剂4'-硒腺苷-5'- N-甲基尿嘧啶酰胺成功转化为选择性拮抗剂。所有合成的化合物在hA 3 AR处显示中等至高的结合亲和力。在合成的化合物中，2-H- N 6 -3-碘苄基胺衍生物9f在hA 3 AR处显示出最高的结合亲和力。（K i = 22.7 nM）。通常，2-H类似物比2-Cl类似物显示出更好的结合亲和力。用2-Cl- N 6 -3-碘苄基胺衍生物9l进行的cAMP功能测定证明了hA 3 AR拮抗剂的活性。分子模型研究表明5'-乌拉酰胺的氢作为hA 3 AR活化的必要氢键供体的重要作用。
• Structure–activity relationships of 2′-modified-4′-selenoarabinofuranosyl-pyrimidines as anticancer agents
  作者：Jin-Hee Kim、Jinha Yu、Varughese Alexander、Jung Hee Choi、Jayoung Song、Hyuk Woo Lee、Hea Ok Kim、Jungwon Choi、Sang Kook Lee、Lak Shin Jeong

  DOI：10.1016/j.ejmech.2014.06.031

  日期：2014.8

  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.
• Synthesis of 4′-Ethynyl-2′-deoxy-4′-thioribonucleosides and Discovery of a Highly Potent and Less Toxic NRTI
  作者：Kazuhiro Haraguchi、Hisashi Shimada、Keigo Kimura、Genta Akutsu、Hiromichi Tanaka、Hiroshi Abe、Takayuki Hamasaki、Masanori Baba、Elizabeth A. Gullen、Ginger E. Dutschman、Yung-Chi Cheng、Jan Balzarini

  DOI：10.1021/ml2001054

  日期：2011.9.8

  The synthesis of 4'-ethynyl-2'-deoxy-4'-thioribonucleosides was carried out utilizing an electrophilic glycosidation in which 4-ethynyl-4-thiofuranoid glycal 16 served as a glycosyl donor. Electrophilic glycosidation between 16 and the silylated nucleobases (N-4-acetylcytosine, N-6-benzoyladenine, and N-2-acetyl-O-6-diphenylcarbamoylguanine) was carried out in the presence of N-iodosuccinimide (NIS), leading to the exclusive formation of the desired beta-anomers 29, 33, and 36. Anti-HIV studies demonstrated that these 4'-thio nucleosides were less cytotoxic to T-lymphocyte (i.e., MT-4 cells) than the corresponding 4'-ethynyl derivatives of 2'-deoxycytidine (44), 2'-deoxyadenosine (45), and 2'-deoxyguanosine (46). Comparison of the selectivity indices (SI) was made between 4'-thionucleosides (32, 41, and 43) and the corresponding 4'-oxygen analogues 44-46 by using the reported CC50 and EC50 values. In the case of cytosine and adenine nucleosides, comparable SI values were obtained as follows: 32 (545) and 44 (458); 41 (>230) and 45 (1630). In contrast, 4'-ethynyl-2'-deoxy-4'-thioguanosine 43 was found to possess a SI value of >18200, which is 20 times better than that of 46 (933).