diethyl (3R,4S)-1,1-difluoro-4-hydroxy-3-([pentadecylcarbonyl]amino)-4-phenylbutylphosphonate | 528523-57-1

• 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)-1,1-difluoro-4-hydroxy-3-([pentadecylcarbonyl]amino)-4-phenylbutylphosphonate
• 英文别名: diethyl (3R,4S)-1,1-difluoro-4-hydroxy-3-(palmitoylamino)-4-phenylbutylphosphonate；N-[(1S,2R)-4-[diethoxy(oxido)phosphaniumyl]-4,4-difluoro-1-hydroxy-1-phenylbutan-2-yl]hexadecanamide
• CAS: 528523-57-1
• 化学式: C₃₀H₅₂F₂NO₅P
• 分子量: 575.717
• InChiKey: FYLJRFFVNUSZCH-PXJZQJOASA-N

物化性质

• 沸点：
  678.3±55.0 °C(predicted)
• 密度：
  1.070±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.9
• 重原子数：
  39
• 可旋转键数：
  24
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  90.8
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  diethyl (3R,4S)-1,1-difluoro-4-hydroxy-3-([pentadecylcarbonyl]amino)-4-phenylbutylphosphonate 在 三甲基溴硅烷 作用下， 以 二氯甲烷 、 甲醇 为溶剂， 反应 26.0h， 生成 (3R,4S)-1,1-difluoro-4-hydroxy-3-(palmitoylamino)-4-phenylbutylphosphonic acid
  参考文献：
  名称：

  Synthesis of non-competitive inhibitors of Sphingomyelinases with significant activity

  摘要：

  A series of short-chain analogues of N-palmitoylsphingosine-1-phosphate, modified by replacement of the phosphate and the long alkenyl side chain with hydrolytically stable difluoromethylene phosphonate and phenyl, respectively, were prepared to study the structure-activity relationship for inhibition of sphingomyelinase. The study revealed that inhibition is highly dependent upon the stereochemistry of the asymmetric centers of the acylamino, moiety, and resulted in identification of a non-competitive inhibitor with the same level of inhibitory activity of schyphostatin, the most potent of the few known small molecular inhibitors of sphingomyelinase. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00888-0
• 作为产物：
  描述：

  (1R,2R)-(-)-2-氨基-1-苯基-1,3-丙二醇 在 咪唑 、 盐酸 、 4-二甲氨基吡啶 、 正丁基锂 、 偶氮二异丁腈 、 偶氮二甲酸二异丙酯 、 四丁基氟化铵 、 三正丁基氢锡 、 二异丁基氢化铝 、 戴斯-马丁氧化剂 、 对甲苯磺酸 、 三乙胺 、 三苯基膦 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 、 苯 为溶剂， 反应 47.25h， 生成 diethyl (3R,4S)-1,1-difluoro-4-hydroxy-3-([pentadecylcarbonyl]amino)-4-phenylbutylphosphonate
  参考文献：
  名称：

  Synthesis of non-competitive inhibitors of Sphingomyelinases with significant activity

  摘要：

  A series of short-chain analogues of N-palmitoylsphingosine-1-phosphate, modified by replacement of the phosphate and the long alkenyl side chain with hydrolytically stable difluoromethylene phosphonate and phenyl, respectively, were prepared to study the structure-activity relationship for inhibition of sphingomyelinase. The study revealed that inhibition is highly dependent upon the stereochemistry of the asymmetric centers of the acylamino, moiety, and resulted in identification of a non-competitive inhibitor with the same level of inhibitory activity of schyphostatin, the most potent of the few known small molecular inhibitors of sphingomyelinase. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00888-0

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.