(2R,4S,5R)-2-benzyl-3,4-dimethyl-2-oxo-5-phenyl-1,3,2λ⁵-oxazaphospholidine | 278605-33-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2R,4S,5R)-2-benzyl-3,4-dimethyl-2-oxo-5-phenyl-1,3,2λ⁵-oxazaphospholidine
• 英文别名: (2R,4S,5R)-2-benzyl-3,4-dimethyl-5-phenyl-1,3,2lambda5-oxazaphospholidine 2-oxide；(2R,4S,5R)-2-benzyl-3,4-dimethyl-5-phenyl-1,3,2λ5-oxazaphospholidine 2-oxide
• CAS: 278605-33-7
• 化学式: C₁₇H₂₀NO₂P
• 分子量: 301.325
• InChiKey: HSYYOOOMAJSUTR-XXHMAFKTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2R,4S,5R)-2-benzyl-3,4-dimethyl-2-oxo-5-phenyl-1,3,2λ⁵-oxazaphospholidine 在 dirhodium tetraacetate lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 5.5h， 生成 (2R,4S,5R)-2-[(α-benzyloxycarbonyl)aminobenzyl]-3,4-dimethyl-2-oxo-5-phenyl-1,3,2λ⁵-oxazaphospholidine
  参考文献：
  名称：

  Preparation of chiral α-diazophosphonic acid derivatives

  摘要：

  The chiral alpha -diazophosphonic acid derivatives 3. 6 and 8 were prepared from (-)ephedrine and (S,S)-N,N ' -dimethyl-1,2-diaminocyclohexane; preliminary experiments suggest that the chiral auxiliary exerts little influence in the dirhodium(il) acetate catalysed O-H and N-H insertion reactions. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(01)00287-7
• 作为产物：
  描述：

  苄基磷酸 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 4.0h， 生成 (2R,4S,5R)-2-benzyl-3,4-dimethyl-2-oxo-5-phenyl-1,3,2λ⁵-oxazaphospholidine
  参考文献：
  名称：

  Preparation of chiral α-monofluoroalkylphosphonic acids and their evaluation as inhibitors of protein tyrosine phosphatase 1B

  摘要：

  通过对以(â)-麻黄碱为手性助剂的不对称磷酰胺酸的δ-碳酰离子进行非对映选择性亲电氟化，合成了对映体纯的δ-一氟烷基膦酸4â9。氟化反应的非对映过量在很大程度上取决于碱和反离子的性质，脱氧率在 2%-72% 之间。通过柱层析法获得了非对映纯的δ±-氟磷酰胺酸盐。通过 X 射线晶体学确定了氟化膦酰酰胺酸盐的绝对立体化学结构。用 MeOHâTFA 除去麻黄碱助剂，然后用 TMSBr 处理，得到了δ-单氟烷基膦酸 4â9 ，产率为中等至良好。在手性碱奎尼丁存在下对手性膦酸 4â9 进行的 19F-NMR 分析表明，膦酸的ee值大于 97%。用 4â9 和蛋白酪氨酸磷酸酶 1B (PTP1B) 进行的抑制研究表明，R-对映体的抑制作用比相应的 S-对映体强约 10 倍，但比δ,δ-二氟类似物低 10 倍。本文讨论了造成这些差异的可能原因。

  DOI：

  10.1039/a908086d

文献信息

• Preparation of chiral α-monofluoroalkylphosphonic acids and their evaluation as inhibitors of protein tyrosine phosphatase 1B
  作者：Christopher C. Kotoris、Wendy Wen、Alan Lough、Scott D. Taylor

  DOI：10.1039/a908086d

  日期：——

  Enantiomerically pure α-monofluoroalkylphosphonic acids 4–9 were synthesized by diastereoselective electrophilic fluorination of α-carbanions of asymmetric phosphonamidates bearing (−)-ephedrine as a chiral auxiliary. The diastereomeric excess of the fluorination reaction was highly dependent on the nature of the base and counterion with de’s ranging from 2–72%. Diastereomerically pure α-fluorophosphonamidates were obtained by column chromatography. The absolute stereochemistry of the fluorinated phosphonamidates was established by X-ray crystallography. Removal of the ephedrine auxiliary using MeOH–TFA followed by treatment with TMSBr afforded α-monofluoroalkylphosphonic acids 4–9 in modest to good yields. 19F-NMR analysis of the chiral phosphonic acids 4–9 in the presence of the chiral base quinidine indicated that the phosphonic acids were obtained in greater than 97% ee. Inhibition studies with 4–9 and protein tyrosine phosphatase 1B (PTP1B) revealed that the R-enantiomers were approximately 10-fold more potent inhibitors than the corresponding S-enantiomers, but 10-fold less potent than their α,α-difluoro analogues. Possible reasons for these differences are discussed.

  通过对以(â)-麻黄碱为手性助剂的不对称磷酰胺酸的δ-碳酰离子进行非对映选择性亲电氟化，合成了对映体纯的δ-一氟烷基膦酸4â9。氟化反应的非对映过量在很大程度上取决于碱和反离子的性质，脱氧率在 2%-72% 之间。通过柱层析法获得了非对映纯的δ±-氟磷酰胺酸盐。通过 X 射线晶体学确定了氟化膦酰酰胺酸盐的绝对立体化学结构。用 MeOHâTFA 除去麻黄碱助剂，然后用 TMSBr 处理，得到了δ-单氟烷基膦酸 4â9 ，产率为中等至良好。在手性碱奎尼丁存在下对手性膦酸 4â9 进行的 19F-NMR 分析表明，膦酸的ee值大于 97%。用 4â9 和蛋白酪氨酸磷酸酶 1B (PTP1B) 进行的抑制研究表明，R-对映体的抑制作用比相应的 S-对映体强约 10 倍，但比δ,δ-二氟类似物低 10 倍。本文讨论了造成这些差异的可能原因。
• Preparation of chiral α-diazophosphonic acid derivatives
  作者：Christopher J. Moody、C.Neil Morfitt、Alexandra M.Z. Slawin

  DOI：10.1016/s0957-4166(01)00287-7

  日期：2001.7

  The chiral alpha -diazophosphonic acid derivatives 3. 6 and 8 were prepared from (-)ephedrine and (S,S)-N,N ' -dimethyl-1,2-diaminocyclohexane; preliminary experiments suggest that the chiral auxiliary exerts little influence in the dirhodium(il) acetate catalysed O-H and N-H insertion reactions. (C) 2001 Elsevier Science Ltd. All rights reserved.