(4S,5R)-4-fluoro-5-hydroxy-6-<(S)-(4-methylphenyl)sulfinyl>hex-1-ene | 121911-13-5

• 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: (4S,5R)-4-fluoro-5-hydroxy-6-<(S)-(4-methylphenyl)sulfinyl>hex-1-ene
• 英文别名: (2R,3S,S_S)-fluorosulfinyl hexenol；(4S,5R)-4-fluoro-5-hydroxy-6-[(S)-(4-methylphenyl)sulfinyl]hex-1-ene；(2R,3S)-3-fluoro-1-[(S)-(4-methylphenyl)sulfinyl]hex-5-en-2-ol
• CAS: 121911-13-5；121961-08-8；142793-64-4；142793-66-6
• 化学式: C₁₃H₁₇FO₂S
• 分子量: 256.341
• InChiKey: XUGZEPNSUXLLGV-DCGLDWPTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.38
• 重原子数：
  17.0
• 可旋转键数：
  6.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  37.3
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (4S,5R)-4-fluoro-5-hydroxy-6-<(S)-(4-methylphenyl)sulfinyl>hex-1-ene 在 三氟乙酸酐 、 sodium iodide 作用下， 以 丙酮 为溶剂， 反应 0.17h， 以100%的产率得到(4S,5R)-4-fluoro-5-hydroxy-6-<(4-methylphenyl)sulfenyl>hex-1-ene
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of enantiomerically pure 4-deoxy-4-fluoromuscarines

  摘要：

  Four isomers of [(4-fluoro-5-methyl-tetrahydrofuran-2-yl)methyl]trimethylammonium iodide (4-deoxy-4-fluoro-muscarines) were prepared in enantiomerically and diastereomerically pure form from (S)-(-)-methyl 4-methylphenyl sulfoxide, ethyl fluoroacetate, and allyl bromide. Their absolute configurations were assigned by H-1 NMR analyses. The four optically pure compounds were tested in vitro on guinea pig and their muscarinic potency was evaluated at M3 (ileum and bladder) and M2 (heart) muscarinic receptor subtypes. Compound 1a, the most potent isomer of the series, was also tested in vivo on pithed rat and its muscarinic activity at the M1 receptor subtype was compared with that of muscarine. Moreover, affinity and relative efficacy were calculated in vitro for this compound at M2 (heart force and rate) and M3 (ileum and bladder) receptors in order to investigate muscarinic receptor heterogeneity. The 4-deoxy-4-fluoromuscarines display a similar trend of potency as the corresponding muscarines and compound 1a shows differences in the affinity constants among the studied tissues. Replacement of a hydroxyl group for a fluorine atom in the 4 position of muscarine produces 1 order of magnitude increase in affinity for cardiac M2 muscarinic receptors controlling rate, while the affinity at cardiac M2 muscarinic receptors controlling force is unchanged, opening the possibility of a further classification of cardiac muscarinic receptors.

  DOI：

  10.1021/jm00095a003
• 作为产物：
  描述：

  (4S)-4-fluoro-5-oxo-6-<(S)-(4-methylphenyl)sulfinyl>hex-1-ene 在 二异丁基氢化铝 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 0.5h， 以96%的产率得到(4S,5R)-4-fluoro-5-hydroxy-6-<(S)-(4-methylphenyl)sulfinyl>hex-1-ene
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of enantiomerically pure 4-deoxy-4-fluoromuscarines

  摘要：

  Four isomers of [(4-fluoro-5-methyl-tetrahydrofuran-2-yl)methyl]trimethylammonium iodide (4-deoxy-4-fluoro-muscarines) were prepared in enantiomerically and diastereomerically pure form from (S)-(-)-methyl 4-methylphenyl sulfoxide, ethyl fluoroacetate, and allyl bromide. Their absolute configurations were assigned by H-1 NMR analyses. The four optically pure compounds were tested in vitro on guinea pig and their muscarinic potency was evaluated at M3 (ileum and bladder) and M2 (heart) muscarinic receptor subtypes. Compound 1a, the most potent isomer of the series, was also tested in vivo on pithed rat and its muscarinic activity at the M1 receptor subtype was compared with that of muscarine. Moreover, affinity and relative efficacy were calculated in vitro for this compound at M2 (heart force and rate) and M3 (ileum and bladder) receptors in order to investigate muscarinic receptor heterogeneity. The 4-deoxy-4-fluoromuscarines display a similar trend of potency as the corresponding muscarines and compound 1a shows differences in the affinity constants among the studied tissues. Replacement of a hydroxyl group for a fluorine atom in the 4 position of muscarine produces 1 order of magnitude increase in affinity for cardiac M2 muscarinic receptors controlling rate, while the affinity at cardiac M2 muscarinic receptors controlling force is unchanged, opening the possibility of a further classification of cardiac muscarinic receptors.

  DOI：

  10.1021/jm00095a003

文献信息

• Fluorinated analogues of nojirimycin and mannojirimycin from a non-carbohydrate precursor
  作者：Alberto Arnone、Pierfrancesco Bravo、Alessandro Donadelli、Giuseppe Resnati

  DOI：10.1016/0040-4020(95)00859-7

  日期：1996.1

  1,3,5-Trideoxy-3-fluoronojirimycin 3a and its 5-epi isomer 3b have been synthesized in enantiomerically pure form starting from the fluorohydroxysulfinylhexene (2R,3S,SS)-6. The nitrogen atom of the target bioactive compounds is introduced by replacing the sulfinyl group with an hydroxylamine residue and an intramolecular aminomercuration reaction builds up the desired piperidine ring. Finally, an

  从氟羟基亚磺酰基己烯（2 R，3 S，S S）-6开始，以对映体纯的形式合成了1,3,5-三甲氧基-3-氟诺奇霉素3a及其5-表位异构体3b。通过用羟胺残基取代亚磺酰基来引入目标生物活性化合物的氮原子，并且分子内氨基汞化反应会建立所需的哌啶环。最后，氧化脱汞得到羟甲基部分。相同的合成顺序可得到1,3,5-苯三氧基-3-氟甘露糖霉素4a及其5-表位异构体4b从苄氧基-氟亚磺酰基己烯（2 S，3 S，R S）-7起始。
• Asymmetric synthesis of fluorinated analogues of 1-deoxynojirimycin
  作者：Alberto Arnone、Pierfrancesco Bravo、Alessandro Donadelli、Giuseppe Resnati

  DOI：10.1039/c39930000984

  日期：——

  Two epimeric 1,3,4-trideoxy-3-fluoronojirimycins are obtained through a total asymmetric synthesis starting from a non-carbohydrate precursor; two key-steps of the synthetic sequence are an intramolecular aminomercuration reaction and an oxidative demercuration process.

  从非碳水化合物前体开始，通过全不对称合成获得了两种 1,3,4-三脱氧-3-氟尻酰亚胺嗪；合成序列的两个关键步骤是分子内氨酰胺化反应和氧化脱氨化过程。