O,O-diethyl (3R)-3-[(tert-butoxycarbonyl)amino]-4-cyclohexyl-1,1-difluoro-4-oxobutylphosphonothioate | 1178980-56-7

• 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: O,O-diethyl (3R)-3-[(tert-butoxycarbonyl)amino]-4-cyclohexyl-1,1-difluoro-4-oxobutylphosphonothioate
• 英文别名: tert-butyl N-[(2R)-1-cyclohexyl-4-diethoxyphosphinothioyl-4,4-difluoro-1-oxobutan-2-yl]carbamate
• CAS: 1178980-56-7
• 化学式: C₁₉H₃₄F₂NO₅PS
• 分子量: 457.519
• InChiKey: RKLJUIBVZUUXRI-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  O,O-diethyl (3R)-3-[(tert-butoxycarbonyl)amino]-4-cyclohexyl-1,1-difluoro-4-oxobutylphosphonothioate 在 乙醇 、 lithium tri-t-butoxyaluminum hydride 、 柠檬酸 作用下， 以 水 为溶剂， 反应 0.5h， 以85%的产率得到O,O-diethyl (3R,4S)-3-[(tert-butoxycarbonyl)amino]-4-cyclohexyl-1,1-difluoro-4-hydroxybutylphosphonothioate
  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：

  O,O-diethyl (3R)-3-[(tert-butoxycarbonyl)amino]-4-cyclohexyl-1,1-difluoro-4-hydroxybutylphosphonothioate 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以160 mg的产率得到O,O-diethyl (3R)-3-[(tert-butoxycarbonyl)amino]-4-cyclohexyl-1,1-difluoro-4-oxobutylphosphonothioate
  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