2',3'-O-Isopropyliden-5'-desoxy-5'-ioduridin | 14671-65-9

• 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: 2',3'-O-Isopropyliden-5'-desoxy-5'-ioduridin
• 英文别名: Uridine, 5'-deoxy-5'-iodo-2',3'-O-(1-methylethylidene)-；1-[(3aR,4R,6S,6aS)-6-(iodomethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]pyrimidine-2,4-dione
• CAS: 14671-65-9
• 化学式: C₁₂H₁₅IN₂O₅
• 分子量: 394.166
• InChiKey: PSNGXFJVSKFMNY-PEBGCTIMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2',3'-O-Isopropyliden-5'-desoxy-5'-ioduridin 在 盐酸 、 乙二醇乙醚 、 silver tribenzyldiphosphate 、 lithium chloride 、 苯 作用下， 生成 尿苷-5’-二磷酸
  参考文献：
  名称：

  Anand et al., Journal of the Chemical Society, 1952, p. 3665,3666, 3668

  摘要：

  DOI：
• 作为产物：
  描述：

  2',3'-O-isopropylidene-5'-O-tosyluridine 在 丙酮 、 sodium iodide 作用下， 生成 2',3'-O-Isopropyliden-5'-desoxy-5'-ioduridin
  参考文献：
  名称：

  Levene; Tipson, Journal of Biological Chemistry, 1934, vol. 106, p. 113,115, 118

  摘要：

  DOI：

文献信息

• Synthesis and oligomerization of cysteinyl nucleosides
  作者：Miklós Bege、Ilona Bereczki、Dénes J. Molnár、Máté Kicsák、Krisztina Pénzes-Daku、Zsuzsanna Bereczky、Györgyi Ferenc、Lajos Kovács、Pál Herczegh、Anikó Borbás

  DOI：10.1039/d0ob01890b

  日期：——

  for oligomerization, in order to produce new types of synthetic nucleic acids. We elaborated different strategies for the synthesis of cysteinyl nucleosides as monomers of cysteinyl nucleic acids using nucleophilic substitution or thiol–ene coupling as a synthetic tool, and utilised on two complementary nucleosides, uridine and adenosine. Dipeptidyl dinucleosides and pentameric cysteinyl uridine were

  已知核苷和核酸类似物具有相当大的治疗潜力。在这项工作中，通过将半胱氨酸与核苷偶联，我们成功合成了化合物，这些化合物不仅单体形式具有有趣的生物学特性，而且还可以用于寡聚化，以生产新型合成核酸。我们使用亲核取代或硫醇-烯偶联作为合成工具，阐述了合成半胱氨酰核苷作为半胱氨酰核酸单体的不同策略，并利用了两个互补的核苷，尿苷和腺苷。由单体结构单元制备二肽基二核苷和五聚半胱氨酰尿苷，
• Preparation, antibacterial effects and enzymatic degradation of 5-fluorouracil nucleosides
  作者：Beatrice Schwarz、Dieter Cech、Antonín Holý、Jan Škoda

  DOI：10.1135/cccc19803217

  日期：——

  Reaction of perbenzoylated aldopentafuranosyl derivatives of uracil with fluorine in acetic acid afforded perbenzoylated 5-fluorouracil nucleosides. Their methanolysis gave the following free nucleosides of 5-fluorouracil: β-D-ribofuranoside (Id), 2-deoxy-β-D-ribofuranoside (IId), their enantiomers VIII and IX, α-D-ribofuranoside (XIII), 2-deoxy-α-D-ribofuranoside (XV), β-D-arabinofuranoside (IV) and its L-enantiomer X, β-D-xylofuranoside (V) and its α-D-anomer XI, α-L-lyxofuranoside (VI) and 2-deoxy-α-L-lyxofuranoside (VII) and the enantiomers of the latter two compounds, XII and XIV, respectively. Analogously were obtained 5-deoxy-β-D-ribofuranoside (III), β-D-ribopyranoside (XVI) and 1-(S)-(2,3-dihydroxypropyl)-5-fluorouracil (XVIIc). 1-Allyl-5-fluorouracil (XVIII) was prepared by reaction of allyl bromide with 2,4-bis(trimethylsilyloxy)-5-fluoropyrimidine. The cell-free extract from Escherichia coli cleaves all the 5-fluorouracil nucleosides in which the nucleoside carbon atom has the R-configuration and the 3'-hydroxyl of the sugar moiety is in trans-relation to the base. Compounds which have not these structural features are resistant. Besides nucleosides which on enzymatic cleavage afford 5-fluorouracil, also the non-cleavable 1-(2-deoxy-β-L-ribofuranosyl)-5-fluorouracil (IX), 1-(2-deoxy-α-D-ribofuranosyl)-5-fluorouracil (XV) and 1-(2-deoxy-α-D-lyxofuranosyl)-5-fluorouracil (XIV) exhibit an antibacterial effect towards E. coli (ID₅₀ 1.0-2.5 . 10^-5 M). This effect can be reversed by 2'-deoxyuridine but not by thymidine.

  在冰乙酸中，尿嘧啶的苄酰化醛基五糖衍生物与氟反应生成了苄酰化的5-氟尿嘧啶核苷。它们的甲醇解产生了以下的游离5-氟尿嘧啶核苷：β-D-核糖呋喃苷（Id）、2-脱氧-β-D-核糖呋喃苷（IId）、它们的对映异构体VIII和IX、α-D-核糖呋喃苷（XIII）、2-脱氧-α-D-核糖呋喃苷（XV）、β-D-阿拉伯呋喃苷（IV）及其L-对映体X、β-D-木糖呋喃苷（V）及其α-D-异构体XI、α-L-吕糖呋喃苷（VI）和2-脱氧-α-L-吕糖呋喃苷（VII）以及后两种化合物的对映体XII和XIV。类似地获得了5-脱氧-β-D-核糖呋喃苷（III）、β-D-核糖吡喃苷（XVI）和1-(S)-(2,3-二羟基丙基)-5-氟尿嘧啶（XVIIc）。1-丙烯基-5-氟尿嘧啶（XVIII）是通过丙烯基溴和2,4-双(三甲基硅氧基)-5-氟嘧啶反应制备的。大肠杆菌的细胞提取物可裂解所有5-氟尿嘧啶核苷，其中核苷碳原子具有R-构型，糖基的3'-羟基与碱基呈反式关系。不具备这些结构特征的化合物是抗性的。除了在酶解时产生5-氟尿嘧啶的核苷外，还有不可裂解的1-(2-脱氧-β-L-核糖呋喃基)-5-氟尿嘧啶（IX）、1-(2-脱氧-α-D-核糖呋喃苷)-5-氟尿嘧啶（XV）和1-(2-脱氧-α-D-吕糖呋喃苷)-5-氟尿嘧啶（XIV）对大肠杆菌表现出抗菌作用（ID50为1.0-2.5 x 10^-5 M）。这种效应可以被2'-脱氧尿苷而不是胸苷逆转。
• 17O NMR of nucleosides. 3—Chemical shifts of substituted uridines and ribothymidines
  作者：Herbert M. Schwartz、Malcolm Maccoss、Steven S. Danyluk

  DOI：10.1002/mrc.1260231102

  日期：1985.11

  acetonitrile and aqueous solvents. The solvent shift differences between acetonitrile and water at O‐4 (30–42 ppm) and O‐2 (13–16 ppm) vary significantly from each other, but the chemical shift changes induced by changing the substituent at C‐5 correlated well only with the O‐4 shifts and the electron‐withdrawing ability of the substituent. Examination of the 17O shifts of model compounds reconfirms the predominance

  在乙腈和水性溶剂中，通过 17O NMR 研究了在 C-5 处带有不同取代基并在 O-4 和 O-2 羰基中富含 17O（Ca50%）的尿苷和核糖苷衍生物。乙腈和水在 O-4 (30-42 ppm) 和 O-2 (13-16 ppm) 处的溶剂位移差异彼此显着不同，但改变 C-5 取代基引起的化学位移变化相关性很好仅具有 O-4 位移和取代基的吸电子能力。对模型化合物的 17O 位移的检查再次证实了两种羰基的酮互变异构体的优势。关于核苷碱基王的电子结构和羰基的氢键能力，讨论了溶剂位移和取代基位移的重要性。
• Synthesis of novel deoxynucleoside S-methylphosphonic acids using S-(diisopropylphosphonomethyl)isothiouronium tosylate, a new equivalent of mercaptomethylphosphonate
  作者：Ivana Kóšiová、Miloš Buděšínský、Natalya Panova、Ivan Rosenberg

  DOI：10.1039/c0ob00738b

  日期：——

  The synthesis of the novel nucleotide analogues 5′-deoxynucleoside-5′-S-methylphosphonates, starting from 5′-deoxy-5′-haloribonucleosides, 5′-O-tosylribonucleosides, and 2′-O-triflylnucleosides, is described. The phosphonothiolation of these compounds was achieved using S-(diisopropylphosphonomethyl)isothiouronium tosylate, a new, odourless, and efficient equivalent of mercaptomethylphosphonate. The thiolate anion of mercaptomethylphosphonate was generated in situ from the isothiouronium salt in both protic and aprotic solvents using two equivalents of sodium iso-propoxide. The prepared nucleoside 5′-S-methylphosphonates were deprotected, and the free phosphonic acids were transformed into diphosphoryl derivatives (the NTP analogues). Both mononucleotides and NTP analogues were studied as substrates/inhibitors of several enzymes that are involved in the nucleoside/nucleotide metabolism.

  本文介绍了从 5′-脱氧-5′-卤代核苷、5′-O-对甲苯磺酸核苷和 2′-O-三氟甲基核苷出发，合成新型核苷酸类似物 5′-脱氧核苷-5′-S-甲基膦酸盐。这些化合物的硫代磷酸化是使用 S-（二异丙基膦酰甲基）异硫脲对甲苯磺酸盐（一种新型、无味、高效的巯基甲基膦酸盐等效物）实现的。巯甲基膦酸硫代阴离子是在原生态和非原生态溶剂中使用两个等量的异丙醇钠从异硫脲盐原位生成的。制备的核苷 5′-S-甲基膦酸盐经脱保护后，游离的膦酸转化为二磷酸衍生物（NTP 类似物）。研究人员将单核苷酸和 NTP 类似物作为参与核苷/核苷酸代谢的几种酶的底物/抑制剂。
• [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。