1,4-anhydro-2-deoxy-2-fluoro-3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-4-thio-D-arabinitol | 878384-15-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 硫杂环戊烷
• 英文名称: 1,4-anhydro-2-deoxy-2-fluoro-3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-4-thio-D-arabinitol
• 英文别名: (6aR,9S,9aS)-9-fluoro-2,2,4,4-tetra(propan-2-yl)-6a,8,9,9a-tetrahydro-6H-thieno[3,2-f][1,3,5,2,4]trioxadisilocine
• CAS: 878384-15-7
• 化学式: C₁₇H₃₅FO₃SSi₂
• 分子量: 394.699
• InChiKey: KUOSOAOAEBJPSY-ZACQAIPSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  53
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,4-anhydro-2-deoxy-2-fluoro-3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-4-thio-D-arabinitol 在 吡啶 、 四丁基氟化铵 、 臭氧 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 7.0h， 生成 1,4-anhydro-2-deoxy-2-fluoro-3,5-di-O-benzoyl-4-sulfinyl-D-arabinitol
  参考文献：
  名称：

  Synthesis and Conformational Analysis of 2‘-Fluoro-5-methyl-4‘-thioarabinouridine (4‘S-FMAU)

  摘要：

  An improved synthesis of 2'-deoxy-2'-fluoro-5-methyl-4'-thioarabinouridine (4'S-FMAU) is described. Participation of the 3'-O-benzoyl protecting group in the thiosugar precursor influenced the stereochemistry of the N-glycosylation reaction in nonpolar solvents, permitting a higher beta/alpha ratio than previously observed for similar Lewis acid catalyzed glycosylations. Conformational analysis of the nucleoside using (3)J(HH) and (3)J(HF) NMR coupling constants together with the PSEUROT program showed that it adopted a predominantly northern conformation in contrast to 2'-deoxy-2'-fluoro-5-methylarabinouridine (FMAU), whose PSEUROT conformational analysis is presented here for the first time, which showed a dominantly southeast conformation. The sharp conformational switch attained by replacing the ring heteroatom is attributed to a decrease in relevant steric and stereoelectronic effects.

  DOI：

  10.1021/jo051844+
• 作为产物：
  描述：

  (2R,3S,4S)-2-(hydroxymethyl)tetrahydrothiophene-3,4-diol 在 吡啶 、 4,4'-二氨基二苯乙烯-2,2'-二磺酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.25h， 生成 1,4-anhydro-2-deoxy-2-fluoro-3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-4-thio-D-arabinitol
  参考文献：
  名称：

  Synthesis and Conformational Analysis of 2‘-Fluoro-5-methyl-4‘-thioarabinouridine (4‘S-FMAU)

  摘要：

  An improved synthesis of 2'-deoxy-2'-fluoro-5-methyl-4'-thioarabinouridine (4'S-FMAU) is described. Participation of the 3'-O-benzoyl protecting group in the thiosugar precursor influenced the stereochemistry of the N-glycosylation reaction in nonpolar solvents, permitting a higher beta/alpha ratio than previously observed for similar Lewis acid catalyzed glycosylations. Conformational analysis of the nucleoside using (3)J(HH) and (3)J(HF) NMR coupling constants together with the PSEUROT program showed that it adopted a predominantly northern conformation in contrast to 2'-deoxy-2'-fluoro-5-methylarabinouridine (FMAU), whose PSEUROT conformational analysis is presented here for the first time, which showed a dominantly southeast conformation. The sharp conformational switch attained by replacing the ring heteroatom is attributed to a decrease in relevant steric and stereoelectronic effects.

  DOI：

  10.1021/jo051844+

文献信息

• Synthesis of 2-deoxy-2-fluoro and 1,2-ene derivatives of the naturally occurring glycosidase inhibitor, salacinol, and their inhibitory activities against recombinant human maltase glucoamylase
  作者：Niloufar Choubdar、Lyann Sim、David R. Rose、B. Mario Pinto

  DOI：10.1016/j.carres.2008.01.025

  日期：2008.4

  2-Deoxy-2-fluorosalacinol and a 1,2-ene derivative of the naturally occurring glycosidase inhibitor salacinol were synthesized for structure activity studies with human maltase glucoamylase (MGA). 2-Deoxy-2-fluorosalacinol was synthesized through the coupling reaction of 2-deoxy-2-fluoro-3,5-di-O-p-methoxybenzyl-1,4-anhydro-4-thio-D-arabinitol with 2,4-O-benzylidene-L-crythritol-1,3-cyclic sulfate in hexafluoroisopropanol (HFIP) containing 0.3 equiv of K2CO3. Excess of K2CO3 resulted in the elimination of HF from the coupled product, and the formation of an alkene derivative of salacinol. Nucleophilic attack of the 1,4-anhydro-4-thio-D-arabinitol moiety on the cyclic sulfate did not proceed in the absence of K2CO3. No reaction was observed in acetonitrile containing K2CO3. The target compounds were obtained by deprotection with TFA. The 2-deoxy-1-ene derivative of salacinol and 2-deoxy-2-fluorosalacinol inhibited recombinant human maltase glucoamylase, one of the key intestinal enzymes involved in the breakdown of glucose, with an IC50 value of 150 mu M and a K-i value of 6 +/- 1 mu M, respectively. (C) 2008 Elsevier Ltd. All rights reserved.
• Synthesis and Conformational Analysis of 2‘-Fluoro-5-methyl-4‘-thioarabinouridine (4‘S-FMAU)
  作者：Jonathan K. Watts、Kashinath Sadalapure、Niloufar Choubdar、B. Mario Pinto、Masad J. Damha

  DOI：10.1021/jo051844+

  日期：2006.2.1

  An improved synthesis of 2'-deoxy-2'-fluoro-5-methyl-4'-thioarabinouridine (4'S-FMAU) is described. Participation of the 3'-O-benzoyl protecting group in the thiosugar precursor influenced the stereochemistry of the N-glycosylation reaction in nonpolar solvents, permitting a higher beta/alpha ratio than previously observed for similar Lewis acid catalyzed glycosylations. Conformational analysis of the nucleoside using (3)J(HH) and (3)J(HF) NMR coupling constants together with the PSEUROT program showed that it adopted a predominantly northern conformation in contrast to 2'-deoxy-2'-fluoro-5-methylarabinouridine (FMAU), whose PSEUROT conformational analysis is presented here for the first time, which showed a dominantly southeast conformation. The sharp conformational switch attained by replacing the ring heteroatom is attributed to a decrease in relevant steric and stereoelectronic effects.