5'-(O-tert-butyl(dimethyl)silyl)-3'-ketothymidine | 147043-60-5

• 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: 5'-(O-tert-butyl(dimethyl)silyl)-3'-ketothymidine
• 英文别名: 1-[(2R,5R)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-oxooxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 147043-60-5
• 化学式: C₁₆H₂₆N₂O₅Si
• 分子量: 354.478
• InChiKey: VPDRTDFVZCJBSM-CHWSQXEVSA-N

物化性质

• 密度：
  1.143±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.72
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5'-(O-tert-butyl(dimethyl)silyl)-3'-ketothymidine 在 盐酸 、 copper(l) iodide 、 18-冠醚-6 作用下， 以 二氯甲烷 为溶剂， 反应 82.0h， 生成 1-(3-C-(1,1-dimethylpropanoyl)-2-deoxy-β-D-threo-pentofuranosyl)thymine
  参考文献：
  名称：

  C-3‘-Branched Thymidines as Precursors for the Selective Generation of C-3‘-Nucleoside Radicals

  摘要：

  C-3'-nucleoside radicals can be generated via Norrish type I photocleavage of C-3'-acyl nucleoside derivatives. In monomer experiments employing C-3'-acylthymidine derivatives 2 and 3, a 1:1 mixture of isomers of the H-abstraction products was obtained when the photolysis was carried out in the presence of a hydrogen donor. Derivatives 2 were synthesized by an approach which involves the formation of a silyl-protected cyanohydrin, which is subsequently alkylated with organolithium reagents, followed by hydrolysis. Derivatives 3 could be obtained via a multistep synthesis starting from diol 7. Several different methods were attempted to oxidize the unprotected diol to the alpha-hydroxy aldehyde. Finally, a route was chosen which involves a protection-deprotection sequence followed by oxidation of the free primary alcohol. The resulting modified nucleosides should facilitate the study of C-3'-DNA radicals.

  DOI：

  10.1021/jo982022y
• 作为产物：
  描述：

  5’-O-(叔丁基二甲基甲硅烷基)胸苷 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以80%的产率得到5'-(O-tert-butyl(dimethyl)silyl)-3'-ketothymidine
  参考文献：
  名称：

  五氯化磷促进了2'-和3'-脱氧核苷的宝石二氯化。

  摘要：

  规范核苷各个位置的卤素取代产生了许多生物活性结构变体。本文中，提出了两个独特的带有宝石二氯基团的糖修饰的核苷系列的合成。合成计划要求将五氯化磷受控添加到适当保护的2'-或3'-酮脱氧核苷中间体中作为关键步骤，以促进此类功能化分子的快速构建。在相同的反应条件下，形成2'，2'-dichloro-2'，3'-二脱氧核苷的化学选择性最高，而在3'的情况下发生竞争性2'，3'-消除过程，3'-二氯对应物。

  DOI：

  10.3390/molecules23061457

文献信息

• [EN] SYNTHESIS OF 3'N NUCLEOSIDES THROUGH OXIME INTERMEDIATES AND RELATED COMPOUNDS<br/>[FR] SYNTHÈSE DE 3'N NUCLÉOSIDES AU MOYEN D'INTERMÉDIAIRES D'OXIME ET DE COMPOSÉS APPARENTÉS
  申请人：JANSSEN BIOPHARMA INC

  公开号：WO2021186328A1

  公开（公告）日：2021-09-23

  Provided herein are novel synthetic routes to amines through an oxime intermediate, e.g., 3'-N nucleosides and novel and intermediate compounds produced during these synthetic procedures.

  本文提供了一种通过肟中间体合成胺类化合物的新颖方法，例如3'-N核苷和在这些合成过程中产生的新颖和中间化合物。
• Cerium(III) Chloride-Mediated Reactions of Sulfonamide Dianions
  作者：David C. Johnson、Theodore S. Widlanski

  DOI：10.1021/jo034001w

  日期：2003.6.1

  5'-aldehyde, 3'-ketouridine, and 3'-ketothymidine. The reaction was chemoselective for aldehydes in the presence of nitriles. Acetoxy groups are labile and thus not suitable protecting groups for alcohols under these conditions. N-Benzyl-alpha, N-dilithio methanesulfonamide was found to be of sufficient basicity to cause enolate formation with sensitive substrates, such as 1-phenylacetone. However, the

  本文介绍的是氯化铈（III）介导高产量以及通常非对映选择性地将N-苄基-α，N-二硫代甲磺酰胺加到具有重要生物意义的醛和酮中的能力的第一份报告。对碱敏感的底物，例如Fmoc保护的丙氨酸，柠檬醛，5-胆甾烯-3-酮，尿苷5'-醛，3'-酮胍和3'-酮基吡啶，进行平滑添加。在腈存在下，该反应对醛具有化学选择性。乙酰氧基不稳定，因此在这些条件下不适合作为醇的保护基。发现N-苄基-α，N-二硫代甲烷磺酰胺具有足够的碱性，以引起与敏感底物例如1-苯基丙酮的烯醇化物形成。然而，在这些情况下，氯化铈（III）的加入介导了二价阴离子的碱性并抑制了烯醇化物的形成。另外，铈（III）具有将各种N-脂族/芳族甲磺酰胺二价阴离子加到3'-酮胍中的一般用途。
• Anti-HIV Derivatives of 1-(2,3-Dideoxy-3-<i>N</i>-hydroxyamino-β-D-<i>threo</i>-pentofuranosyl)thymine
  作者：Jean M. J. Tronchet、Martina Zsély、Karel Capek、Istvan Komaromi、Michel Geoffroy、Erik De Clercq、Jan Balzarini

  DOI：10.1080/15257779408010670

  日期：1994.9

  Representative examples of the title compounds including bicyclic analogs (7-9) in which a perhydro-1,3-oxazine is ortho-fused to the furanose ring, have been prepared in good to excellent yields. Compounds 5 and 7 showed marked activity against HIV-1 and HIV-2 replication in CEM cells (50% inhibitory concentration: 0.80-4.3 mu g/mL). Their di-O-acetylated (6) and mono-O-acetylated (8) derivatives were considerably less effective. To the best of our knowledge, these beta-D-threo anti-HIV nucleoside analogs constitute the first examples of anti-HIV active nucleosides bearing this configuration.
• 3'-C-Hydroxymethylthymidine: Synthesis and Incorporation into Oligodeoxynucleotide Analogues
  作者：Pia Nøncgaard Jørgensen、Margit Svendsen、Claus Nielsen、Jesper Wengel

  DOI：10.1080/15257779508012502

  日期：1995.5.1

  The stereoselective synthesis of 3'-C-hydroxymethylthymidine (5) in five steps from thymidine has been accomplished and this nucleoside has been incorporated into oligodeoxynucleotides (ODNs) in different ways.
• Synthesis of Novel 3′-<i>C</i>-(Hydroxymethyl)thymidines and Oligodeoxynucleotide Analogues Containing Compressed 3′-<i>C</i>-Hydroxymethyl-Linked Phosphodiester Backbones
  作者：Jesper Wengel、Margit L. Svendsen、Pia N. J⊘rgensen、Claus Nielsen

  DOI：10.1080/15257779508009485

  日期：1995.9

  Lombardo methylenation of the novel 2'-deoxy-3'-ketonucleosides 4 afforded 2',3'-dideoxy-3'-C-methylene nucleosides 5, which were subjected to catalytic dihydroxylation reactions. In the case of 5'-deoxynucleoside 5a, a 1:1 mixture of 3'-C-hydroxymethyl diastereoisomers 6a and 7a was obtained, whereas the 5'-O-silylated nucleoside 5b afforded 3'-C-(hydroxymethyl)thymidine derivative 6b as the only product. Sharpless asymmetric dihydroxylation of 5a proceeded in low yield to give 5a and 7a as a 10:3 mixture. 5'-O-Silylated nucleoside 6b was converted into the phosphoramidite synthon 9, which was applied in automated syntheses of oligodeoxynucleotides containing novel compressed 3'-C-hydroxymethyl-linked phosphodiester backbones.