[(3aS,4R,6aR)-2,2-dimethyl-5-oxo-3a,4,6,6a-tetrahydroselenopheno[3,4-d][1,3]dioxol-4-yl]methoxy-tert-butyl-diphenylsilane | 1006032-31-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [(3aS,4R,6aR)-2,2-dimethyl-5-oxo-3a,4,6,6a-tetrahydroselenopheno[3,4-d][1,3]dioxol-4-yl]methoxy-tert-butyl-diphenylsilane
• CAS: 1006032-31-0
• 化学式: C₂₄H₃₂O₄SeSi
• 分子量: 491.561
• InChiKey: KTHLGIMCZTVWQE-DBJIZHOSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.89
• 重原子数：
  30
• 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：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [(3aS,4R,6aR)-2,2-dimethyl-5-oxo-3a,4,6,6a-tetrahydroselenopheno[3,4-d][1,3]dioxol-4-yl]methoxy-tert-butyl-diphenylsilane 在 吡啶 、 三氟甲磺酸三甲基硅酯 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 水 、 甲苯 为溶剂， 反应 34.33h， 生成 1-[3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-4-seleno-β-D-ribofuranosyl]thymine
  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 4-二甲氨基吡啶 、 selenium 、 sodium tetrahydroborate 、 水 、 三乙胺 、 间氯过氧苯甲酸 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 41.25h， 生成 [(3aS,4R,6aR)-2,2-dimethyl-5-oxo-3a,4,6,6a-tetrahydroselenopheno[3,4-d][1,3]dioxol-4-yl]methoxy-tert-butyl-diphenylsilane
  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

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。
• 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 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.
• First Synthesis of 4‘-Selenonucleosides Showing Unusual Southern Conformation
  作者：Lak Shin Jeong、Dilip K. Tosh、Hea Ok Kim、Ting Wang、Xiyan Hou、Ho Seop Yun、Youngjoo Kwon、Sang Kook Lee、Jungwon Choi、Long Xuan Zhao

  DOI：10.1021/ol7025558

  日期：2008.1.1

  The first synthesis of 4'-selenonucleosides was achieved using a Pummerer-type condensation as a key step. All stereoelectronic effects shown in 4'-oxonucleosides were overwhelmed by the size of selenium and steric interactions, driving the conformation to the C2'-endol C3'-exo twist (Southern) conformation.
• 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.