diethyl <1,1-difluoro-O-3,4-isopropylidene-3(S),4-dihydroxybutyl>phosphonate | 141642-64-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: diethyl <1,1-difluoro-O-3,4-isopropylidene-3(S),4-dihydroxybutyl>phosphonate
• 英文别名: diethyl (S)-difluoro-3,4-dihydroxy-3,4-O-isopropylidenebutylphosphonate；(4S)-4-(2-diethoxyphosphoryl-2,2-difluoroethyl)-2,2-dimethyl-1,3-dioxolane
• CAS: 141642-64-0
• 化学式: C₁₁H₂₁F₂O₅P
• 分子量: 302.255
• InChiKey: HSFDEWXNCNVYHE-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.39
• 重原子数：
  19.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  53.99
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  diethyl <1,1-difluoro-O-3,4-isopropylidene-3(S),4-dihydroxybutyl>phosphonate 在 4-二甲氨基吡啶 、 对甲苯磺酸 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 diethyl <1,1-difluoro-3(S),4-bis(n-hexanoyloxy)butyl>phosphonate
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Phospholipid Analogs as Inhibitors of the Bacterial Phospholipase C from Bacillus cereus

  摘要：

  Enzymes belonging to the phospholipase C (PLC) family hydrolyze the phosphodiester bond of phospholipids to give a diacylglycerol and a phosphorylated head group. The bacterial phospholipase C from Bacillus cereus (PLC(Bc)) has been studied extensively, and there is a wealth of information regarding those structural features that are important for substrate activity. In contrast, there is virtually no data available regarding structure-activity relationships for inhibitors of this enzyme. To address this shortcoming, a series of optically pure analogues of 1,2-dihexanoyl-sn-glycero-3-phosphocholine (2) containing different replacements of the phosphate group were first synthesized including the phosphoramidates 4 and 8, the phosphonate 5, the (difluoromethylene)phosphonate 6, the thiophosphate 7, the diastereomeric phosphorothioates 9 and 10, and the phosphorodithioate 11. Each of these phosphatidylcholine derivatives was tested for inhibitor or substrate activity with PLC(Bc) using the water-soluble phosphatidylcholine 2 as the monomeric substrate. The measurements were conducted below the critical micellar concentrations of both 2 and the inhibitor. Of the analogues, only 7 and 9 underwent observable enzymatic hydrolysis under the assay conditions used. The k(cat) of the (Sp)-phosphorothioate 9 was approximately one-fifth that of 2, and when compared to 2, 7 was hydrolyzed only very slowly by the enzyme. Kinetic studies indicated that the phospholipid analogues tested were competitive inhibitors with increasing K-i's follows: 7 approximate to 11 approximate to 10 < 4 approximate to 8 < 5 approximate to 6.

  DOI：

  10.1021/jo00096a024
• 作为产物：
  描述：

  (R)-(+)-2,2-二甲基-1,3-二氧戊环-4-甲醛 在 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 甲苯 为溶剂， 反应 2.0h， 生成 diethyl <1,1-difluoro-O-3,4-isopropylidene-3(S),4-dihydroxybutyl>phosphonate
  参考文献：
  名称：

  A general method for the synthesis of 1,1-difluoroalkylphosphonates

  摘要：

  A facile method for preparing 1,1-difluoroalkylphosphonates has been developed that features radical deoxygenation of thionocarbonates derived from the adducts formed upon addition of 9 to aldehydes.

  DOI：

  10.1016/s0040-4039(00)74156-6

文献信息

• Monofluorophosphonates as phosphate mimics in bioorganic chemistry: a comparative study of CH2-, CHF- and CF2-phosphonate analogues of sn-glycerol-3-phosphate as substrates for sn-glycerol-3-phosphate dehydrogenase
  作者：Jens Nieschalk、David O'Hagan

  DOI：10.1039/c39950000719

  日期：——

  The synthesis of the cyclohexylammonium salts of 3-(S),4-dihydroxy-1(R,S)-fluorobutylphosphonic acid 3 and 1,1-difluoro-3-(S),4-dihydroxybutylphosphonic acid 4 is reported; 3 is a better substrate for NADH linked sn-glycerol-3-phosphate dehydrogenase than the difluoromethylenephosphonate 4; a comparative study of the CH2-, CHF and CF2- phosphonate analogues of sn-glycerol-3-phosphate is reported.

  报告了 3-(S),4-二羟基-1(R,S)-氟丁基膦酸 3 和 1,1-二氟-3-(S),4-二羟基丁基膦酸 4 的环己胺盐的合成；与二氟甲基膦酸 4 相比，3 是 NADH 链接的炔甘油-3-磷酸脱氢酶的更好底物；报告了对炔甘油-3-磷酸的 CH2-、CHF 和 CF2-膦酸类似物的比较研究。
• Synthesis of monofluoro- and difluoro- methylenephosphonate analogues of sn-glycerol-3-phosphate as substrates for glycerol-3-phosphate dehydrogenase and the X-ray structure of the fluoromethylenephosphonate moiety
  作者：Jens Nieschalk、Andrei S Batsanov、David O'Hagan、Judith Howard

  DOI：10.1016/0040-4020(95)00890-k

  日期：1996.1

  The synthesis of the cyclohexylammonium salts of (1RS, 3S)-3,4-dihydroxy-1-fluorobutylphosphonic acid 3 and (S)-difluoro-3,4-dihydroxybutylphosphonic acid 4 is reported. These compounds are fluorinated phosphonate analogues of sn-glycerol-3-phosphate where the bridging phosphate ester oxygen is replaced by CHF and CF2 respectively. Kinetic studies are presented for oxidation with NADH linked glycerol-3-phosphate

  的环己基的盐的合成（1个RS，3S）-3,4-二羟基-1- fluorobutylphosphonic酸3和（S） -二氟-3,4- dihydroxybutylphosphonic酸4报道。这些化合物是sn-甘油-3-磷酸的氟化膦酸酯类似物，其中桥连的磷酸酯氧分别被CHF和CF 2取代。动力学研究是为了与氧化的NADH联甘油-3-磷酸脱氢酶，其揭示，CHF-膦酸酯3个执行类似于天然底物SN -甘油-3-磷酸，并且比CF更好的基板2 -膦4。该研究还揭示了3（3a和3b）的非对映异构体以不同的速率加工，表明该酶可以区分CHF立体异构中心。描述了2-氨基-1-氟乙基膦酸7的合成和X射线晶体结构，其允许比较CHF-膦酸酯与类似的CH 2-和CF 2-膦酸酯的几何构型。