(3aR,6S,6aR)-6-(methanesulfonyl)tetrahydro-2,2,4-trimethylfuro[3,4-d]-1,3-dioxol-4-ol

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3aR,6S,6aR)-6-(methanesulfonyl)tetrahydro-2,2,4-trimethylfuro[3,4-d]-1,3-dioxol-4-ol
• 英文别名: 1-methyl-5-O-methanesulfonyl-2,3-O-isopropylidene-L-lyxose；(3aR,4S,6aR)-methanesulfonic acid 6-hydroxy-2,2,6-trimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl ester；(3aR, 4S, 6aR)-methanesulfonic acid 6-hydroxy-2,2,6-trimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl ester；[(3aR,6S,6aR)-4-hydroxy-2,2,4-trimethyl-6,6a-dihydro-3aH-furo[3,4-d][1,3]dioxol-6-yl]methyl methanesulfonate
• 化学式: C₁₀H₁₈O₇S
• 分子量: 282.315
• InChiKey: VLWKLANVWRXYCN-ZYPUDGPYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  99.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3aR,6S,6aR)-6-(methanesulfonyl)tetrahydro-2,2,4-trimethylfuro[3,4-d]-1,3-dioxol-4-ol 在 氨 作用下， 以 乙醇 为溶剂， 以34%的产率得到(2S,3R,4R)-1-methyl-2,3-isopropylidenedioxy-4-hydroxymethyl-1-pyrroline
  参考文献：
  名称：

  exo-Imino to endo-Iminocyclitol Rearrangement. A General Route to Five-Membered Antiviral Azasugars

  摘要：

  A facile synthesis is reported for five-membered iminocyclitols which allows for variation in stereochemistry at all the chiral centers, diverse C-1- and N-substitution, and the potential for a three-component combinatorial process. The key step is inversion at the C-4 stereocenter (L-lyxo sugar -> D-ribono azasugar). The exo-imino to endo-iminocyclitol process was extended to the D-lyxo and the D- and L-hexose series. Some analogues were found to be more potent than N-butyl DNJ and N-nonyl DNJ in antiviral activity.

  DOI：

  10.1021/ol061071r
• 作为产物：
  描述：

  2,3-O-异丙亚基-L-来苏糖酸-1,4-内酯 在 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 0.5h， 生成 (3aR,6S,6aR)-6-(methanesulfonyl)tetrahydro-2,2,4-trimethylfuro[3,4-d]-1,3-dioxol-4-ol
  参考文献：
  名称：

  甲基DGJ异亚丙基的简明，经济和非对映选择性合成：用于模拟合成的亚氨基环醇分子核心

  摘要：

  描述了由1 -L-羟内酯2，3-异亚丙基（6）开始的标题化合物的六步合成。合成通过转化获得6到C 5 -三氟甲或C 5 -mesylate图7a或7b中并通过叠氮化钠的位移，得到的C 5叠氮化合物8。添加甲基溴化镁并进行催化氢化，在此期间叠氮化物基团还原为胺，随后进行分子内环化，生成亚胺15。亚胺的选择性还原会立体选择性地生成甲基DGJ异亚丙基（5通过琥珀酸盐分离并用氨进一步中和。发现改变合成顺序，即代替7a → 8 → 9，可以先将甲基溴化镁添加到甲磺酸盐7b，7b → 11中，然后将叠氮化物离子置换11 → 9。从成本，使用甲磺酰氯而不是三氟甲基磺酰氯，操作简便和产率的观点来看，该修饰被证明是有利的。甲基DGJ异亚丙基（5）是一种重要的氮杂糖前体，因为它可以进行N-烷基取代通过还原胺化反应，并在C 2上 通过仲羟基衍生化。本文报道的合成允许产生该重要的关键亚氨基环糖醇核心的多谱图量。

  DOI：

  10.1021/op060100a

文献信息

• [EN] PROCESS FOR THE PREPARATION OF 1,3-DIOXOLO [4,5-C] PIPERIDIN-7-OLS AND RELATED COMPOUNDS<br/>[FR] PROCEDE DE PREPARATION DE 1,3-DIOXOLO [4,5-C] PIPERIDIN-7-OLS ET COMPOSES CONNEXES
  申请人：DELMAR CHEMICALS INC

  公开号：WO2005066181A1

  公开（公告）日：2005-07-21

  A process is disclosed for preparation of piperidine derivatives, preferably 1,3-dioxolo 4,5-c piperidin-7-ols such as (3aS, 4R, 7S, 7aR)-2,2,4-trimethyl-1,3-dioxolo 4,5-c piperidin-7-ol and its polyhydroxylated derivatives. In a preferred process, 2,3-O-isopropylidene-1,4-lactone (A) is reacted with methanesulfonyl chloride to form (3aR, 4S, 6aR) methanesulfonic acid 2,2-dimethyl-6-oxo-tetrahydro-furo 3,4-d 1,3 dioxol-4-ylmethyl (B). Compound (B) is then reacted with methylmagnesium halide to form (3aR, 4S, 6aR)-methanesulfonic acid 6-hydroxy-2,2,6-trimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl ester (C), which is reacted with phthalimide to form (3aR, 4S, 6aR)-2-(6-hydroxy-2,2,6-trimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl)-isoindole-1,3-dione (D). Compound (D) is reacted with hydrazine to form (3S, 7S, 7aR)-2,2,4-trimethyl-3a,6,7,7a-tetrahydro- 1,3 dioxolo 4,5-c pyridin-7-ol (E), which is hydrogenated to give the corresponding 1,3-dioxolo 4,5-c piperidin-7-ol (F). The synthesis has an overall yield which is typically greater than 50% and avoids the use of reagents such as triflic anhydride and sodium azide.

  揭示了一种制备哌啶衍生物的过程，最好是1,3-二氧杂环[4,5-c]哌啶-7-醇，如(3aS, 4R, 7S, 7aR)-2,2,4-三甲基-1,3-二氧杂环[4,5-c]哌啶-7-醇及其多羟基衍生物。在一种首选的过程中，2,3-O-异丙基亚甲酰基-1,4-内酯（A）与甲磺酰氯反应，形成(3aR, 4S, 6aR) 甲磺酸 2,2-二甲基-6-氧代-四氢呋喃[3,4-d][1,3]二噁烷-4-基甲酯（B）。然后，化合物（B）与甲基镁卤化物反应，形成(3aR, 4S, 6aR)-甲磺酸 6-羟基-2,2,6-三甲基-四氢呋喃[3,4-d][1,3]二噁烷-4-基甲酯（C），再与邻苯二甲酰亚胺反应，形成(3aR, 4S, 6aR)-2-(6-羟基-2,2,6-三甲基-四氢呋喃[3,4-d][1,3]二噁烷-4-基甲基)-异吲哚-1,3-二酮（D）。化合物（D）与肼反应，形成(3S, 7S, 7aR)-2,2,4-三甲基-3a,6,7,7a-四氢-1,3-二氧杂环[4,5-c]吡啶-7-醇（E），经过氢化得到相应的1,3-二氧杂环[4,5-c]哌啶-7-醇（F）。该合成的总产率通常大于50%，并避免使用三氟乙酰酐和偏硝基苯胺等试剂。
• Process for the preparation of piperidine derivatives
  申请人：Meunier Jean-Francois

  公开号：US20050176752A1

  公开（公告）日：2005-08-11

  A process is disclosed for preparation of piperidine derivatives, preferably 1,3-dioxolo [4,5-c] piperidin-7-ols such as (3aS, 4R, 7S, 7aR)-2,2,4-trimethyl-1,3-dioxolo [4,5-c] piperidin-7-ol and its polyhydroxylated derivatives. In a preferred process, 2,3-O-isopropylidene-1,4-lactone (A) is reacted with methanesulfonyl chloride to form (3aR, 4S, 6aR) methanesulfonic acid 2,2-dimethyl-6-oxo-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl (B). Compound (B) is then reacted with methylmagnesium halide to form (3aR, 4S, 6aR)-methanesulfonic acid 6-hydroxy-2,2,6-trimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl ester (C), which is reacted with phthalimide to form (3aR, 4S, 6aR)-2-(6-hydroxy-2,2,6-trimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl)-isoindole-1,3-dione (D). Compound (D) is reacted with hydrazine to form (3S, 7S, 7aR)-2,2,4-trimethyl-3a,6,7,7a-tetrahydro-[1,3]dioxolo[4,5-c]pyridin-7-ol (E), which is hydrogenated to give the corresponding 1,3-dioxolo [4,5-c] piperidin-7-ol (F). The synthesis has an overall yield which is typically greater than 50% and avoids the use of reagents such as triflic anhydride and sodium azide.

  本发明揭示了一种制备吡啶衍生物的方法，优选为制备1,3-二氧杂环[4,5-c]吡啶-7-醇，例如(3aS,4R,7S,7aR)-2,2,4-三甲基-1,3-二氧杂环[4,5-c]吡啶-7-醇及其多羟基衍生物。在优选的方法中，2,3-O-异丙基-1,4-内酯(A)与甲磺酰氯反应，形成(3aR,4S,6aR)-甲磺酸2,2-二甲基-6-氧代四氢呋[3,4-d][1,3]二噁烷-4-基甲酯(B)。化合物(B)然后与甲基镁卤反应，形成(3aR,4S,6aR)-甲磺酸6-羟基-2,2,6-三甲基-四氢呋[3,4-d][1,3]二噁烷-4-基甲酯(C)，它与邻苯二甲酰亚胺反应形成(3aR,4S,6aR)-2-(6-羟基-2,2,6-三甲基-四氢呋[3,4-d][1,3]二噁烷-4-基甲基)-异吲哚-1,3-二酮(D)。化合物(D)与肼反应形成(3S,7S,7aR)-2,2,4-三甲基-3a,6,7,7a-四氢-[1,3]二氧杂环[4,5-c]吡啶-7-醇(E)，它经氢化反应得到相应的1,3-二氧杂环[4,5-c]吡啶-7-醇(F)。该合成方法的总收率通常大于50％，避免使用三氟乙酰酐和偏氮化钠等试剂。
• <i>exo</i>-Imino to <i>endo</i>-Iminocyclitol Rearrangement. A General Route to Five-Membered Antiviral Azasugars
  作者：Robert M. Moriarty、Carmen I. Mitan、Norica Branzǎ-Nichita、Kenneth R. Phares、Damon Parrish

  DOI：10.1021/ol061071r

  日期：2006.8.1

  A facile synthesis is reported for five-membered iminocyclitols which allows for variation in stereochemistry at all the chiral centers, diverse C-1- and N-substitution, and the potential for a three-component combinatorial process. The key step is inversion at the C-4 stereocenter (L-lyxo sugar -> D-ribono azasugar). The exo-imino to endo-iminocyclitol process was extended to the D-lyxo and the D- and L-hexose series. Some analogues were found to be more potent than N-butyl DNJ and N-nonyl DNJ in antiviral activity.
• A Concise, Economical, and Diastereoselective Synthesis of Methyl DGJ Isopropylidene:  An Iminocyclitol Molecule Core for Analogue Synthesis
  作者：Hitesh Batra、Robert M. Moriarty、Raju Penmasta、Vijay Sharma、Gabriela Stancuic、James P. Staszewski、Sudersan M. Tuladhar、David A. Walsh

  DOI：10.1021/op060100a

  日期：2006.9.1

  that changing the synthetic sequence, namely, instead of 7a → 8 → 9, the methylmagnesium bromide could be added first to the mesylate 7b, 7b → 11 followed by azide ion displacement 11 → 9. This modification proved advantageous from the viewpoint of cost, use of methanesulfonyl chloride rather than trifluoromethylsulfonyl chloride, ease of operation, and yield. Methyl DGJ isopropylidene (5) is an important

  描述了由1 -L-羟内酯2，3-异亚丙基（6）开始的标题化合物的六步合成。合成通过转化获得6到C 5 -三氟甲或C 5 -mesylate图7a或7b中并通过叠氮化钠的位移，得到的C 5叠氮化合物8。添加甲基溴化镁并进行催化氢化，在此期间叠氮化物基团还原为胺，随后进行分子内环化，生成亚胺15。亚胺的选择性还原会立体选择性地生成甲基DGJ异亚丙基（5通过琥珀酸盐分离并用氨进一步中和。发现改变合成顺序，即代替7a → 8 → 9，可以先将甲基溴化镁添加到甲磺酸盐7b，7b → 11中，然后将叠氮化物离子置换11 → 9。从成本，使用甲磺酰氯而不是三氟甲基磺酰氯，操作简便和产率的观点来看，该修饰被证明是有利的。甲基DGJ异亚丙基（5）是一种重要的氮杂糖前体，因为它可以进行N-烷基取代通过还原胺化反应，并在C 2上 通过仲羟基衍生化。本文报道的合成允许产生该重要的关键亚氨基环糖醇核心的多谱图量。