Methyl (2S)-2-<<(tert-butyldimethylsilyl)oxy>lactyl>-trans-4-hydroxy-L-prolinate | 161708-31-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Methyl (2S)-2-<<(tert-butyldimethylsilyl)oxy>lactyl>-trans-4-hydroxy-L-prolinate
• 英文别名: methyl (2S,4R)-1-[(2S)-2-[tert-butyl(dimethyl)silyl]oxypropanoyl]-4-hydroxypyrrolidine-2-carboxylate
• CAS: 161708-31-2
• 化学式: C₁₅H₂₉NO₅Si
• 分子量: 331.484
• InChiKey: KHKIXMGEHZGLRJ-TUAOUCFPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.53
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Methyl (2S)-2-<<(tert-butyldimethylsilyl)oxy>lactyl>-trans-4-hydroxy-L-prolinate 在 N-甲基吗啉 、 吡啶 、 4-二甲氨基吡啶 、 lithium hydroxide 、 sodium tetrahydroborate 、 四丁基氟化铵 、 双氧水 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 31.5h， 生成 (R)-2-{[(S)-1-((S)-2-Hydroxy-propionyl)-2,5-dihydro-1H-pyrrole-2-carbonyl]-methyl-amino}-4-methyl-pentanoic acid
  参考文献：
  名称：

  Synthesis of New Didemnin B Analogs for Investigations of Structure/Biological Activity Relationships

  摘要：

  Modifications were introduced in the side chain of didemnin B to afford several analogs (1f-1j) for biological testing in order to identify the features responsible for the bioactivity of the natural products (1a-1c). To achieve our goal, two changes were made in the proline ring of the beta-turn side chain. Initially, a hydroxyl group was incorporated at the C-4 position of the ring to increase the polar nature of the molecule. Secondly, unsaturation was introduced at C-3 and C-4 to increase the rigidity of the ring and to provide a site for tritiation to follow the drug pathway in biological systems. Improvements were also introduced in the macrocycle construction to produce gram quantities of this unit (1d) for the preparation of the planned analogs. The linear precursor to the macrocycle was oxidized more effectively with 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (Dess-Martin periodinane reagent), and cyclization yields were increased substantially by using a new coupling reagent, pentafluorophenyl diphenylphosphinate (FDPP). (1H-1,2,3-benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and pentafluorophenyl trifluoroacetate were also used to improve other coupling reactions.

  DOI：

  10.1021/jo00097a022
• 作为产物：
  描述：

  (s)-(-)-2-(叔丁基二甲基甲硅烷基氧基)丙酸乙酯 在 N-甲基吗啉 、 lithium hydroxide 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 9.5h， 生成 Methyl (2S)-2-<<(tert-butyldimethylsilyl)oxy>lactyl>-trans-4-hydroxy-L-prolinate
  参考文献：
  名称：

  Synthesis of New Didemnin B Analogs for Investigations of Structure/Biological Activity Relationships

  摘要：

  Modifications were introduced in the side chain of didemnin B to afford several analogs (1f-1j) for biological testing in order to identify the features responsible for the bioactivity of the natural products (1a-1c). To achieve our goal, two changes were made in the proline ring of the beta-turn side chain. Initially, a hydroxyl group was incorporated at the C-4 position of the ring to increase the polar nature of the molecule. Secondly, unsaturation was introduced at C-3 and C-4 to increase the rigidity of the ring and to provide a site for tritiation to follow the drug pathway in biological systems. Improvements were also introduced in the macrocycle construction to produce gram quantities of this unit (1d) for the preparation of the planned analogs. The linear precursor to the macrocycle was oxidized more effectively with 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (Dess-Martin periodinane reagent), and cyclization yields were increased substantially by using a new coupling reagent, pentafluorophenyl diphenylphosphinate (FDPP). (1H-1,2,3-benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and pentafluorophenyl trifluoroacetate were also used to improve other coupling reactions.

  DOI：

  10.1021/jo00097a022