3'-O-TBDMS-2'-O-methylAdo | 251297-02-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 3'-O-TBDMS-2'-O-methylAdo
• 英文别名: ((2R,3R,4R,5R)-5-(6-Amino-9H-purin-9-yl)-3-((tert-butyldimethylsilyl)oxy)-4-methoxytetrahydrofuran-2-yl)methanol；[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-[tert-butyl(dimethyl)silyl]oxy-4-methoxyoxolan-2-yl]methanol
• CAS: 251297-02-6
• 化学式: C₁₇H₂₉N₅O₄Si
• 分子量: 395.534
• InChiKey: GAEIWCZQQIBQRB-XNIJJKJLSA-N

物化性质

• 沸点：
  539.1±60.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  27.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  117.54
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  3'-O-TBDMS-2'-O-methylAdo 在 吡啶 、 硼氘化钠 、 2,2,6,6-四甲基哌啶氧化物 、 氘代甲醇-d 、 碘苯二乙酸 、 重水 、 potassium carbonate 、 二甲基亚砜 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 水 、 甲苯 、 乙腈 为溶剂， 反应 41.0h， 生成
  参考文献：
  名称：

  [EN] S-ANTIGEN TRANSPORT INHIBITING OLIGONUCLEOTIDE POLYMERS AND METHODS
  [FR] POLYMÈRES OLIGONUCLÉOTIDIQUES INHIBANT LE TRANSPORT DE L'ANTIGÈNE S ET MÉTHODES

  摘要：

  各种实施方式提供了STOPS™聚合物，这些聚合物是S-抗原转运抑制寡核苷酸聚合物，提供了制备它们的方法以及使用它们治疗疾病和症状的方法。在某些实施方式中，STOPS™修饰的寡核苷酸包括至少部分磷硫酸酯化的交替A和C单元序列，具有如本文所述的修饰。通过HBsAg分泌测定确定的STOPS™修饰的寡核苷酸对乙型肝炎的序列无关抗病毒活性，其EC50小于100 nM。

  公开号：

  WO2021119325A1
• 作为产物：
  描述：

  2'-O-甲基腺苷 在 吡啶 、 咪唑 、 水 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 19.5h， 生成 3'-O-TBDMS-2'-O-methylAdo
  参考文献：
  名称：

  Modified Short Interfering Nucleic Acid (siNA) Molecules and Uses Thereof

  摘要：

  本文披露了包含修饰核苷酸的短干扰核酸（siNA）分子及其用途。siNA分子可以是双链的，并包括从2'-O-甲基核苷酸和2'-氟核苷酸中选择的修饰核苷酸。本文还披露了包含（a）磷酸化阻断剂、共轭基团或5'-稳定端盖；以及（b）短干扰核酸（siNA）的siNA分子。

  公开号：

  US20220177888A1

文献信息

• Amide-Linked Ribonucleoside Dimers Derived from 5‘-Amino-5‘-deoxy- and 3‘-(Carboxymethyl)-3‘-deoxynucleoside Precursors¹
  作者：Matt A. Peterson、Bradley L. Nilsson、Sanchita Sarker、Bogdan Doboszewski、Weijian Zhang、Morris J. Robins

  DOI：10.1021/jo9908647

  日期：1999.10.1

  Treatment of tert-butyldimethylsilyl (TBDMS) derivatives of 3'-keto(adenosine or uridine) with [(ethoxycarbonyl)methylene]triphenylphosphorane gave exocyclic alkenes that underwent stereoselective hydrogenation to give 3'-deoxy-3'-[(ethoxycarbonyl)methyl](Ado or Urd) analogues. Saponification provided the 3'-(carboxymethyl)-3'-deoxy(Ado and Urd) derivatives 37 and 38. Treatment of 37 or 38 with DCC and 5'-amino-2',3'-bis-O-TBDMS-5'-deoxynucleosides gave the amide-linked dimers (74-82%). Activation of 37 or 38 with 4-nitrophenol/DCC, and direct coupling of the 4-nitrophenyl esters with 5'-amino-5'-deoxy(Ado or Urd) in pyridine also produced amide dimers efficiently (65-70%). Analogous activation of a 5'-O-DMT-protected carboxylate, and its coupling with 5'-amino-5'-deoxy-2'-O-methyladenosine gave the amide dimer in good yield (74%). Coupling (DCC) of a 5'-azido-2'-O-TBDMS-3'-(carboxymethyl)-3', 5'-dideoxyuridine intermediate with 5'-amino-5'-deoxynucleosides gave amide-linked dimers (72-78%) that can serve as masked (azide reduction) 5'-amino dimers for analogous synthesis of extended amide-linked oligomers.
• Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells
  作者：Fumihiro Ishikawa、Sho Konno、Hideaki Kakeya、Genzoh Tanabe

  DOI：10.3762/bjoc.20.39

  日期：——

  The adenylation (A) domain is essential for non-ribosomal peptide synthetases (NRPSs), which synthesize various peptide-based natural products, including virulence factors, such as siderophores and genotoxins. Hence, the inhibition of A-domains could attenuate the virulence of pathogens. 5’-O-N-(Aminoacyl or arylacyl)sulfamoyladenosine (AA-AMS) is a bisubstrate small-molecule inhibitor of the A-domains of NRPSs. However, the bacterial cell permeability of AA-AMS is typically a problem owing to its high hydrophilicity. In this study, we investigated the influence of a modification of 2′-OH in the AMS scaffold with different functional groups on binding to target enzymes and bacterial cell penetration. The inhibitor 7 with a cyanomethyl group at 2′-OH showed desirable inhibitory activity against both recombinant and intracellular gramicidin S synthetase A (GrsA) in the gramicidin S-producer Aneurinibacillus migulanus ATCC 9999, providing an alternative scaffold to develop novel A-domain inhibitors.
• [EN] PNPLA3-TARGETING SHORT INTERFERING RNA (SIRNA) MOLECULES AND USES THEREOF<br/>[FR] MOLÉCULES D'ARN INTERFÉRENT COURT (ARNSI) CIBLANT PNPLA3 ET LEURS UTILISATIONS
  申请人：[en]ALIGOS THERAPEUTICS, INC.

  公开号：WO2023034937A1

  公开（公告）日：2023-03-09

  Disclosed herein are short interfering RNA (siRNA) molecules that downregulate expression of PNPLA3 or variants thereof. The siRNA molecules comprise modified nucleotides and uses thereof. The siRNA molecules may be double stranded and comprise modified nucleotides, such as 2'-O-methyl nucleotides and 2'-fluoro nucleotides, and ligands.
• [EN] MODIFIED SHORT INTERFERING NUCLEIC ACID (SINA) MOLECULES AND USES THEREOF<br/>[FR] MOLÉCULES D'ACIDE NUCLÉIQUE INTERFÉRENT COURT MODIFIÉES (SINA) ET LEURS UTILISATIONS
  申请人：[en]ALIGOS THERAPEUTICS, INC.

  公开号：WO2023039076A1

  公开（公告）日：2023-03-16

  Disclosed herein are short interfering nucleic acid (siNA) molecules comprising modified nucleotides and uses thereof. The siNA molecules may be double stranded and comprise modified nucleotides selected from 2'-O-methyl nucleotides and 2'-fluoro nucleotides. Further disclosed herein are siNA molecules comprising additional modification including a phosphorylation blocker, conjugated moiety, or 5'-stabilized end cap. The siNA molecules may reduce or inhibit the production of hydroxysteroid dehydrogenase.