1-[2-O-(tert-butyldimethylsilyl)-β-D-erythro-pentofuran-3-ulosyl]uracil | 162611-11-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-[2-O-(tert-butyldimethylsilyl)-β-D-erythro-pentofuran-3-ulosyl]uracil
• 英文别名: 1-[(2R,3S,5R)-3-[tert-butyl(dimethyl)silyl]oxy-5-(hydroxymethyl)-4-oxo-tetrahydrofuran-2-yl]pyrimidine-2,4-dione；1-[(2R,3S,5R)-3-[tert-butyl(dimethyl)silyl]oxy-5-(hydroxymethyl)-4-oxooxolan-2-yl]pyrimidine-2,4-dione
• CAS: 162611-11-2
• 化学式: C₁₅H₂₄N₂O₆Si
• 分子量: 356.451
• InChiKey: RYNUWKOCPDBCJI-OASPWFOLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.39
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-[2-O-(tert-butyldimethylsilyl)-β-D-erythro-pentofuran-3-ulosyl]uracil 在 potassium carbonate 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 为溶剂， 生成 1-[2,5-di-O-(tert-butyldimethylsilyl)-3-C-ethynyl-β-D-ribo-pentofuranosyl]uracil
  参考文献：
  名称：

  Rapid and efficient stereocontrolled synthesis of C-3′-ethynyl ribo and xylonucleosides by organocerium additions to 3′-ketonucleosides

  摘要：

  In order to prepare new anti-retroviral nucleoside analogues, the effect of the group at C-5' on the addition of lithium and cerium trimethylsilylacetylide on 3'-ketonucleosidcs (R(1) = H, R(1) = TBDMS) derived from adenosine and uridine was studied. The best results in respect of yield (56 to 81%) and diastereoselectivity (95:5 to >98:2) were obtained with a cerium reagent (RCcCl(2)).

  DOI：

  10.1016/0040-4039(94)02434-d
• 作为产物：
  描述：

  5’-O-（4,4’-二甲氧基三苯甲基）-2’-O-叔丁基二甲基硅基尿苷 在 吡啶 、 chromium(VI) oxide 、 3 A molecular sieve 、 乙酸酐 、 三氯乙酸 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 1.5h， 生成 1-[2-O-(tert-butyldimethylsilyl)-β-D-erythro-pentofuran-3-ulosyl]uracil
  参考文献：
  名称：

  Stereoselective Preparation of 3'-C-Allyluridines and 3'-Spiro-gamma-Lactone Uridine Analogues.

  摘要：

  Grignard reactions of 3'-ketouridines 1a-c with allylmagnesium bromide and CeCl3 afforded novel 3'-C-allyluridines 2a-c and 3d-e. The diprotected 3'-keto nucleosides 1a-c afforded xylo-configurated compounds 2a-c and the 5'-unprotected 3'-keto nucleosides 1d-e afforded mixtures of xylo- and ribo-configurated compounds 2d/3d and 2e/3e. The allyluridine 2a was converted into the diol 4 by standard hydroboration and further oxidised to the 3'-spiro-gamma-lactone nucleoside 5. This compound and its deprotected analogue 6 are the first examples of a novel class of 3'-spiro nucleoside analogues.

  DOI：

  10.3891/acta.chem.scand.50-1030

文献信息

• Nucleosides and Nucleotides. 175. Structural Requirements of the Sugar Moiety for the Antitumor Activities of New Nucleoside Antimetabolites, 1-(3-<i>C</i>-Ethynyl-β-<scp>d</scp>-<i>r</i><i>ibo</i>-pentofuranosyl)cytosine and -uracil
  作者：Hideshi Hattori、Eisuke Nozawa、Tomoharu Iino、Yuichi Yoshimura、Satoshi Shuto、Yuji Shimamoto、Makoto Nomura、Masakazu Fukushima、Motohiro Tanaka、Takuma Sasaki、Akira Matsuda

  DOI：10.1021/jm9801814

  日期：1998.7.1

  1-(3-C-ethynyl-beta-d-ribo-pentofuranosyl)uracil (EUrd) and its cytosine congener (ECyd) as potential multifunctional antitumor nucleoside antimetabolites. They showed potent and broad-spectrum antitumor activity against various human and mouse tumor cells in vitro and in vivo. To clarify the structure-activity relationship of the sugar moiety, various 3'-C-carbon-substituted analogues, such as 1-propynyl

  我们以前设计1-（3-C-乙炔基-β-d-核糖基戊呋喃糖基）尿嘧啶（EUrd）及其胞嘧啶同源物（ECyd）作为潜在的多功能抗肿瘤核苷抗代谢物。他们在体外和体内显示出对各种人类和小鼠肿瘤细胞的有效和广谱抗肿瘤活性。为了阐明糖部分的结构-活性关系，合成了ECyd和EUrd的各种3'-C-碳取代的类似物，例如1-丙炔基，1-丁炔基，乙烯基，乙基和环丙基衍生物。我们还制备了具有不同构型的ECyd和EUrd的3'-脱氧类似物和3'-同源物，以确定3'-羟基的作用以及3'-碳原子与乙炔基之间的长度以及2'- ECyd的乙炔基衍生物可确定乙炔基的空间要求。这些核苷对小鼠白血病L1210和人KB细胞的体外肿瘤细胞生长抑制活性表明ECyd和EUrd是该系列中最有效的抑制剂，对于L1210细胞，IC50值为0.016和0.13 microM，对于L1210细胞，IC50值为0.028和0.029 microM
• Diastereofacial Selective Addition of Ethynylcerium Reagent and Barton−McCombie Reaction as the Key Steps for the Synthesis of <i>C</i>-3‘-Ethynylribonucleosides and of <i>C</i>-3‘-Ethynyl-2‘-deoxyribonucleosides
  作者：Pierre M. J. Jung、Alain Burger、Jean-François Biellmann

  DOI：10.1021/jo9704568

  日期：1997.11.1

  starting from the corresponding nucleosides. The desired stereochemistry of the C-3' tertiary alcohol was obtained by reaction of an ethynylcerium-lithium reagent on a 3'-ketonucleoside with the hydroxyl group at C-5' unprotected. The 2'-deoxygenation was performed by a Barton-McCombie reaction under appropriate conditions where the addition of tin hydride to the triple bond was suppressed. Evaluation of

  我们描述了从相应的核苷开始制备3'-炔基尿苷4a和-腺苷4b以及3'-炔基-2'-脱氧尿苷16a和-腺苷16b的方法。通过使乙炔基铈-锂试剂在3'-酮核苷上与未保护的C-5'处的羟基反应，可获得所需的C-3'叔醇立体化学。通过Barton-McCombie反应在适当的条件下进行2'-脱氧，其中在三键上抑制了氢化锡的添加。报道了对C-3'修饰的核苷的抗HIV活性的评估。
• Synthesis of 3′-β-carbamoylmethylcytidine (CAMC) and its derivatives as potential antitumor agents
  作者：Satoshi Ichikawa、Noriaki Minakawa、Satoshi Shuto、Motohiro Tanaka、Takuma Sasaki、Akira Matsuda

  DOI：10.1039/b517602f

  日期：——

  3′-β-Carbamoylmethylcytidine (CAMC) and its derivatives were synthesized using an intramolecular Reformatsky-type reaction promoted by SmI2 as the key step. In vitro tumor cell growth inhibitory activity was evaluated and CAMC was found to exhibit potent cytotoxicity against various human tumor cell lines. From a structure–activity relationship study it was postulated that the cytotoxic mechanism of action of CAMC did not require phosphorylation at the 5′-hydroxyl group. This study provides a novel strategy for the development of a new type of antitumor nucleoside.

  以 SmI2 促进的分子内 Reformatsky 型反应为关键步骤，合成了 3â²-β-Carbamoylmethylcytidine (CAMC) 及其衍生物。对体外肿瘤细胞生长抑制活性进行了评估，发现 CAMC 对多种人类肿瘤细胞株具有很强的细胞毒性。根据结构与活性关系研究推测，CAMC 的细胞毒性作用机制不需要 5²-羟基上的磷酸化。这项研究为开发新型抗肿瘤核苷提供了一种新策略。
• Nucleosides and Nucleotides. 163. Synthesis of 3‘-β-Branched Uridine Derivatives via Intramolecular Reformatsky-Type Reaction Promoted by Samarium Diiodide¹
  作者：Satoshi Ichikawa、Satoshi Shuto、Noriaki Minakawa、Akira Matsuda

  DOI：10.1021/jo961665f

  日期：1997.3.1

  A novel efficient method for the synthesis of 3'-beta-branched uridines starting from uridine was developed, in which a SmI2-promoted intramolecular Reformatsky-type reaction was effectively used. 5'-O-(Bromoacetyl)-3'-ketouridine derivatives 12, 26, and 27 were synthesized from uridine and were subjected to an intramolecular Reformatsky-type reaction. When 12, 26, and 27 were treated with 2.0 equiv of SmI2 in THF at -78 degrees C, intramolecular carbon-carbon bond formation at the 3'-beta-position proceeded smoothly to give the corresponding 3',5'-lactones 14, 28, and 29 in high yields, respectively. Treatment of 28 with NH3/MeOH gave the 3'-beta-branched uridine derivative 32 quantitatively, which was then deprotected to give 3'-C-(carbamoylmethyl)uridine (33).
• Rapid and efficient stereocontrolled synthesis of C-3′-ethynyl ribo and xylonucleosides by organocerium additions to 3′-ketonucleosides
  作者：Pierre M.J Jung、Alain Burger、Jean-Francois Biellmann

  DOI：10.1016/0040-4039(94)02434-d

  日期：1995.2

  In order to prepare new anti-retroviral nucleoside analogues, the effect of the group at C-5' on the addition of lithium and cerium trimethylsilylacetylide on 3'-ketonucleosidcs (R(1) = H, R(1) = TBDMS) derived from adenosine and uridine was studied. The best results in respect of yield (56 to 81%) and diastereoselectivity (95:5 to >98:2) were obtained with a cerium reagent (RCcCl(2)).