5'-O-(tert-butyldimethylsilyl)-2'-deoxyadenosine | 51549-30-5

• 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: 5'-O-(tert-butyldimethylsilyl)-2'-deoxyadenosine
• 英文别名: Adenosine, 2'-deoxy-5'-O-[(1,1-dimethylethyl)dimethylsilyl]-；(2R,3S,5R)-5-(6-aminopurin-9-yl)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-3-ol
• CAS: 51549-30-5
• 化学式: C₁₆H₂₇N₅O₃Si
• 分子量: 365.508
• InChiKey: HGLRBQHXIBHZTD-QJPTWQEYSA-N

物化性质

• 熔点：
  125-126 °C
• 沸点：
  529.1±60.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO：100 mg/mL（273.60 mM；需要超声）

计算性质

• 辛醇/水分配系数(LogP)：
  2.08
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  7

制备方法与用途

5′-O-TBDMS-dA 是一种修饰核苷，可用于合成 DNA 或 RNA。

反应信息

• 作为反应物：
  描述：

  5'-O-(tert-butyldimethylsilyl)-2'-deoxyadenosine 在 咪唑 、 potassium fluoride 、 偶氮二异丁腈 、 三丁基氯化锡 、 四丁基氟化铵 、 碘 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 水 、 甲苯 、 乙腈 为溶剂， 反应 43.5h， 生成 9-(3'-cyano-2',3'-dideoxy-β-D-erythro-pentofuranosyl)adenine
  参考文献：
  名称：

  Synthesis of 3'-cyano-2',3'-dideoxyadenosine and 2',3'-dideoxy-3'-formyladenosine

  摘要：

  DOI：

  10.1021/jo00274a063
• 作为产物：
  描述：

  (2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-chlorooxolan-3-ol 在 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 甲苯 为溶剂， 反应 2.5h， 以90%的产率得到5'-O-(tert-butyldimethylsilyl)-2'-deoxyadenosine
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/ja962117m

文献信息

• Selective Generation of Free Radicals from Epoxides Using a Transition-Metal Radical. A Powerful New Tool for Organic Synthesis
  作者：T. V. RajanBabu、William A. Nugent

  DOI：10.1021/ja00082a021

  日期：1994.2

  halogens provides a route to functionalized cyclopentanes and other useful products. The radical initially formed from an epoxide can also be trapped by H-atom donors such as 1,4- cyclohexadiene or tert-butyl thiol, resulting in an overall reduction of the epoxide. In the absence of a H-atom donor or an olefin, this radical is trapped by Ti(", resulting in a fl-oxido-Ti organometallic species which undergoes

  双（环戊二烯基）氯化钛 (III) 通过初始 C-0 均裂与环氧化物反应。开口的区域化学由自由基的相对稳定性决定。根据反应伙伴的不同，这些自由基会发生分子内（己-5-烯基环化）或分子间加成到烯烃的过程。生成的自由基被第二当量的 Ti(II1) 有效清除，得到相应的 Ti(1V) 衍生物。用亲电试剂（如 H+ 或卤素）处理该中间体提供了获得官能化环戊烷和其他有用产品的途径。最初由环氧化物形成的自由基也可以被 H 原子供体如 1,4- 环己二烯或叔丁基硫醇捕获，导致环氧化物的整体还原。在没有氢原子供体或烯烃的情况下，环氧化物作为有机合成的构件的相当大的效用反映了它们的现成可用性和它们进行具有可预测立体化学的选择性亲核取代反应(eq la)的能力。相比之下，两 环氧化物作为有机合成的构件的相当大的效用反映了它们的现成可用性和它们进行具有可预测立体化学的选择性亲核取代反应(eq la)的能力。相比之下，两
• [EN] NOVEL PHOSPHOROUS (V)-BASED REAGENTS, PROCESSES FOR THE PREPARATION THEREOF, AND THEIR USE IN MAKING STEREO-DEFINED ORGANOPHOSHOROUS (V) COMPOUNDS<br/>[FR] NOUVEAUX RÉACTIFS À BASE DE PHOSPHORE (V), LEURS PROCÉDÉS DE PRÉPARATION ET LEUR UTILISATION DANS LA FABRICATION DE COMPOSÉS ORGANOPHOSHOREUX (V) STÉRÉODÉFINIS
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2019200273A1

  公开（公告）日：2019-10-17

  The present invention relates to novel phosphorous (V) (P(V)) reagents, methods for preparing thereof, and methods for preparing organophosphorous (V) compounds by using the novel reagents.

  本发明涉及新型磷（V）（P(V)）试剂，其制备方法以及利用这种新型试剂制备有机磷（V）化合物的方法。
• Novel Synthetic Approach to Multibenzoylated Nucleosides
  作者：Xue‐Feng Zhu、A. Ian Scott

  DOI：10.1080/00397910801916280

  日期：2008.4

  Abstract An improved and highly efficient synthetic approach to multibenzoylated nucleosides bearing free 5′‐hydroxyl groups is described here. By employing t-butyldimethylsilyl (TBDMS) rather than the more commonly used dimethoxytrityl (DMTr) as a temporary 5′‐OH protecting group of the starting nucleoside, this methodology provides the expected products in nearly quantitative yields, thereby substantially

  摘要 这里描述了一种改进的、高效的带有游离 5'-羟基的多苯甲酰化核苷的合成方法。通过使用叔丁基二甲基甲硅烷基 (TBDMS) 而不是更常用的二甲氧基三苯甲基 (DMTr) 作为起始核苷的临时 5'-OH 保护基团，该方法以接近定量的产率提供了预期的产品，从而大大降低了成本和工作量的合成。
• Highly selective O-phosphitylation of amino alcohols using PIIIreagents containing 4-nitro and 2,4-dinitro aryloxy leaving groups
  作者：Wojciech Dabkowski、Alfred Ozarek、Izabela Tworowska

  DOI：10.1039/b509150k

  日期：——

  A method for direct highly O-selective phosphitylation of amino alcohols by reagents containing a 4-nitrophenoxy or 2,4 dinitrophenoxy leaving group has been developed. This method provides mild reaction conditions to access O-phosphitylated amino alcohols. The flexibility of the synthesis is exemplified by the models of simple amino alcohols and of nucleosides containing unprotected NH2 groups.

  开发了一种方法，通过含有4-硝基苯氧基或2,4-二硝基苯氧基离去基团的试剂，实现氨基醇的高度O-选择性膦酸化。这种方法提供了温和的反应条件，用于制备O-膦酸化氨基醇。合成方法的灵活性通过简单氨基醇和含有未保护NH2基团的核苷模型得以展示。
• Stereoselective synthesis of dinucleoside phosphate aryl esters by using new condensing reagents, arenesulfonyl 5-(pyridin-2-yl)-tetrazole
  作者：Eiko Ohtsuka、Masahiko Shiraishi、Morio Ikehara

  DOI：10.1016/s0040-4020(01)96777-8

  日期：1985.1

  Deoxyadenylyl-(3'-5')-phosphoro-o-chlorophenyl deoxyadenosine having the Sp configuration was synthesised stereoselectively by condensing N,5'-bis-dimethoxytrityldeoxyadenosine 3'-(o-chlorophenyl) phosphate with N,3'-bis-dimethoxytrityldeoxyadenosine using 1-2,4,6-triisopropylbenzene-5-(pyridin-2-yl) tetrazole as the activating reagent followed by dedimethoxytritylation. The absolute configuration of

  通过将N，5′-双-二甲氧基三苯甲基脱氧腺苷3′-（邻氯苯基）磷酸酯与N，3′-双-缩合缩合，立体选择性地合成具有Sp构型的脱氧腺苷基-（3′-5′）-磷酸-邻氯苯基脱氧腺苷。使用1-2,4,6-三异丙基苯-5-（吡啶-2-基）四唑作为活化剂的二甲氧基三苯甲基脱氧腺苷，然后进行二甲氧基三苯甲基化。该非对映异构体的绝对构型是通过光谱比较两个相应的非对映异构体而确定的，这两个非对映异构体是使用常规的缩合试剂制备的，并通过硅胶色谱法进行分离。仅当通过立体选择性合成获得的产物具有Sp构型时，才能解释它们在质子磁共振中的核Overhauser效应和这两种非对映异构体的圆二色性。