(4S)-O-(tert-butyldimethylsilyl)-(2R)-(thymin-1-yl)thian-5-one | 1017604-45-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (4S)-O-(tert-butyldimethylsilyl)-(2R)-(thymin-1-yl)thian-5-one
• 英文别名: 1-[(2R,4S)-4-[tert-butyl(dimethyl)silyl]oxy-5-oxothian-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 1017604-45-3
• 化学式: C₁₆H₂₆N₂O₄SSi
• 分子量: 370.545
• InChiKey: KJHYTOMTIZLCGG-QWHCGFSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.44
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-[3-O-(t-butyldimethylsilyl)-2,5-dideoxy-β-D-glycero-4-eno-4-thiofuranosyl]thymine 、 lead(IV) tetraacetate 以 二氯甲烷 为溶剂， 以58%的产率得到(4S)-O-(tert-butyldimethylsilyl)-(2R)-(thymin-1-yl)thian-5-one
  参考文献：
  名称：

  Synthesis and Anti-HIV Activity of 4′-Substituted 4′-Thiothymidines: A New Entry Based on Nucleophilic Substitution of the 4′-Acetoxy Group

  摘要：

  Diacetoxylation of 1-(2,5-dideoxy-beta-L-glycero-pent-4-eno-4-thiofuranosyl)thymine (13) with Pb(OAc)(4) allowed introduction of an acetoxy leaving group to the 4 '-position. Nucleophilic substitution of the resulting 4 '-acetoxy derivative (14) with silicon reagents enabled us to prepare the 4 '-phenylthio (17a), 4 '-azido (18a), 4 '-methoxy (20a), and 4 '-allyl (21a) analogues of 4 '-thiothymidine. 4 '-Cyano (25a) and 4 '-ethynyl (31) nucleosides were also synthesized from 3 ',5 '-bis-O-TBDMS derivative (24). Among novel 4 '-substituted 4 '-thiothymidines, the 4 '-azido (33), 4 '-cyano (36), and 4 '-ethynyl (37) derivatives were found to show potent inhibitory activity against HIV-1 and HIV-2. It is noteworthy that 36 and 37 were also inhibitory against replication of HIV variant resistant to 3TC (HIV-1(M184V)), being as potent as against HIV-1(IIIB).

  DOI：

  10.1021/jm070824s

文献信息

• Synthesis and Anti-HIV Activity of 4′-Substituted 4′-Thiothymidines: A New Entry Based on Nucleophilic Substitution of the 4′-Acetoxy Group
  作者：Kazuhiro Haraguchi、Hisashi Shimada、Hiromichi Tanaka、Takayuki Hamasaki、Masanori Baba、Elizabeth A. Gullen、Ginger E. Dutschman、Yung-Chi Cheng

  DOI：10.1021/jm070824s

  日期：2008.3.1

  Diacetoxylation of 1-(2,5-dideoxy-beta-L-glycero-pent-4-eno-4-thiofuranosyl)thymine (13) with Pb(OAc)(4) allowed introduction of an acetoxy leaving group to the 4 '-position. Nucleophilic substitution of the resulting 4 '-acetoxy derivative (14) with silicon reagents enabled us to prepare the 4 '-phenylthio (17a), 4 '-azido (18a), 4 '-methoxy (20a), and 4 '-allyl (21a) analogues of 4 '-thiothymidine. 4 '-Cyano (25a) and 4 '-ethynyl (31) nucleosides were also synthesized from 3 ',5 '-bis-O-TBDMS derivative (24). Among novel 4 '-substituted 4 '-thiothymidines, the 4 '-azido (33), 4 '-cyano (36), and 4 '-ethynyl (37) derivatives were found to show potent inhibitory activity against HIV-1 and HIV-2. It is noteworthy that 36 and 37 were also inhibitory against replication of HIV variant resistant to 3TC (HIV-1(M184V)), being as potent as against HIV-1(IIIB).