1-(5-O-tert-butyldimethylsilyl-2-deoxy-2-fluoro-β-D-ribofuranosyl)uracil | 122757-48-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 1-(5-O-tert-butyldimethylsilyl-2-deoxy-2-fluoro-β-D-ribofuranosyl)uracil
• 英文别名: 2'-fluoro-5'-tert-butyldimethylsilyl 2'-deoxyuridine；5'-O-TBDMS-2'-deoxy-2'-fluorouridine；TBDMS(-5)Ribf2F(b)-uracil-1-yl；1-[(2R,3R,4R,5R)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-3-fluoro-4-hydroxyoxolan-2-yl]pyrimidine-2,4-dione
• CAS: 122757-48-6
• 化学式: C₁₅H₂₅FN₂O₅Si
• 分子量: 360.458
• InChiKey: DYFZTUHXHLQLAT-OJAKKHQRSA-N

物化性质

• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.15
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  88.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(5-O-tert-butyldimethylsilyl-2-deoxy-2-fluoro-β-D-ribofuranosyl)uracil 在 吡啶 、 chromium(VI) oxide 、 盐酸羟胺 、 乙酸酐 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 1-[(E/Z)-2',3'-dideoxy-2'-fluoro-3'-(hydroxyimino)-5'-OTBDMS-β-D-erythro-pentofuranosyl]uracil
  参考文献：
  名称：

  2',3'-Dideoxy-2'-fluoro-3'-(hydroxyimino)-、-3'-(甲氧基亚氨基)-和-3'-(羟基氨基)嘧啶核苷的合成

  摘要：

  合成了新系列的 2',3'-dideoxy-2'-fluoro-3'-(羟基亚氨基)-、-3'-(甲氧基亚氨基)-和-3'-(羟基氨基)嘧啶核苷。作为 (E) 和 (Z) 异构体不可分离的混合物获得的前两种衍生物的结构分配基于 1 H 和 19 F NMR 光谱分析。特别是，我们观察到 19F NMR 光谱的显着差异，这是由具有近邻氮（肟）和氟原子的化合物通过空间 N-F 耦合引起的，其中孤对原子正确定向以重叠。评估了靶核苷的抗病毒和细胞毒活性；然而，它们都没有表现出任何抗病毒活性。只有 2',3'-dideoxy-2'-fluoro-3'-(hydroxyamino)cytidine (19) 对鼠白血病细胞 (L1210) 的增殖显示出中等活性。

  DOI：

  10.1002/ejoc.201200119
• 作为产物：
  描述：

  叔丁基二甲基氯硅烷 、 2'-氟-2'-脱氧尿苷 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以67%的产率得到1-(5-O-tert-butyldimethylsilyl-2-deoxy-2-fluoro-β-D-ribofuranosyl)uracil
  参考文献：
  名称：

  脑靶向的1-（2-脱氧-2-氟-β-D-呋喃呋喃糖基）-（E）-5-（2-碘乙烯基）尿嘧啶与二氢吡啶<->吡啶鎓盐氧化还原化学传递的合成系统。

  摘要：

  在THF中存在（Ph3P）2Pd2（II）Cl2的条件下与（E）-Bu（3）Sn-CH = CH-SiMe（3）偶联，得到1- [2-脱氧-2-氟-3-O- （3-吡啶基羰基）-β-D-呋喃呋喃糖基]-（E）-5-（2-三甲基甲硅烷基乙烯基）尿嘧啶。用碘甲烷在丙酮中进行季铵化，得到N-甲基碘化碘盐。用一锅法在乙腈中用单氯化碘在乙腈中电离反应性（E）-三甲基甲硅烷基乙烯基部分，并用连二亚硫酸钠在碘化季铵盐上重合碘化季铵盐。 -2-氟-3-O-（1-甲基-1,4-二氢吡啶基-3-羰基）-β-D-呋喃呋喃糖基]-（E）-5-（2-碘乙烯基）尿嘧啶（IVFRU-CDS） 。这种合成策略易于接受IVFRU的高比活度放射性碘化。

  DOI：

  10.1016/0008-6215(93)84064-d

文献信息

• [EN] NUCLEIC ACID-POLYPEPTIDE COMPOSITIONS AND USES THEREOF<br/>[FR] COMPOSITIONS D'ACIDE NUCLÉIQUE-POLYPEPTIDE ET UTILISATIONS DE CELLES-CI
  申请人：AVIDITY BIOSCIENCES LLC

  公开号：WO2019071028A1

  公开（公告）日：2019-04-11

  Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a modified polynucleic acid molecule and a polymer. Also described herein include methods for treating a cancer which utilize a composition or a pharmaceutical formulation comprising a binding moiety conjugated to a polynucleic acid molecule and a polymer.

  本文披露了包含与修饰的多核苷酸分子和聚合物结合基团的组合物和药物配方。本文还描述了利用包含与多核苷酸分子和聚合物结合基团共轭的组合物或药物配方治疗癌症的方法。
• STABILIZED NUCLEOTIDES FOR MEDICAL TREATMENT
  申请人：Deshpande Milind

  公开号：US20160016986A1

  公开（公告）日：2016-01-21

  5′-Deuterated nucleosides and nucleotides and modifications thereof are provided for use in medical therapies, including as antiviral, anti-tumor and anti-neoplastic agents. In one embodiment, compounds, methods and uses are provided for the treatment of hepatitis C, RSV, HSV and other viral diseases in a host, including a human.

  提供了用于医疗疗法的5'-氘代核苷和核苷酸以及其修饰，包括作为抗病毒、抗肿瘤和抗肿瘤剂。在一个实施例中，提供了化合物、方法和用途，用于治疗丙型肝炎、RSV、HSV和其他病毒性疾病在宿主中，包括人类。
• [EN] 2-HYDROXYIMINOPYRIMIDINE NUCLEOSIDES AND DERIVITIVES AND ANTIVIRAL USES THERETO<br/>[FR] NUCLÉOSIDES ET DÉRIVÉS DE 2-HYDROXYIMINOPYRIMIDINE ET UTILISATIONS ANTIVIRALES DE CEUX-CI
  申请人：SINCE & TECH DEVELOPMENT FUND AUTHORITY

  公开号：WO2022008025A1

  公开（公告）日：2022-01-13

  Disclosed herein are nucleosides and nucleotides analogs, methods for preparing the same, and methods for treating and/or ameliorating infection caused by a Coronaviridae virus, a Caliciviridae virus, an Orthomyxoviridae virus, a Herpesviridae virus, a Flaviviridae virus, a Filoviridae virus,and a Pneumoviridae virus with one or more nucleoside and nucleotide analogs of formula I. In certain embodiments, compounds and compositions of nucleoside or nucleotide derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are according to Formula (I): or a pharmaceutically acceptable salt, solvate, stereoisomeric form, a tautomeric form or polymorphic form thereof, wherein R1, R2, R3, R4, X, and sugar are as described herein.

  本文披露了核苷和核苷酸类似物，制备它们的方法，以及使用一种或多种公式I的核苷和核苷酸类似物治疗和/或改善由冠状病毒科病毒、钙病毒科病毒、流感病毒科病毒、疱疹病毒科病毒、黄病毒科病毒、丝状病毒科病毒和肺病毒科病毒引起的感染的方法。在某些实施例中，披露了核苷或核苷酸衍生物的化合物和组成物，可以单独或与其他抗病毒药物组合给予。在某些实施例中，化合物符合以下公式(I)：或其药用可接受的盐、溶剂化合物、立体异构体形式、互变异构体形式或多形形式，其中R1、R2、R3、R4、X和糖如本文所述。
• 一种核苷修饰物的制备方法
  申请人：上海兆维科技发展有限公司

  公开号：CN113549121B

  公开（公告）日：2023-05-02

  本发明公开一种核苷修饰物的制备方法。所述方法包括：使2’‑氟‑2’‑脱氧尿苷与氯硅烷试剂混合，反应得到2’‑氟‑5’‑叔丁基二甲基甲硅烷基2’‑脱氧尿苷，将其与二甲氧基三苯基氯甲烷混合，反应得到2’‑氟‑3’‑(双(4‑甲氧基苯基)(苯基)甲氧基)5’‑叔丁基二甲基甲硅烷基2’‑脱氧尿苷，再使其脱硅烷保护，得到2’‑氟‑3’‑(双(4‑甲氧基苯基)(苯基)甲氧基)2’‑脱氧尿苷，再将此脱氧尿苷与丁二酸酐经酰化反应得到5’‑丁二酰基‑2’‑氟‑3’‑(双(4‑甲氧基苯基)(苯基)甲氧基)2’‑脱氧尿苷，然后与三乙胺混合，反应得到结构式1所示的核苷修饰物。
• Nucleic Acid Related Compounds. 91. Biomimetic Reactions Are in Harmony with Loss of 2‘-Substituents as Free Radicals (Not Anions) during Mechanism-Based Inactivation of Ribonucleotide Reductases. Differential Interactions of Azide, Halogen, and Alkylthio Groups with Tributylstannane and Triphenylsilane¹
  作者：Morris J. Robins、Stanislaw F. Wnuk、Amelia E. Hernández-Thirring、Mirna C. Samano

  DOI：10.1021/ja962117m

  日期：1996.1.1

  The initial step in the mechanism-based inactivation of ribonucleotide reductases by 2'-chloro-2'-deoxynucleotides is abstraction of H3' by a proximal free radical on the enzyme. The C3' radical is postulated to undergo spontaneous loss of chloride, and the resulting cationic radical loses a proton to give a 3'-keto intermediate. Successive beta-eliminations produce a Michael acceptor which causes inactivation. This hypothesis would predict rapid loss of mesylate or tosylate anions from C2', but sluggish loss of azide or thiomethoxide. in contrast, loss of azido and methylthio radicals from C2' should occur readily whereas homolysis to give (methyl or tolylsulfonyl)oxy and fluoro radicals should be energetically prohibitive. Protected 3'-O-(phenoxythiocarbonyl)-2'-substitute nucleosides were treated with tributylstannane/AIBN or triphenylsilane/dibenzoyl peroxide in refluxing toluene. The 2'-O-(mesyl and tosyl) and 2'-fluoro compounds underwent direct radical-mediated hydrogenolysis of the thionocarbonate group to give 3'-deoxy-2'-substituted products, whereas 2'-(azido, bromo, chloro, iodo, and methylthio)-3'-thionocarbonates gave 2',3'-didehydro-2',3'-dideoxy derivatives via loss of 2'-substituents from an incipient C3' radical. These results are in harmony with loss of radicals, but not anions, from C2'. The well-known radical-mediated hydrogenolytic cleavage of halogen and methylthio (slow) groups from C2' of the S'-hydroxy (unprotected) precursors and reduction of 2'-azides to amines occurred with tributylstannane/AIBN. Triphenylsilane/dibenzoyl peroxide gave parallel (but slower) hydrogenolysis with the 2'-(iodo, bromo, and methylthio) compounds, but cleavage of the 2'-chloro group was very slow and no reduction of 2'-azides to amines was detected. Rather, the latter system effected slow hydrogenolytic removal of the 2'-azido group. Thus, chemoselective differentiation of certain functional groups is possible with triphenylsilane and tributylstannane. Reduction of azides to amines with tributylstannane is known, but hydrogenolytic deazidation (slow) with triphenylsilane in the absence of amine formation appears to be novel.