diethyl (3R,4S)-3-[(tert-butoxycarbonyl)amino]-1,1-difluoro-4-hydroxy-4-phenylbutylphosphonate | 1178980-70-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: diethyl (3R,4S)-3-[(tert-butoxycarbonyl)amino]-1,1-difluoro-4-hydroxy-4-phenylbutylphosphonate
• 英文别名: tert-butyl N-[(1S,2R)-4-diethoxyphosphoryl-4,4-difluoro-1-hydroxy-1-phenylbutan-2-yl]carbamate
• CAS: 1178980-70-5
• 化学式: C₁₉H₃₀F₂NO₆P
• 分子量: 437.421
• InChiKey: PNCRSZHCFUXFIQ-CVEARBPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  94.1
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  diethyl (3R,4S)-3-[(tert-butoxycarbonyl)amino]-1,1-difluoro-4-hydroxy-4-phenylbutylphosphonate 、 棕榈酰氯 在 三氟乙酸 、 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以69%的产率得到diethyl (3R,4S)-1,1-difluoro-4-hydroxy-3-([pentadecylcarbonyl]amino)-4-phenylbutylphosphonate
  参考文献：
  名称：

  Diastereoselective Synthesis of γ-Amino-δ-hydroxy-α,α-difluorophosphonates: A Vehicle for Structure−activity Relationship Studies on SMA-7, a Potent Sphingomyelinase Inhibitor

  摘要：

  A highly diastereoselective synthesis of 2-amino alcohol derivatives bearing a difluoromethylphosphonothioate group at the 3-position was achieved through LiAlH(O-t-Bu)(3)-mediated reduction of the corresponding alpha-amino ketones. The phosphonothioate moiety of the product was readily converted into the corresponding phosphonate by oxidation with m-CPBA, followed by aqueous workup. The developed methods should be useful for SAR studies of SMA-7, a potent inhibitor of SMases.

  DOI：

  10.1021/jo9008782
• 作为产物：
  描述：

  diethyl (3R,4S)-3-[(tert-butoxycarbonyl)amino]-4-([tert-butyl(dimethyl)silyl]oxy)-1,1-difluoro-4-phenylbutylphosphonate 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.25h， 以95%的产率得到diethyl (3R,4S)-3-[(tert-butoxycarbonyl)amino]-1,1-difluoro-4-hydroxy-4-phenylbutylphosphonate
  参考文献：
  名称：

  Diastereoselective Synthesis of γ-Amino-δ-hydroxy-α,α-difluorophosphonates: A Vehicle for Structure−activity Relationship Studies on SMA-7, a Potent Sphingomyelinase Inhibitor

  摘要：

  A highly diastereoselective synthesis of 2-amino alcohol derivatives bearing a difluoromethylphosphonothioate group at the 3-position was achieved through LiAlH(O-t-Bu)(3)-mediated reduction of the corresponding alpha-amino ketones. The phosphonothioate moiety of the product was readily converted into the corresponding phosphonate by oxidation with m-CPBA, followed by aqueous workup. The developed methods should be useful for SAR studies of SMA-7, a potent inhibitor of SMases.

  DOI：

  10.1021/jo9008782

文献信息

• Diastereoselective Synthesis of γ-Amino-δ-hydroxy-α,α-difluorophosphonates: A Vehicle for Structure−activity Relationship Studies on SMA-7, a Potent Sphingomyelinase Inhibitor
  作者：Takehiro Yamagishi、Shin Muronoi、Sadao Hikishima、Hiroshi Shimeno、Shinji Soeda、Tsutomu Yokomatsu

  DOI：10.1021/jo9008782

  日期：2009.8.21

  A highly diastereoselective synthesis of 2-amino alcohol derivatives bearing a difluoromethylphosphonothioate group at the 3-position was achieved through LiAlH(O-t-Bu)(3)-mediated reduction of the corresponding alpha-amino ketones. The phosphonothioate moiety of the product was readily converted into the corresponding phosphonate by oxidation with m-CPBA, followed by aqueous workup. The developed methods should be useful for SAR studies of SMA-7, a potent inhibitor of SMases.