O,O-diethyl (3R,4R)-3-[(tert-butoxycarbonyl)amino]-1,1-difluoro-4-hydroxy-4-phenylbutylphosphonothioate | 1178980-64-7

• 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: O,O-diethyl (3R,4R)-3-[(tert-butoxycarbonyl)amino]-1,1-difluoro-4-hydroxy-4-phenylbutylphosphonothioate
• 英文别名: tert-butyl N-[(1R,2R)-4-diethoxyphosphinothioyl-4,4-difluoro-1-hydroxy-1-phenylbutan-2-yl]carbamate
• CAS: 1178980-64-7
• 化学式: C₁₉H₃₀F₂NO₅PS
• 分子量: 453.487
• InChiKey: SHVNKEROTFHCER-HZPDHXFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 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：
  109
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  O,O-diethyl (3R,4R)-3-[(tert-butoxycarbonyl)amino]-1,1-difluoro-4-hydroxy-4-phenylbutylphosphonothioate 、 N,N'-羰基二咪唑 在 三氟乙酸 、 N-甲基吗啉 作用下， 以 二氯甲烷 、 四氢呋喃 为溶剂， 反应 14.0h， 以28%的产率得到O,O-diethyl 1,1-difluoro-2-[(4R,5R)-2-oxo-5-phenyl-1,3-oxazolidin-4-yl]ethylphosphonothioate
  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]-1,1-difluoro-4-oxo-4-phenylbutylphosphonothioate 在 L-Selectride 、 柠檬酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 以71%的产率得到O,O-diethyl (3R,4R)-3-[(tert-butoxycarbonyl)amino]-1,1-difluoro-4-hydroxy-4-phenylbutylphosphonothioate
  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.