丙酰胺,2-甲基-N-[2-[(三甲基甲硅烷基)氧代]-4-嘧啶基]- | 138866-74-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 丙酰胺,2-甲基-N-[2-[(三甲基甲硅烷基)氧代]-4-嘧啶基]-
• 英文名称: 2-O-trimethylsilyl-N⁴-isobutyrylcytosine
• 英文别名: Propanamide, 2-methyl-N-[2-[(trimethylsilyl)oxy]-4-pyrimidinyl]-；2-methyl-N-(2-trimethylsilyloxypyrimidin-4-yl)propanamide
• CAS: 138866-74-7
• 化学式: C₁₁H₁₉N₃O₂Si
• 分子量: 253.376
• InChiKey: YDFJBLSQKCSORE-UHFFFAOYSA-N

物化性质

• 密度：
  1.077±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.28
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  64.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  丙酰胺,2-甲基-N-[2-[(三甲基甲硅烷基)氧代]-4-嘧啶基]- 在 三氟甲磺酸三甲基硅酯 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 3.5h， 生成 1-(3-(2-methoxycarbonylethyl)-2,3-dideoxy-β-D-erythro-pentofuranosyl)-N⁴-isobutyrylcytosine
  参考文献：
  名称：

  3-(2-氰乙基)-和3-(2-甲氧羰基乙基)-2,3-二脱氧-α-D-赤型戊呋喃糖苷的自由基合成及其在合成潜在抗病毒核苷中的应用

  摘要：

  在三丁基氢化锡和自由基引发剂 (AIBN) 存在下，不同的碳水化合物离析物 2、5 和 7 与丙烯腈发生自由基反应，得到甲基 3-(2-氰乙基)-2,3-二脱氧戊呋喃糖苷 3a 和 6。 2与丙烯酸甲酯反应得到3-(2-甲氧基羰基乙基>-2,3-二脱氧戊呋喃糖3b。3a与甲硅烷基化尿嘧啶核苷偶联得到β-和α-核苷8和9的异头混合物，脱保护得到10和11，分别。3b 与甲硅烷基化 N4-异丁酰胞嘧啶的类似反应得到 12 和 13，它们被脱保护，分别得到最终的核苷 16 和 17。化合物 10a、11、14-17 都没有显示出显着的抗 HIV 活性。

  DOI：

  10.1002/ardp.2503241203
• 作为产物：
  描述：

  N⁴-isobutyrylcytosine 、 六甲基二硅氮烷 在 ammonium sulfate 作用下， 反应 5.0h， 生成 丙酰胺,2-甲基-N-[2-[(三甲基甲硅烷基)氧代]-4-嘧啶基]-
  参考文献：
  名称：

  Motawia, Mohammed S.; Pedersen, Erik B., Liebigs Annalen der Chemie, 1990, # 6, p. 599 - 602

  摘要：

  DOI：

文献信息

• Stereocontrolled Syntheses of Deoxyribonucleosides via Photoinduced Electron-Transfer Deoxygenation of Benzoyl-Protected Ribo- and Arabinonucleosides
  作者：Zhiwei Wang、Daniel R. Prudhomme、Jason R. Buck、Minnie Park、Carmelo J. Rizzo

  DOI：10.1021/jo0003652

  日期：2000.9.1

  arabinose, and xylose glycosylation precursors were synthesized bearing C2-esters capable of directing Vorbrüggen glycosylation. The key step is the regioselective deoxygenation of the desired hydroxyl group as either the benzoyl- or 3-(trifluoromethyl)benzoyl derivative. This deoxygenation is accomplished via a photoinduced electron-transfer (PET) mechanism using carbazole derivatives as the photosensitizer

  描述了β2'-脱氧-，α2'-脱氧-，β3'-脱氧-和β2'，3'-脱氧核糖核苷的立体控制的从头合成。合成了具有战略指导意义的受保护的核糖，阿拉伯糖和木糖糖基化前体，它们带有能够指导Vorbrüggen糖基化的C2-酯。关键步骤是所需羟基作为苯甲酰基-或3-（三氟甲基）苯甲酰基衍生物的区域选择性脱氧。该脱氧是通过使用咔唑衍生物作为光敏剂的光诱导电子转移（PET）机制完成的。所需脱氧核苷的合成通常从一个容易获得的常见前体分三步进行。
• Synthesis of 3′-Alkylthio-2′,3′-dideoxy Nucleosides with Potential Anti-HIV Activity from 2-Deoxy-D-ribose, Using a Phosphorus Pentoxide Reagent
  作者：Kim L. Dueholm、Mohammed S. Motawia、Erik B. Pedersen、Claus Nielsen、Inge Lundt

  DOI：10.1002/ardp.19923250914

  日期：——

  in coupling at C‐3 to give the anomeric mixtures of the corresponding pentopyranoses 2 and pentofuranoses 3, After acetylation with acetic anhydride in dry pyridine of these 3‐alkylthio pentofuranoses, coupling with the nucleobases uracil, thymine, and cytosine in accordance with the Friedel‐Crafts catalyzed silyl Hilbert‐Johnson method yielded the acetylated D‐erythro nucleosides 7 as anomeric mixtures

  使用 P4O10 / H2O / Bu3N 试剂在氯仿中使 2-脱氧 - D-核糖 (1) 与硫醇直接缩合，导致在 C-3 处偶联，得到相应吡喃戊糖 2 和呋喃戊糖 3 的异头混合物，用乙酸乙酰化后这些 3-烷硫基戊呋喃糖的无水吡啶中的酸酐，根据 Friedel-Crafts 催化的甲硅烷基 Hilbert-Johnson 方法与核碱基尿嘧啶、胸腺嘧啶和胞嘧啶偶联，仅通过分离异构体混合物产生乙酰化 D-赤型核苷 7在用氨去保护之前或之后进行色谱分析。核苷 8a-e 没有任何针对 HSV-1 和 HIV-1 的活性。
• Synthesis of 2′,3′-Dideoxy-D-<i>erythro</i>-hexofuranosyl Nucleosides and 3′-Azido-2′, 3′-dideoxy-D-<i>arabino</i>-hexofuranosyl Nucleosides From Tri-<i>O</i>-acetyl-D-glucal via an α,β-Unsaturated Hexose Aldehyde
  作者：Jesper Lau、Jesper Wengel、Erik B. Pedersen、Bent Faber Vestergaard

  DOI：10.1055/s-1991-28417

  日期：——

  α,β-Unsaturated aldehyde 2 prepared from tri-O-acetyl-D-glucal was acetalated and benzoylated to give α,β-unsaturated acetal 6. Hydrogenation of the double bond followed by methanolysis resulted in methyl 2,3-dideoxyfuranosyl glycoside 8 which was used for nucleoside coupling with silylated N 6-isobutyrylcytosine and silylated thymine. Protected 3-azido-2,3-dideoxy-arabino-furanose 26 was prepared by 1,4-addition of hydrazoic acid to disilylated α,β-unsaturated aldehyde 24 followed by acetylation. Compound 26 was used for the preparation of 3′-azido-2′,3′-dideoxy-D-arabino-hexofuranosyl nucleosides 28 and 29.

  由三-O-乙酰基-D-葡萄糖制备的α,β-不饱和醛2经缩醛化和苯甲酰化得到α,β-不饱和缩醛6。双键氢化，随后甲醇解产生甲基2,3-二脱氧呋喃糖基糖苷8，其用于与甲硅烷基化的N 6-异丁酰胞嘧啶和甲硅烷基化的胸腺嘧啶进行核苷偶联。 受保护的3-叠氮基-2,3-二脱氧-阿拉伯-呋喃糖26 是通过将叠氮酸1,4-加成到二甲硅烷基化的α,β-不饱和醛24 上然后乙酰化来制备的。化合物26用于制备3'-叠氮基-2',3'-二脱氧-D-阿拉伯-呋喃己糖核苷28和29。
• Convergent synthesis of 2′,3′-dideoxy-3′-methylthio and 2′,3′-dideoxy-3′-mercapto nucleosides and their disulfide analogues — Potential anti-HIV agents
  作者：Kim L. Dueholm、Youssef L. Aly、Per T. Jørgensen、Ahmed A. El-Barbary、Erik B. Pedersen、Claus Nielsen

  DOI：10.1007/bf00808508

  日期：1993.1

  The iodide 4(alpha) or 7 synthesized in three steps from 2-deoxy-D-ribose 1, has been subjected to a number of nucleophilic substitution reactions producing the 3-benzoylthio-, 3-methylthio- and the 3-thiocyanato-2,3-dideoxy-D-erythro-pentofuranosides 8,13 and 15, respectively, in addition to the disulfide 17 of their 3-mercapto analogue. Subjecting the thiobenzoate 8 to the Friedel-Crafts catalyzed silyl Hilbert Johnson reaction in conjunction with the silylated nucleobases of uracil, thymine and N4-isobutyrylcytosine 9a-c resulted in the isolation of the 2',3'-dideoxy-3'-mercapto nucleosides 11 and their disulfides 12 subsequent to deprotection. The 2,3-dideoxy-3-methylthio-pentofuranoside 13 afforded both anomers of the 2',3'-dideoxy-3'-methylthio nucleosides 19 and 20 under similar conditions. The first known example of a coupling directly on a 2,3-didehydro-2,3-dideoxyfuranose is presented. 2',3'-Dideoxy-3'-mercaptocytidine showed protection against HIV-1 in MT-4 cells with ED50 = 20 muM.
• 5'-Azido and 5'-Fluoro alpha-Nucleosides as Analogues of AZT and FLT.
  作者：Lone Schmidt、Erik B. Pedersen、Claus Nielsen、Chavdar B. Ivanov、Ralitza Atanasova、Anna Napoli、Giovanni Sindona、Dagfinn W. Aksnes、George W. Francis

  DOI：10.3891/acta.chem.scand.48-0215

  日期：——

  5-Azido-2,5-dideoxy-beta-D-erythro-pentofuranosyl nucleosides 10 and their corresponding alpha-anomers 11 have been synthesized by condensation of methyl 3-O-acetyl-5-azido-2,5-dideoxy-beta-D-erythro-pentofuranoside (7) with silylated nucleobases followed by deprotection with methanolic ammonia. Reaction of silylated thymine (19) with methyl 2,3-di-O-benzoyl-5-deoxy-5-fluoro-D-arabino-pentofuranoside (15) and methyl 5-azido-2,3-di-O-benzoyl-5-deoxy-alpha-D-arabino-pentofuranoside (17alpha) afforded a mixture of the alpha-nucleosides 20 and the acyclo nucleosides 5-fluoro- and 5-azido-2,3-O-dibenzoyl-5-deoxy-1-O-methyl-1-(thymin-1-yl)-D-arabinitol (22). Compounds 20 and 22 were deprotected with methanolic ammonia to give the acyclic nucleosides 21 and 23, respectively. The new nucleosides were inactive against HSV-1 and HIV-1.