(1'S,2'R,3'S)-1-[2,3-dihydroxy-4-hydroxy methyl-4-cyclopenten-1-yl]-thymine

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: (1'S,2'R,3'S)-1-[2,3-dihydroxy-4-hydroxy methyl-4-cyclopenten-1-yl]-thymine
• 英文别名: 1-[(1S,4S,5R)-4,5-dihydroxy-3-(hydroxymethyl)cyclopent-2-en-1-yl]-5-methyl-pyrimidine-2,4-dione；1-[(1S,4S,5R)-4,5-dihydroxy-3-(hydroxymethyl)cyclopent-2-en-1-yl]-5-methylpyrimidine-2,4-dione
• 化学式: C₁₁H₁₄N₂O₅
• 分子量: 254.243
• InChiKey: ZKQQLROLWCFJDR-XHNCKOQMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  110
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (+/-)-2,2-dimethyl-3αβ,6αβ-dihydro-4H-cyclopenta-1,3-dioxol-4-one 在 吡啶 、 sodium tetrahydroborate 、 cerium(III) chloride 、 氨 、 双氧水 、 三苯基膦 、 三氟乙酸 、 lithium diisopropyl amide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 环己烷 为溶剂， 反应 37.5h， 生成 (1'S,2'R,3'S)-1-[2,3-dihydroxy-4-hydroxy methyl-4-cyclopenten-1-yl]-thymine
  参考文献：
  名称：

  Enantiomeric Synthesis of d- and l-Cyclopentenyl Nucleosides and Their Antiviral Activity Against HIV and West Nile Virus

  摘要：

  Enantiomeric synthesis Of D- and L-cyclopentenyl nucleosides and their antiviral activity against HIV and West Nile virus are described. The key intermediate (-)- and (+)-cyclopentenyl alcohols (7 and 15) were prepared from D-gamma -ribonolactone and D-ribose, respectively. Coupling of 7 with appropriately blocked purine and pyrimidine bases via the Mitsunobu reaction followed by deprotection afforded the target L-(+)-cyclopentenyl nucleosides (24-28, 31, 33, and 36). D-(-)Cyclopentenyl nucleosides (1, 40, 43, and 52-56) were also prepared by a similar procedure for L-isomers from 15. The synthesized compounds were evaluated for their antiviral activity against two RNA viruses: HIV and West Nile virus. Among the synthesized D-(-)-nucleosides, adenine (1, neplanocin A), cytosine (55, CPE-C), and 5-fluorocytosine (56) analogues exhibited moderate to potent anti-HIV activity (EC50 0.1, 0.06, and 5.34 muM, respectively) with significant cytotoxicity in PBM, Vero, and CEM cells. Also, cytosine (55) and 5-fluorocytosine (56) analogues exhibited the most potent anti-West Nile virus activity (EC50 0.2-3.0 and 15-20 muM, respectively). Among L-(+)-nucleosides, only the cytosine (27) analogue exhibited weak anti-HIV activity (EC50 58.9 muM).

  DOI：

  10.1021/jm010256v

文献信息

• Synthesis of l-cyclopentenyl nucleosides using ring-closing metathesis and palladium-mediated allylic alkylation methodologies
  作者：Luigi A. Agrofoglio、Franck Amblard、Steven P. Nolan、Steve Charamon、Isabelle Gillaizeau、Thomas A. Zevaco、Pierre Guenot

  DOI：10.1016/j.tet.2004.07.009

  日期：2004.9

  synthesis of l-cyclopentenyl nucleosides is described. The key intermediate (+)-cyclopentenyl alcohol (8) was prepared from methyl-α-d-galactopyranoside 1 using a ring closing metathesis reaction. Transformation of the allylic alcohol 8 into the allylic acetate (9) or carbonate (10), allows their coupling with purine and pyrimidine bases under Pd(0)-catalyzed Tsuji–Trost allylic alkylation's to yield 12a–c

  描述了1-环戊烯基核苷的对映体合成。使用闭环易位反应由甲基-α-d-吡喃半乳糖苷1制备关键中间体（+）-环戊烯基醇（8）。将烯丙醇8转化为乙酸烯丙酯（9）或碳酸盐（10），使其在Pd（0）催化的Tsuji-Trost烯丙基烷基化反应下与嘌呤和嘧啶碱偶联，得到12a – c。发现钯催化的反应需要使用AlEt 3。
• Enantiomeric Synthesis of <scp>d</scp>- and <scp>l</scp>-Cyclopentenyl Nucleosides and Their Antiviral Activity Against HIV and West Nile Virus
  作者：Gyu Y. Song、Vincent Paul、Hyunah Choo、John Morrey、Robert W. Sidwell、Raymond F. Schinazi、Chung K. Chu

  DOI：10.1021/jm010256v

  日期：2001.11.1

  Enantiomeric synthesis Of D- and L-cyclopentenyl nucleosides and their antiviral activity against HIV and West Nile virus are described. The key intermediate (-)- and (+)-cyclopentenyl alcohols (7 and 15) were prepared from D-gamma -ribonolactone and D-ribose, respectively. Coupling of 7 with appropriately blocked purine and pyrimidine bases via the Mitsunobu reaction followed by deprotection afforded the target L-(+)-cyclopentenyl nucleosides (24-28, 31, 33, and 36). D-(-)Cyclopentenyl nucleosides (1, 40, 43, and 52-56) were also prepared by a similar procedure for L-isomers from 15. The synthesized compounds were evaluated for their antiviral activity against two RNA viruses: HIV and West Nile virus. Among the synthesized D-(-)-nucleosides, adenine (1, neplanocin A), cytosine (55, CPE-C), and 5-fluorocytosine (56) analogues exhibited moderate to potent anti-HIV activity (EC50 0.1, 0.06, and 5.34 muM, respectively) with significant cytotoxicity in PBM, Vero, and CEM cells. Also, cytosine (55) and 5-fluorocytosine (56) analogues exhibited the most potent anti-West Nile virus activity (EC50 0.2-3.0 and 15-20 muM, respectively). Among L-(+)-nucleosides, only the cytosine (27) analogue exhibited weak anti-HIV activity (EC50 58.9 muM).