8-bromo-2',3',5'-(triOTMS)adenosine | 60091-08-9

• 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: 8-bromo-2',3',5'-(triOTMS)adenosine
• 英文别名: 9-[(2R,3R,4R,5R)-3,4-bis(trimethylsilyloxy)-5-(trimethylsilyloxymethyl)oxolan-2-yl]-8-bromopurin-6-amine
• CAS: 60091-08-9
• 化学式: C₁₉H₃₆BrN₅O₄Si₃
• 分子量: 562.686
• InChiKey: PNLNNAJUWMYZPM-SCFUHWHPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.36
• 重原子数：
  32.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  106.54
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  8-bromo-2',3',5'-(triOTMS)adenosine 在 ammonium hydroxide 、 sodium naphthalenide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.5h， 生成 腺苷
  参考文献：
  名称：

  用萘钠有效去除嘌呤核苷中的糖O-甲苯磺酰基和杂环卤素

  摘要：

  萘二甲酸钠可去除糖中的2 '-，3'-或5'- O-甲苯磺酰基，并去除嘌呤核苷中的2-，6-或8-卤素。开发了一种改进的甲苯磺酰基保护策略，用于从2'，5'-二-O-甲苯磺酰基腺苷合成9-（3-脱氧-3-氟-β-D-木呋喃糖基）腺嘌呤。

  DOI：

  10.1016/s0040-4020(97)00313-x
• 作为产物：
  描述：

  三甲基氯硅烷 、 8-溴膘苷 在 吡啶 作用下， 反应 0.5h， 生成 8-bromo-2',3',5'-(triOTMS)adenosine
  参考文献：
  名称：

  用萘钠有效去除嘌呤核苷中的糖O-甲苯磺酰基和杂环卤素

  摘要：

  萘二甲酸钠可去除糖中的2 '-，3'-或5'- O-甲苯磺酰基，并去除嘌呤核苷中的2-，6-或8-卤素。开发了一种改进的甲苯磺酰基保护策略，用于从2'，5'-二-O-甲苯磺酰基腺苷合成9-（3-脱氧-3-氟-β-D-木呋喃糖基）腺嘌呤。

  DOI：

  10.1016/s0040-4020(97)00313-x

文献信息

• Antiviral activity of C-alkylated purine nucleosides obtained by cross-coupling with tetraalkyltin reagents
  作者：Arthur A. Van Aerschot、Petros Mamos、Nancy J. Weyns、Satoru Ikeda、Erik De Clercq、Piet A. Herdewijn

  DOI：10.1021/jm00072a013

  日期：1993.10

  2-, 6-, And 8-alkylated (methyl, ethyl, and vinyl) adenosine analogues were synthesized by a palladium-catalyzed cross-coupling of a tetraalkyltin with the halogenated purine nucleosides. The synthesis of the 8-substituted analogues was accomplished using a transient protection procedure. The 6-alkylated-9-beta-D-ribofuranosylpurines as well as 2-ethyladenosine were cytotoxic at relatively low concentrations

  通过将四烷基锡与卤代嘌呤核苷进行钯催化的交叉偶联，可合成2-，6-和8-烷基化（甲基，乙基和乙烯基）的腺苷类似物。8-取代类似物的合成使用瞬态保护程序完成。6烷基化的9-β-D-呋喃呋喃糖基嘌呤以及2-乙基腺苷在相对较低的浓度（0.8-10微克/ mL）下具有细胞毒性。8-甲基腺苷是牛痘病毒的有效和选择性抑制剂，而8-乙基和8-乙烯基腺苷对呼吸道合胞病毒具有特异性抑制作用。8-Vinyladenosine显示出对单纯疱疹病毒（1型）的特殊活性。
• Discovery of new S-adenosylmethionine decarboxylase inhibitors for the treatment of Human African Trypanosomiasis (HAT)
  作者：Bradford Hirth、Robert H. Barker、Cassandra A. Celatka、Jeffrey D. Klinger、Hanlan Liu、Bakela Nare、Amarjit Nijjar、Margaret A. Phillips、Edmund Sybertz、Erin K. Willert、Yibin Xiang

  DOI：10.1016/j.bmcl.2009.04.096

  日期：2009.6

  Modification of the structure of trypanosomal AdoMetDC inhibitor 1 (MDL73811) resulted in the identification of a new inhibitor 7a, which features a methyl substituent at the 8-position. Compound 7a exhibits improved potencies against both the trypanosomal AdoMetDC enzyme and parasites, and better blood brain barrier penetration than 1. (C) 2009 Published by Elsevier Ltd.
• Synthèe, caractérisation et propriétés cytotoxiques des premiers ‘métallocénonucléosides’
  作者：P Meunier、I Ouattara、B Gautheron、J Tirouflet、D Camboli、J Besançon

  DOI：10.1016/0223-5234(91)90070-4

  日期：1991.4

  The synthesis of the first 'metallocenonucleosides' (nucleosides containing a metallocenic moiety in their framework) of the formula Ns-C = C-Fc, Ns-CH = CH-Fc and Ns-CH2-CH2-Fc (Ns = uridine, deoxyuridine, adenosine; Fc: C5H4FeC5H5) has been conducted in the presence of palladium salt according to the following routes: i) reaction of a 5-chloromercuri-nucleoside on ethynylferrocene; ii) hydrozirconation (Schwartz' reagent) of ethynylferrocene followed by the reaction of a 5-halogeno nucleoside; iii) direct coupling between ethynylferrocene and a 5-halogeno nucleoside. The same procedures allowed the synthesis of the corresponding 'metallocenonucleobases' Nb-C = C-Fc, Nb-CH = CH-Fc and NbCH2CH2Fc (Nb = uracil, cytosine, adenine) which have also been prepared by acid solvolysis of the nucleosides precursors. The compounds obtained were purified by HPLC technique and were characterized by H-1 NMR and mass spectrometry. The cytotoxicity in vitro has been studied on L 1210 cells. Only modest activity has been observed.
• RlmN and Cfr are Radical SAM Enzymes Involved in Methylation of Ribosomal RNA
  作者：Feng Yan、Jacqueline M. LaMarre、Rene Röhrich、Jochen Wiesner、Hassan Jomaa、Alexander S. Mankin、Danica Galonić Fujimori

  DOI：10.1021/ja910850y

  日期：2010.3.24

  Posttranscriptional modifications of ribosomal RNA (rRNA) nucleotides are a common mechanism of modulating the ribosome's function and conferring bacterial resistance to ribosome-targeting antibiotics. One such modification is methylation of an adenosine nucleotide within the peptidyl transferase center of the ribosome mediated by the endogenous methyltransferase RImN and its evolutionarily related resistance enzyme Cfr. These methyltransferases catalyze methyl transfer to aromatic carbon atoms of the adenosine within a complex 23S rRNA substrate to form the 2,8-dimethylated product. RImN and Cfr are members of the Radical SAM superfamily and contain the characteristic cysteine-rich CX3CX2C motif. We demonstrate that both enzymes are capable of accommodating the requisite [4Fe-4S] cluster. S-Adenosylmethionine (SAM) is both the methyl donor and the source of a 5'-deoxyadenosyl radical, which activates the substrate for methylation. Detailed analyses of the rRNA requirements show that the enzymes can utilize protein-free 23S rRNA as a substrate, but not the fully assembled large ribosomal subunit, suggesting that the methylations take place during the assembly of the ribosome. The key recognition elements in the 23S rRNA are helices 90-92 and the adjacent single stranded RNA that encompasses A2503. To our knowledge, this study represents the first in vitro description of a methyl transfer catalyzed by a member of the Radical SAM superfamily, and it expands the catalytic repertoire of this diverse enzyme class. Furthermore, by providing information on both the timing of methylation and its substrate requirements, our findings have important implications for the functional consequences of Cfr-mediated modification of rRNA in the acquisition of antibiotic resistance.