1-(2,3-epoxy-5-O-trityl-β-D-lyxo-pentofuranosyl)thymine | 115913-84-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 1-(2,3-epoxy-5-O-trityl-β-D-lyxo-pentofuranosyl)thymine
• 英文别名: 1-(5'-O-trityl-2',3'-epoxy-β-D-lyxosyl)-5-methyluracil；1-(2,3-anhydro-5-O-trityl-β-D-lyxofuranosyl)thymine；1-(5-O-trityl-2,3-anhydro-β-D-lyxofuranosyl)thymine；1-[2,3-anhydro-5-O-trityl-β-D-lyxofuranosyl]thymine；1-(5-O-trityl-2,3-epoxy-β-D-lyxofuranosyl)thymine；5-methyl-1-[(1S,2R,4R,5S)-4-(trityloxymethyl)-3,6-dioxabicyclo[3.1.0]hexan-2-yl]pyrimidine-2,4-dione
• CAS: 115913-84-3
• 化学式: C₂₉H₂₆N₂O₅
• 分子量: 482.536
• InChiKey: QMSRJJMIGNGSTE-DPRQWMOBSA-N

物化性质

• 熔点：
  174-175 °C
• 密度：
  1.294±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  80.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2,3-epoxy-5-O-trityl-β-D-lyxo-pentofuranosyl)thymine 在 三乙基硅烷 、 Wilkinson's catalyst 、 N,N'-硫羰基二咪唑 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 48.0h， 生成 1-(3'-cyano-2',3'-dideoxy-5'-O-trityl-β-D-threo-pentofuranosyl)thymine
  参考文献：
  名称：

  Synthesis and Anti-HIV Activity of 3'-Cyano-2',3'-dideoxythymidine and 3'-Cyano-2',3'-didehydro-2',3'-dideoxythymidine

  摘要：

  DOI：

  10.3987/com-88-4708
• 作为产物：
  描述：

  5-甲基尿甙 在 吡啶 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 7.0h， 生成 1-(2,3-epoxy-5-O-trityl-β-D-lyxo-pentofuranosyl)thymine
  参考文献：
  名称：

  潜在的抗HIV-1核苷的氟化糖类似物。

  摘要：

  为了获得具有优于AZT，FLT或D4T的治疗指数的药物，合成了抗HIV-1核苷的几种类似物。这些包括2'，3'-dideoxy-2'，3'-difluoro-5-methyluridine（13），其阿拉伯糖类似物19，arab-5--5-甲基胞嘧啶类似物21、3'-脱氧2'，3'-二氢-2'-氟胸苷（25），3'-叠氮基2'，3'-二脱氧基2'-氟-5-甲基尿苷（29），2'-叠氮基3'-氟-2'，3'-双脱氧-5-甲基尿苷（31）和2'3'-二脱氧-2'-氟-5-甲基尿苷（37）。对这些新核苷在体外针对HIV和猫TLV的活性进行了筛选。没有一种化合物显示出明显的活性。有趣的是，活性抗HIV核苷的糖部分有这么小的修饰（即

  DOI：

  10.1021/jm00109a017

文献信息

• Antiviral Activity of Various 1-(2′-Deoxy-β-<scp>d</scp>-lyxofuranosyl), 1-(2′-Fluoro-β-<scp>d</scp>-xylofuranosyl), 1-(3′-Fluoro-β-<scp>d</scp>-arabinofuranosyl), and 2′-Fluoro-2′,3′-didehydro-2′,3′-dideoxyribose Pyrimidine Nucleoside Analogues against Duck Hepatitis B Virus (DHBV) and Human Hepatitis B Virus (HBV) Replication
  作者：Naveen C. Srivastav、Neeraj Shakya、Michelle Mak、Babita Agrawal、D. Lorne Tyrrell、Rakesh Kumar

  DOI：10.1021/jm100803c

  日期：2010.10.14

  3′-fluoroarabinofuranosyl, and 2′-fluoro-2′,3′-didehydro-2′,3′-dideoxyribose pyrimidine nucleoside analogues for antiviral activities against hepatitis B virus. Among the compounds examined, 1-(2-deoxy-β-d-lyxofuranosyl)thymine (23), 1-(2-deoxy-β-d-lyxofuranosyl)-5-trifluoromethyluracil (25), 1-(2-deoxy-2-fluoro-β-d-xylofuranosyl)uracil (38), 1-(2-deoxy-2-fluoro-β-d-xylofuranosyl)thymine (39), 2′,3′-dideoxy-2′,3′-d

  尽管存在成功的疫苗和抗病毒疗法，但乙型肝炎病毒（HBV）的感染仍然是急性和慢性肝病以及高死亡率的全球主要原因。我们合成并评估了几种lyxofuranosyl，2'-fluorooxylofuranosyl，3'-fluoroarabinofuranosyl和2'-fluoro-2'，3'-didehydro-2'，3'-dideoxyribose嘧啶核苷类似物对乙型肝炎病毒的抗病毒活性。在所检查的化合物中，1-（2-脱氧-β - d-呋喃呋喃糖基）胸腺嘧啶（23），1-（2-脱氧-β - d-呋喃呋喃糖基）-5-三氟甲基尿嘧啶（25），1-（2-脱氧-2-氟-β - d-木呋喃糖基）尿嘧啶（38），1-（2-脱氧-2-氟-β- d-二呋喃呋喃糖基）胸腺嘧啶（39），2'，3'-二脱氧-2'，3'-二脱氢-2'-氟胸苷（48）和2'，3'-二脱氧-2'，3'-二脱氢-2在原代鸭肝细胞中发现'
• Synthesis and antiviral activity of 3'-deoxy-3'-C-hydroxymethyl nucleosides
  作者：Mark J. Bamford、Paul L. Coe、Richard T. Walker

  DOI：10.1021/jm00171a025

  日期：1990.9

  allowed high yielding hydrolysis of the 3'-function to give the 3'-deoxy-3'-C-formyl-beta-D-arabino-pentofuranosyl nucleosides 21 and 22. Desilylation afforded the 1-(3-deoxy-3-C-formyl-beta- D-lyxo-pentofuranosyl) 3',5'-O-hemiacetal nucleosides 33 and 34, respectively. Reduction of the formyl group of 21 and 22, followed by desilylation, yielded the 3'-deoxy-3'-C-(hydroxymethyl)-beta-D-arabino- pentofuranosyl)

  已经合成了一系列的3'-支链糖核苷，特别是3'-脱氧-3'-C-羟甲基核苷，并将其评估为抗病毒剂。尿嘧啶和胸腺嘧啶的1-（2,3-环氧-5-O-三苯甲基-β-D-lyxo-五氟呋喃糖基）衍生物12和13分别与5,6-二氢-2-lithio-5-甲基-1,3,5-二噻嗪14分别提供相应的3'-官能化核苷15和16。用叔丁基二苯基甲硅烷基取代三苯甲基可高产率地水解3'-官能团，得到3'-脱氧-3'-C-甲酰基-β-D-阿拉伯糖基-戊呋喃糖基核苷21和22。甲硅烷基化得到1-（ 3-脱氧-3-C-甲酰基-β-D-lyxo-戊呋喃糖基）3'，5'-O-半缩醛核苷33和34。还原21和22的甲酰基，然后进行甲硅烷基化，分别产生3'-脱氧-3'-C-（羟甲基）-β-D-阿拉伯糖基-呋喃呋喃糖基）类似物7和8。将7的尿嘧啶碱基部分转化为5-碘尿嘧啶，然后转化为（E）-5-（2-溴乙烯基）尿嘧啶，以提供B
• Synthesis and Anti‐HIV Activity of 4′‐Cyano‐2′,3′‐didehydro‐3′‐deoxythymidine
  作者：Kazuhiro Haraguchi、Yoshiharu Itoh、Shingo Takeda、Yosuke Honma、Hiromichi Tanaka、Takao Nitanda、Masanori Baba、Ginger E. Dutschman、Yung‐Chi Cheng

  DOI：10.1081/ncn-120030721

  日期：2004.12.31

  new anti-HIV agent 4'-cyano-2',3'-didehydro-3'-deoxythymidine (9) was synthesized by allylic substitution of the 3',4'-unsaturated nucleoside 14, having a leaving group at the 2'-position, with cyanotrimethylsilane in the presence of SnCl4. Evaluation of the anti-HIV activity of 9 showed that this compound is much less potent than the recently reported 2',3'-didehydro-3'-deoxy-4'-(ethynyl)thymidine (1)

  通过对3'，4'-不饱和核苷14进行烯丙基取代，合成了一种新的抗HIV剂4'-cyano-2'，3'-didehydro-3'-脱氧胸苷（9）在氰化三甲基硅烷存在下，在SnCl4存在的情况下在α-位。对9的抗HIV活性的评估表明，该化合物的药效比最近报道的2'，3'-didehydro-3'-deoxy-4'-（ethynyl）thymidine（1）强得多。
• 3′-Bromo Analogues of Pyrimidine Nucleosides as a New Class of Potent Inhibitors of<i>Mycobacterium tuberculosis</i>
  作者：Neeraj Shakya、Naveen C. Srivastav、Nancy Desroches、Babita Agrawal、Dennis Y. Kunimoto、Rakesh Kumar

  DOI：10.1021/jm100165w

  日期：2010.5.27

  Tuberculosis (TB) is a major health problem worldwide. We herein report a new class of pyrimidine nucleosides as potent inhibitors of Mycobacterium tuberculosis (M. tuberculosis). Various 2'- or 3'-halogeno derivatives of pyrimidine nucleosides containing uracil, 5-fluorouracil, and thymine bases were synthesized and evaluated for antimycobacterial activities. Among the compounds tested, 3'-bromo-3'-deoxy-arabinofuranosylthymine (3') was the most effective antituberculosis agent in the in vitro assays against wild-type M. tuberculosis strain (H37Ra) (MIC50 = 1 mu g/mL) as well as drug-resistant (H37Rv) (rifampicin-resistant and isoniazid-resistant) strains of M. tuberculosis (MIC50 = 1-2 mu g/mL). Compound 3' also inhibited intracellular M. tuberculosis in a human monocytic cell line infected with H37Ra, demonstrating higher activity against intramacrophagic mycobacteria (80% reduction at 10 mu g/mL concentration) than extracellular mycobacteria (75% reduction at 10 mu g/mL concentration). In contrast, pyrimidine nucleosides possessing 5-fluorouracil base were weak inhibitors of M. tuberculosis. No cytotoxicity was found up to the highest concentration of compounds tested (CC50 > 100-200 mu g/mL) against a human cell line. Overall, these encouraging results substantiate the potential of this new class of compounds as promising antituberculosis agents.
• Synthesis and anti-HIV activity of different sugar-modified pyrimidine and purine nucleosides
  作者：Piet Herdewijn、Jan Balzarini、Masanori Baba、Rudi Pauwels、Arthur Van Aerschot、Gerard Janssen、Erik De Clercq

  DOI：10.1021/jm00118a033

  日期：1988.10

  A series of base-modified pyrimidine 3'-azido-2',3'-dideoxynucleosides and 3'-substituted purine and pyrimidine 2',3'-dideoxynucleosides have been synthesized and evaluated for their inhibitory activity against human immunodeficiency virus (HIV) replication in MT-4 cells. The following pyrimidine derivatives emerged as the most potent and/or selective inhibitors of HIV-induced cytopathogenicity (in order of decreasing selectivity: 3'-azido-3'-deoxythymidine (AZT), 3'-azido-2',3'-dideoxyuridine (AzddUrd), 3'-azido-2',3'-dideoxy-5-methylcytidine (AzddMeCyd), 3'-fluoro-ddUrd (FddUrd), 3'-fluoro-ddThd (FddThd), the N4-hydroxylated derivative of AzddMeCyd and the N4-methylated derivative of AzddMeCyd. Among the purine 2',3'-dideoxynucleosides, 3'-azido-2',3'-dideoxyguanosine (AzddGuo), 3'-fluoro-ddGuo (FddGuo), and 3'-fluoro-2,6-diaminopurine 2',3'-dideoxynucleoside (FddDAPR) were the most selective inhibitors of HIV replication.