1-[5-O-benzoyl-3-O-(tert-butyldimethylsilyl)-4-chloro-2-deoxy-β-D-threo-pentofuranosyl]thymine | 897037-31-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-[5-O-benzoyl-3-O-(tert-butyldimethylsilyl)-4-chloro-2-deoxy-β-D-threo-pentofuranosyl]thymine
• 英文别名: [(2S,3R,5R)-3-[tert-butyl(dimethyl)silyl]oxy-2-chloro-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl benzoate
• CAS: 897037-31-9
• 化学式: C₂₃H₃₁ClN₂O₆Si
• 分子量: 495.047
• InChiKey: RJFRULBWGNKCNL-PMAPCBKXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.95
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  94.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-[5-O-benzoyl-3-O-(tert-butyldimethylsilyl)-4-chloro-2-deoxy-β-D-threo-pentofuranosyl]thymine 在 吡啶 、 敌草腈 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 7.5h， 生成 festinavir
  参考文献：
  名称：

  Nucleophilic Substitution at the 4‘-Position of Nucleosides: New Access to a Promising Anti-HIV Agent 2‘,3‘-Didehydro-3‘-deoxy-4‘-ethynylthymidine

  摘要：

  For the synthesis of 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine (8: 4'-Ed4T), a recently reported promising anti-HIV agent, a new approach was developed. Since treatment of 1-(2,5-dideoxy-beta-L-glyceropent4- enofuranosyl) thymine with Pb(OBz) 4 allowed the introduction of the 4'-benzoyloxy leaving group, nucleophilic substitution at the 4'-position became feasible for the first time. Thus, reaction between the 4'-benzoyloxy derivative (14) and Me3SiC CAl(Et) Cl as a nucleophile led to the isolation of the desired 4'-"down"-ethynyl derivative (18) stereoselectively in 62% yield. As an application of this approach, other 4'-substituted nucleosides, such as the 4'-allyl (24a) and 4'-cyano (26a) derivatives, were synthesized using organosilicon reagents. In these instances, pretreatment of 14 with MeAlCl2 was necessary.

  DOI：

  10.1021/jo060194m
• 作为产物：
  描述：

  [(3R,5R)-2-benzoyloxy-3-[tert-butyl(dimethyl)silyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl benzoate 在 甲基二氯化铝 作用下， 以 二氯甲烷 为溶剂， 以53%的产率得到1-[5-O-benzoyl-3-O-(tert-butyldimethylsilyl)-4-chloro-2-deoxy-β-D-threo-pentofuranosyl]thymine
  参考文献：
  名称：

  An Alternative Synthetic Method for 4′-C-Ethynylstavudine by Means of Nucleophilic Substitution of 4′-Benzoyloxythymine Nucleoside

  摘要：

  For the synthesis of 2,3'-didehydro-3'-deoxy-4'-C-ethynylthymidine (8: 4'-Ed4T), a recently reported promising anti-HIV agent, a new approach was developed. Since treatment of 1-(2,5-dideoxy-beta-L-glycero-pent-4-enofuranosyl)thymine with Pb(OBz)(4) allowed the introduction of a 4'-benzoyloxy leaving group, nucleophilic substitution at the 4'-position became feasible, for the first time. Thus, reaction between the 4'-benzoyloxy derivative (H) and Me3SiC CAl(Et)Cl as a nucleophile led to the isolation of the desired 4'-"down"-ethynyl derivative (15) stereoselectively in 62 % yield.

  DOI：

  10.1080/15257770701503969

文献信息

• Nucleophilic Substitution at the 4‘-Position of Nucleosides: New Access to a Promising Anti-HIV Agent 2‘,3‘-Didehydro-3‘-deoxy-4‘-ethynylthymidine
  作者：Kazuhiro Haraguchi、Masanori Sumino、Hiromichi Tanaka

  DOI：10.1021/jo060194m

  日期：2006.6.1

  For the synthesis of 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine (8: 4'-Ed4T), a recently reported promising anti-HIV agent, a new approach was developed. Since treatment of 1-(2,5-dideoxy-beta-L-glyceropent4- enofuranosyl) thymine with Pb(OBz) 4 allowed the introduction of the 4'-benzoyloxy leaving group, nucleophilic substitution at the 4'-position became feasible for the first time. Thus, reaction between the 4'-benzoyloxy derivative (14) and Me3SiC CAl(Et) Cl as a nucleophile led to the isolation of the desired 4'-"down"-ethynyl derivative (18) stereoselectively in 62% yield. As an application of this approach, other 4'-substituted nucleosides, such as the 4'-allyl (24a) and 4'-cyano (26a) derivatives, were synthesized using organosilicon reagents. In these instances, pretreatment of 14 with MeAlCl2 was necessary.
• An Alternative Synthetic Method for 4′-C-Ethynylstavudine by Means of Nucleophilic Substitution of 4′-Benzoyloxythymine Nucleoside
  作者：Kazuhiro Haraguchi、Masanori Sumino、Hiromichi Tanaka

  DOI：10.1080/15257770701503969

  日期：2007.11.26

  For the synthesis of 2,3'-didehydro-3'-deoxy-4'-C-ethynylthymidine (8: 4'-Ed4T), a recently reported promising anti-HIV agent, a new approach was developed. Since treatment of 1-(2,5-dideoxy-beta-L-glycero-pent-4-enofuranosyl)thymine with Pb(OBz)(4) allowed the introduction of a 4'-benzoyloxy leaving group, nucleophilic substitution at the 4'-position became feasible, for the first time. Thus, reaction between the 4'-benzoyloxy derivative (H) and Me3SiC CAl(Et)Cl as a nucleophile led to the isolation of the desired 4'-"down"-ethynyl derivative (15) stereoselectively in 62 % yield.