(2S,4S)-(+)-4-tert-butyldiphenylsilyloxymethyl-2-fluoro-γ-butyrolactone | 476209-84-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (2S,4S)-(+)-4-tert-butyldiphenylsilyloxymethyl-2-fluoro-γ-butyrolactone
• 英文别名: (3S,5S)-3-fluoro-5-(tert-butyldiphenylsiloxy)pentan-4-olide；(3S,5S)-5-[[tert-butyl(diphenyl)silyl]oxymethyl]-3-fluorooxolan-2-one
• CAS: 476209-84-4
• 化学式: C₂₁H₂₅FO₃Si
• 分子量: 372.512
• InChiKey: GYUNRABPNCIDMG-LPHOPBHVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.22
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,4S)-(+)-4-tert-butyldiphenylsilyloxymethyl-2-fluoro-γ-butyrolactone 在 bismuth(III) bromide 、 三甲基溴硅烷 、 二异丁基氢化铝 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 72.0h， 生成 6-chloro-9-(2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl)-9H-purine
  参考文献：
  名称：

  A concise synthesis of anti-viral agent F-ddA, starting from (S)-dihydro-5-(hydroxymethyl)-2(3H)-furanone

  摘要：

  Anti-HIV agent beta-F-ddA (1) has been synthesized starting from readily available non-sugar, (S)-(+)-Dihydro-5-(hydroxymethyl)-2-(3H)-furanone (4). A highly sa n-stereoselective fluorination of the hydroxy lactone 2 generates the key intermediate fluorolactone 5 in a short and concise synthetic sequence. Reduction of 5 followed by bromination generates the aglycon which is glycosylated to generate F-ddA by amination and deprotection. Steric bulk of the 5-protecting group has minimal effect on the steric course of glycosylation. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(02)02532-7
• 作为产物：
  描述：

  5-(羟基甲基)二氢-2(3H)-呋喃酮 在 二乙胺基三氟化硫 、 MeOPH Jacobsen's catalyst 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (2S,4S)-(+)-4-tert-butyldiphenylsilyloxymethyl-2-fluoro-γ-butyrolactone
  参考文献：
  名称：

  A concise synthesis of anti-viral agent F-ddA, starting from (S)-dihydro-5-(hydroxymethyl)-2(3H)-furanone

  摘要：

  Anti-HIV agent beta-F-ddA (1) has been synthesized starting from readily available non-sugar, (S)-(+)-Dihydro-5-(hydroxymethyl)-2-(3H)-furanone (4). A highly sa n-stereoselective fluorination of the hydroxy lactone 2 generates the key intermediate fluorolactone 5 in a short and concise synthetic sequence. Reduction of 5 followed by bromination generates the aglycon which is glycosylated to generate F-ddA by amination and deprotection. Steric bulk of the 5-protecting group has minimal effect on the steric course of glycosylation. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(02)02532-7

文献信息

• Stereoselective Synthesis and Antiviral Activity of <scp>d</scp>-2‘,3‘-Didehydro-2‘,3‘-dideoxy-2‘-fluoro-4‘-thionucleosides
  作者：Youhoon Chong、Hyunah Choo、Yongseok Choi、Judy Mathew、Raymond F. Schinazi、Chung K. Chu

  DOI：10.1021/jm020246+

  日期：2002.10.1

  As 2',3'-didehydro-2',3'-dideoxy-2'-fluoronucleosides have exhibited interesting antiviral effects against HIV-1 as well as HBV, it is of interest to synthesize the isosterically substituted 4'-thionucleosides in which 4'-oxygen is replaced by a sulfur atom. To study structure-activity relationships, various pyrimidine and purine nucleosides were synthesized from the key intermediate (2R,4S)-1-O-a

  由于2'，3'-didehydro-2'，3'-dideoxy-2'-氟核苷对HIV-1和HBV表现出令人感兴趣的抗病毒作用，因此，合成等位取代的4'-硫代核苷令人感兴趣。 4'-氧被硫原子取代。为了研究结构活性关系，从关键中间体（2R，4S）-1-O-乙酰-5-O-（叔丁基二苯基甲硅烷基）-2,3-二脱氧-2-氟-合成了各种嘧啶和嘌呤核苷。由2，3-O-异亚丙基-D-甘油醛1以13个步骤制备2-苯基硒基-4-硫代-β-D-呋喃呋喃糖苷8。在人外周血单核（PBM）细胞中评估了合成化合物对HIV-1的抗病毒活性，其中包括胞苷17、5-氟胞苷18，腺苷24，和2-氟腺苷32显示中等至有效的抗HIV活性（分别为EC（50）1.3、11.6、8.1和1.2 microM）。值得注意的是，2-氟腺苷类似物32显示出抗病毒效力以及高细胞毒性（对于PBM，CEM和Vero，IC（50）分别为1.5、1.1和7
• 2′-Fluoro-4′-thio-2′,3′-unsaturated Nucleosides: Anti-HIV Activity, Resistance Profile, and Molecular Modeling Studies
  作者：Youhoon Chong、Hyunah Choo、Raymond F. Schinazi、Chung K. Chu

  DOI：10.1081/ncn-120021965

  日期：2003.10

  Both D- and L-2'-fluoro-4-thio-2',3'-unsaturated nucleosides were synthesized and their anti-HIV activity against the drug sensitive virus and lamivudine-resistant mutant (M184V) were evaluated. In vitro antiviral evaluation indicated that the L-isomers are more potent than the D-isomers, but unfortunately all were cross-resistant with 3TC. Molecular modeling studies revealed that the unnatural sugar moiety of the L-nucleosides as well as 4'-sulfur atom of the D-isomer has a steric conflict with the bulky side chain of valine 184, resulting in cross-resistance.