(3S,4R,5R)-4,5-bis(hydroxymethyl)oxolan-3-ol | 201278-46-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧唑烯
• 英文名称: (3S,4R,5R)-4,5-bis(hydroxymethyl)oxolan-3-ol
• CAS: 201278-46-8
• 化学式: C₆H₁₂O₄
• 分子量: 148.159
• InChiKey: JJJKAPIPGHXDHR-PBXRRBTRSA-N

物化性质

• 沸点：
  358.6±17.0 °C(Predicted)
• 密度：
  1.300±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  69.9
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3S,4R,5R)-4,5-bis(hydroxymethyl)oxolan-3-ol 在 吡啶 、 4-二甲氨基吡啶 、 18-冠醚-6 、 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 54.0h， 生成 9-[(3R,4S,5R)-4,5-bis[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-3-yl]purin-6-amine
  参考文献：
  名称：

  Synthesis of Methylene-Expanded Oxetanocin Isonucleosides in Both Enantiomeric Forms¹

  摘要：

  We report a novel route to isonucleosides of the 'methylene-expanded' oxetanocin class, in both the D-and L-enantiomeric forms, e.g., compounds L-(+)-2a, D-(-)-2a, and L-(-)-2b, beginning with the simple, known mono-p-bromobenzyl ether 3 of the very inexpensive 2-butene-1,4-diol. Sharpless asymmetric epoxidation of 3 gave either (-) or (+)-4 depending on the chirality of the tartrate used. The p-bromobenzyl ether was used since the epoxide product is crystalline and can be recrystallized to high optical purity. Opening of the epoxide with vinylmagnesium bromide gave the 1,3-diol 5, the primary alcohol of which was protected as the silyl ether 6. Treatment of 6 with iodonium bis(sym-collidine) perchlorate afforded the desired 5-(iodomethyl)tetrahydrofuran-3-ol 8 with loss of the bromobenzyl cation in the key step in the synthetic scheme. This iodide 8 was then converted into the bis(silyloxy)-protected alcohol 15 by acetylation to give the acetate 10, displacement of iodide with acetate, hydrolysis, and selective protection of the primary alcohols. The alcohol 6 could also be converted into 15 via initial acetylation and then iodocyclization to give 10. The diol 5 could also be converted into 15 by a similar route involving bis-acetylation and iodocyclization followed by functional group transformations. The tosylate of 15 was displaced with the anion of adenine or thymidine to give, alter final desilylation, the desired isonucleosides-the D-adenosine analogue (-)-2a and the L-adenosine and thymidine analogues (+)-2a and(-)-2b. All of the stereochemistry of the final products is derived from the first step of the synthesis, namely, the Sharpless asymmetric epoxidation of 3. The biological activity of the new compounds L-(+)-2a and L-(-)-2b against HIV was determined in the anti-HIV drug-testing system of the National Cancer Institute. The adenosine analogue L-(+)-2a was inactive in this screen, while the thymidine analogue L-(-)-2b showed moderate anti-HIV activity (IC50 > 2 x 10(-4) M, EC50 = 8 x 10(-7) M, TI50 > 250).

  DOI：

  10.1021/jo971890c
• 作为产物：
  描述：

  [(2R,3S,4S)-4-acetyloxy-2-(acetyloxymethyl)oxolan-3-yl]methyl acetate 在 氨 作用下， 以 甲醇 为溶剂， 生成 (3S,4R,5R)-4,5-bis(hydroxymethyl)oxolan-3-ol
  参考文献：
  名称：

  Synthesis of Methylene-Expanded Oxetanocin Isonucleosides in Both Enantiomeric Forms¹

  摘要：

  We report a novel route to isonucleosides of the 'methylene-expanded' oxetanocin class, in both the D-and L-enantiomeric forms, e.g., compounds L-(+)-2a, D-(-)-2a, and L-(-)-2b, beginning with the simple, known mono-p-bromobenzyl ether 3 of the very inexpensive 2-butene-1,4-diol. Sharpless asymmetric epoxidation of 3 gave either (-) or (+)-4 depending on the chirality of the tartrate used. The p-bromobenzyl ether was used since the epoxide product is crystalline and can be recrystallized to high optical purity. Opening of the epoxide with vinylmagnesium bromide gave the 1,3-diol 5, the primary alcohol of which was protected as the silyl ether 6. Treatment of 6 with iodonium bis(sym-collidine) perchlorate afforded the desired 5-(iodomethyl)tetrahydrofuran-3-ol 8 with loss of the bromobenzyl cation in the key step in the synthetic scheme. This iodide 8 was then converted into the bis(silyloxy)-protected alcohol 15 by acetylation to give the acetate 10, displacement of iodide with acetate, hydrolysis, and selective protection of the primary alcohols. The alcohol 6 could also be converted into 15 via initial acetylation and then iodocyclization to give 10. The diol 5 could also be converted into 15 by a similar route involving bis-acetylation and iodocyclization followed by functional group transformations. The tosylate of 15 was displaced with the anion of adenine or thymidine to give, alter final desilylation, the desired isonucleosides-the D-adenosine analogue (-)-2a and the L-adenosine and thymidine analogues (+)-2a and(-)-2b. All of the stereochemistry of the final products is derived from the first step of the synthesis, namely, the Sharpless asymmetric epoxidation of 3. The biological activity of the new compounds L-(+)-2a and L-(-)-2b against HIV was determined in the anti-HIV drug-testing system of the National Cancer Institute. The adenosine analogue L-(+)-2a was inactive in this screen, while the thymidine analogue L-(-)-2b showed moderate anti-HIV activity (IC50 > 2 x 10(-4) M, EC50 = 8 x 10(-7) M, TI50 > 250).

  DOI：

  10.1021/jo971890c

文献信息

• Synthesis of Methylene-Expanded Oxetanocin Isonucleosides in Both Enantiomeric Forms¹
  作者：Michael E. Jung、Christopher J. Nichols

  DOI：10.1021/jo971890c

  日期：1998.1.1

  We report a novel route to isonucleosides of the 'methylene-expanded' oxetanocin class, in both the D-and L-enantiomeric forms, e.g., compounds L-(+)-2a, D-(-)-2a, and L-(-)-2b, beginning with the simple, known mono-p-bromobenzyl ether 3 of the very inexpensive 2-butene-1,4-diol. Sharpless asymmetric epoxidation of 3 gave either (-) or (+)-4 depending on the chirality of the tartrate used. The p-bromobenzyl ether was used since the epoxide product is crystalline and can be recrystallized to high optical purity. Opening of the epoxide with vinylmagnesium bromide gave the 1,3-diol 5, the primary alcohol of which was protected as the silyl ether 6. Treatment of 6 with iodonium bis(sym-collidine) perchlorate afforded the desired 5-(iodomethyl)tetrahydrofuran-3-ol 8 with loss of the bromobenzyl cation in the key step in the synthetic scheme. This iodide 8 was then converted into the bis(silyloxy)-protected alcohol 15 by acetylation to give the acetate 10, displacement of iodide with acetate, hydrolysis, and selective protection of the primary alcohols. The alcohol 6 could also be converted into 15 via initial acetylation and then iodocyclization to give 10. The diol 5 could also be converted into 15 by a similar route involving bis-acetylation and iodocyclization followed by functional group transformations. The tosylate of 15 was displaced with the anion of adenine or thymidine to give, alter final desilylation, the desired isonucleosides-the D-adenosine analogue (-)-2a and the L-adenosine and thymidine analogues (+)-2a and(-)-2b. All of the stereochemistry of the final products is derived from the first step of the synthesis, namely, the Sharpless asymmetric epoxidation of 3. The biological activity of the new compounds L-(+)-2a and L-(-)-2b against HIV was determined in the anti-HIV drug-testing system of the National Cancer Institute. The adenosine analogue L-(+)-2a was inactive in this screen, while the thymidine analogue L-(-)-2b showed moderate anti-HIV activity (IC50 > 2 x 10(-4) M, EC50 = 8 x 10(-7) M, TI50 > 250).