9-(3-O-acetyl-2-bromo-2-deoxy-5-O-(2,4,4-trimethyl-5-oxo-1,3-dioxolan-2-yl)-β-D-arabinofuranosyl)adenine | 90144-66-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 9-(3-O-acetyl-2-bromo-2-deoxy-5-O-(2,4,4-trimethyl-5-oxo-1,3-dioxolan-2-yl)-β-D-arabinofuranosyl)adenine
• 英文别名: 5'-[2,5,5-trimethyl-1,3-dioxolane-4-one-2-yl]-2'-bromo-2'-deoxy-3'-O-acetyladenosine；2-[O³-acetyl-1-(6-amino-purin-9-yl)-2-bromo-β-D-1,2-dideoxy-arabinofuranos-5-yl]-2,4,4-trimethyl-[1,3]dioxolan-4-one；[(2R,3R,4S,5R)-5-(6-aminopurin-9-yl)-4-bromo-2-[(2,4,4-trimethyl-5-oxo-1,3-dioxolan-2-yl)oxymethyl]oxolan-3-yl] acetate
• CAS: 90144-66-4
• 化学式: C₁₈H₂₂BrN₅O₇
• 分子量: 500.306
• InChiKey: FXGFTRJVJDNNKL-CKZMXGJVSA-N

物化性质

• 沸点：
  681.7±65.0 °C(Predicted)
• 密度：
  1.80±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  150
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  在 氢溴酸 作用下， 以 乙腈 为溶剂， 生成 9-(3-O-acetyl-2-bromo-2-deoxy-5-O-(2,4,4-trimethyl-5-oxo-1,3-dioxolan-2-yl)-β-D-arabinofuranosyl)adenine 、 9-(2-O-acetyl-3-bromo-3-deoxy-5-O-(2,4,4-trimethyl-5-oxo-1,3-dioxolan-2-yl)-β-D-xylofuranosyl)adenine
  参考文献：
  名称：

  From Adenosine to 3‘-Deoxyadenosine:  Development and Scale Up

  摘要：

  A manufacturing process has been developed suitable for the production of 3'-deoxyadenosine (cordycepin, 3'-dA) in 20% yield from adenosine, The chemistry involves conversion of adenosine to isomeric 2',3'-bromoacetates with isolation of the desired isomer in high purity. Acidic hydrolysis followed by hydrogenolysis afforded product with a purity of greater than or equal to 99%, Unlike routes reported in the literature, intermediates are isolated as solids, thus avoiding the use of chromatography for isomer separation and final product purification.

  DOI：

  10.1021/op000209x

文献信息

• A Convenient Method for the Synthesis of 2′,3′-Didehydro-2′,3′-Dideoxy Nucleosides
  作者：Erwin Dorland、Pawel Serafinowski

  DOI：10.1055/s-1992-26141

  日期：——

  9-(2,3-Dideoxy-β-D-glyceropent-2-enofuranosyl)adenine (2′,3′-didehydro-2′,3′-dideoxyadenosine, 9a), 9-(2,3-dideoxy-β-D-glyceropent-2-enofuranosyl)hypoxanthine (2′,3′-didehydro-2′,3′-dideoxyinosine, 9b) and 4-amino-7-(2,3-dideoxy-β-D-glyceropent-2-enofuranosyl)pyrrolo[2,3-d]pyrimidine (2′,3′-didehydro-2′,3′-dideoxytubercidin, 9c) were prepared via a free radical β-elimination of bromo and phenoxy(thiocarbonyl) leaving groups from appropriate 5′-O-(2-acetoxyisobutyryl)-2′(3′)-phenoxy(thiocarbonyl)-3′(2′)-bromo derivatives 6, 7 of adenosine (1a), inosine (1b) and tubercidin (1c) with tributyltin hydride and subsequent deprotection of the resulting 5′-O-(2-acetoxyisobutyryl)-2′,3′-didehydro-2′,3′-dideoxynucleosides 8a, 8b and 8c, respectively.

  通过自由基β-消除反应，从适当的5′-O-(2-乙酰氧异丁酰基)-2′(3′)-苯氧(硫羰基)-3′(2′)-溴代衍生物6、7中去除溴和苯氧(硫羰基)离去基团，制备了9-(2,3-二脱氧-β-D-甘油戊-2-烯呋喃糖基)腺苷(2′,3′-二脱氢-2′,3′-二脱氧腺苷，9a)、9-(2,3-二脱氧-β-D-甘油戊-2-烯呋喃糖基)次黄嘌呤(2′,3′-二脱氢-2′,3′-二脱氧肌苷，9b)和4-氨基-7-(2,3-二脱氧-β-D-甘油戊-2-烯呋喃糖基)吡咯并[2,3-d]嘧啶(2′,3′-二脱氢-2′,3′-二脱氧结核菌素，9c)。这些化合物分别由腺苷(1a)、肌苷(1b)和结核菌素(1c)与三丁基锡氢化物反应，然后分别对得到的5′-O-(2-乙酰氧异丁酰基)-2′,3′-二脱氢-2′,3′-二脱氧核苷8a、8b和8c进行脱保护。
• Modified nucleosides for the treatment of viral infections and abnormal cellular proliferation
  申请人：Gilead Pharmasset LLC

  公开号：US10100076B2

  公开（公告）日：2018-10-16

  The disclosed invention is a composition for and a method of seating a Flaviviridae (including BVDV and HCV), Orthomyxoviridae (including Influenza A and B) or Paramyxoviridae (including RSV) infection, or conditions related to abnormal cellular proliferation, in a host, including animals, and especially humans, using a nucleoside of general formula (I)-(XXIII) or its pharmaceutically acceptable salt or prodrug. This invention also provides an effective process to quantify the viral load, and in particular BVDV, HCV or West Nile Virus load, in a host, using real-time polymerase chain reaction (“RT-PCR”). Additionally, the invention discloses probe molecules that can fluoresce proportionally to the amount of virus present in a sample.

  所述的发明是关于一种用于在宿主中（包括动物，特别是人类）使用一般式（I）-（XXIII）的核苷或其药用可接受的盐或前药，对Flaviviridae（包括BVDV和HCV）、Orthomyxoviridae（包括流感A和B）或Paramyxoviridae（包括RSV）感染，或与异常细胞增殖相关的疾病进行座位的组合物和方法。该发明还提供了一种有效的过程，用于使用实时聚合酶链反应（“RT-PCR”）在宿主中定量病毒载量，特别是BVDV、HCV或西尼罗河病毒载量。此外，该发明还揭示了可以与样本中存在的病毒量成比例发出荧光的探针分子。
• 一种虫草素的合成方法
  申请人：深圳松乐生物科技有限公司

  公开号：CN104961787B

  公开（公告）日：2020-06-26

  本发明公开了一种虫草素的合成方法，该方法以腺苷为起始原料，和2‑乙酰氧基异丁酰溴(Mattock’s bromide)在以乙腈和/或乙酸乙酯作为反应溶剂，在进行羟基保护的同时进行溴化反应，得到两种产物，即5’‑[2，5，5‑三甲基‑1，3‑二氧环戊烷‑4‑酮‑2‑基]‑3’‑溴‑3’‑脱氧‑2’‑O‑乙酰基腺苷和5’‑[2，5，5‑三甲基‑1，3‑二氧环戊烷‑4‑酮‑2‑基]‑2’‑溴‑2’‑脱氧‑3’‑O‑乙酰基腺苷，然后去保护基团，得到3’‑溴‑3’‑脱氧‑腺苷盐酸盐，再经脱溴反应得到目标物3’‑脱氧腺苷即虫草素。本发明的合成方法操作工艺简单，反应步骤短，反应过程无需纯化处理，得到的产物的纯度和各项指标均优于目前市售的虫草素的产品。
• Preparation of 1-(2,3-dideoxy-.beta.-D-glycero-pent-2-enofuranosyl)thymine (d4T) and 2',3'-dideoxyadenosine (ddA): general methods for the synthesis of 2',3'-olefinic and 2',3'-dideoxy nucleoside analogs active against HIV
  作者：Muzammil M. Mansuri、John E. Starrett、John A. Wos、David R. Tortolani、Paul R. Brodfuehrer、Henry G. Howell、John C. Martin

  DOI：10.1021/jo00281a017

  日期：1989.9
• Nucleic Acid-Related Compounds. 88. Efficient Conversions of Ribonucleosides into Their 2',3'-Anhydro, 2'(and 3')-Deoxy, 2',3'-Didehydro-2',3'-dideoxy, and 2',3'-Dideoxynucleoside Analogs
  作者：Morris J. Robins、John S. Wilson、Danuta Madej、Nicholas H. Low、Fritz Hansske、Stanislaw F. Wnuk

  DOI：10.1021/jo00129a034

  日期：1995.12

  Treatment of purine, pyrimidine, and modified purine (antibiotic) ribonucleosides with 2-acetoxy-2-methylpropanoyl (alpha-acetoxyisobutyryl) bromide in acetonitrile gave mixtures of 2',3'-bromohydrin acetates with different O5' substituents. Significant amounts of 5'-unprotected (hydroxyl) bromo acetates were obtained in some cases, and formation of 2',3'-O-isopropylidene derivatives as minor byproducts was detected for the first time. Acid-catalyzed nucleophilic displacement of chloride by bromide occurred with 2-amino-6-chloropurine riboside, but no substitution of fluoride by bromide was detected with 6-amino-2-fluoropurine riboside. Treatment of the trans bromo acetate mixtures obtained from purine-type nucleosides with Dowex 1 x 2 (OH-) in methanol gave the 2',3'-anhydro (ribo epoxide) compounds. Radical-mediated hydrogenolytic debromination and deprotection gave 2'- and 3'-deoxynucleosides. Treatment of the bromo acetate mixtures with zinc-copper couple or acetic acid-activated zinc effected reductive elimination, and deprotection gave 2',3'-didehydro-2',3'-dideoxy compounds which were hydrogenated to give 2',3'-dideoxynucleosides. A number of these analogues have potent inhibitory activity against AIDS and hepatitis B viruses. New C-13 NMR data for several types of unsaturated-sugar nucleosides are tabulated. These procedures are directly applicable for the preparation of L-didehydro-dideoxy and L-dideoxy nucleoside analogues.