{(3S,4R)-1-benzyl-4-[(2R)-3,3,3-trifluoro-2-methoxy-1-oxo-2-phenylpropoxy]piperidin-3-yl}methyl (αR)-α-methoxy-α-(trifluoromethyl)-benzeneacetate | 1135150-49-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: {(3S,4R)-1-benzyl-4-[(2R)-3,3,3-trifluoro-2-methoxy-1-oxo-2-phenylpropoxy]piperidin-3-yl}methyl (αR)-α-methoxy-α-(trifluoromethyl)-benzeneacetate
• 英文别名: [(3S,4R)-1-benzyl-4-[(2R)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoyl]oxypiperidin-3-yl]methyl (2R)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoate
• CAS: 1135150-49-0
• 化学式: C₃₃H₃₃F₆NO₆
• 分子量: 653.619
• InChiKey: WLMLLYLVIHTWAY-FKVXNAHKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  46
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  74.3
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  1-苄基-3-(羟基甲基)哌啶-4-醇 在 4-二甲氨基吡啶 、 对甲苯磺酸 、 三乙胺 作用下， 以 乙醇 、 正己烷 、 二氯甲烷 为溶剂， 生成 {(3S,4R)-1-benzyl-4-[(2R)-3,3,3-trifluoro-2-methoxy-1-oxo-2-phenylpropoxy]piperidin-3-yl}methyl (αR)-α-methoxy-α-(trifluoromethyl)-benzeneacetate
  参考文献：
  名称：

  合成和表征对映体纯的顺式和反式-3-氟-2,4-二恶英-8-氮杂-3-磷酸钙素3氧化物作为γ-高乙酰胆碱模拟物和乙酰胆碱酯酶抑制剂

  摘要：

  标题化合物为P（3）轴向和P（3）赤道取代的顺式和反式构型的8-苄基-3-氟-2,4-二氧杂-8-氮杂-3-磷酸钙素3-氧化物（ = 8-苄基-3-氟-2,4-二氧杂-8-氮杂-3-磷酸双环[4.4.0]癸烷3-氧化物= 2-氟六氢-6-（苯甲基）-4 H -1,3,2制备了-dioxaphosphorino [5,4 - c ]吡啶2-氧化物（ee> 98％）并进行了充分表征（方案2和3）。绝对构型由其前体对映体纯的顺式和反式确定明确分配的-1-苄基-4-羟基哌啶-3-甲醇。它们是构型固定且受构象约束的乙酰基γ-胆碱（= 3-（乙酰氧基）-N，N，N-三甲基丙烷-1-氨基）磷类似物，是研究与乙酰胆碱酯酶的分子相互作用的合适探针。通过动力学方法确定，所有化合物都是酶的弱抑制剂。

  DOI：

  10.1002/hlca.201100369

文献信息

• The Absolute Configuration of the (+)- and (−)-<i>cis</i>- and (+)- and (−)-<i>trans-</i>1-Benzyl-4-hydroxypiperidine-3-methanols: An Unusual Application of the¹H-NMR-<i>Mosher</i>Method
  作者：Christian Clerc、Igor Matarazzo、Peter Rüedi

  DOI：10.1002/hlca.200800270

  日期：2009.1

  Abstractmagnified imageThe enantiomerically pure title compounds were prepared and the absolute configurations assigned by the high‐field 1H‐NMR application of the Mosher method on the bis‐MTPA derivatives (MTPA=α‐methoxy‐α‐(trifluoromethyl)benzeneacetic acid). The final evidence for the adaptability of the procedure was effected by X‐ray crystallographic analyses. The absolute configurations of the cis‐ and trans‐1‐benzyl‐4‐hydroxypiperidine‐3‐methanols are as follows: (+)‐(3S,4S) and (−)‐(3R,4R) (cis), and (+)‐(3R,4S) and (−)‐(3S,4R) (trans), respectively (Scheme 2). Nonfermenting bakers' yeast reduction of methyl 1‐benzyl‐4‐oxopiperidine‐3‐carboxylate afforded (+)‐methyl (3R,4S)‐1‐benzyl‐4‐hydroxypiperidine‐3‐carboxylate (de>97%, ee>99%) which was further reduced to the (+)‐(3S,4S)‐diol (Scheme 3). The result confirms the stereochemical outcome of the biological reduction with re‐face selectivity and cis‐diastereoselectivity as predicted for bakers' yeast. The 4‐hydroxypiperidine‐3‐methanols are the key starting compounds for the synthesis of the enantiomerically pure P(3)‐axially and P(3)‐equatorially substituted cis‐ and trans‐configurated 8‐benzyl‐2,4‐dioxa‐8‐aza‐3‐phosphadecalin 3‐oxides (=8‐benzyl‐2,4‐dioxa‐8‐aza‐3‐phospha‐bicyclo[4.4.0]decane 3‐oxides) representing γ‐homo‐acetylcholine mimetics.
• Synthesis and Characterization of Enantiomerically Pure cis- and trans-3-Fluoro-2,4-dioxa-8-aza-3-phosphadecalin 3-Oxides as γ-Homoacetylcholine Mimetics and Inhibitors of Acetylcholinesterase
  作者：Christian Clerc、Peter Rüedi

  DOI：10.1002/hlca.201100369

  日期：2012.1

  and trans‐configured 8‐benzyl‐3‐fluoro‐2,4‐dioxa‐8‐aza‐3‐phosphadecalin 3‐oxides (=8‐benzyl‐3‐fluoro‐2,4‐dioxa‐8‐aza‐3‐phosphabicyclo[4.4.0]decane 3‐oxides=2‐fluorohexahydro‐6‐(phenylmethyl)‐4H‐1,3,2‐dioxaphosphorino[5,4‐c]pyridine 2‐oxides) were prepared (ee>98%) and fully characterized (Schemes 2 and 3). The absolute configurations were established from that of their precursors, the enantiomerically

  标题化合物为P（3）轴向和P（3）赤道取代的顺式和反式构型的8-苄基-3-氟-2,4-二氧杂-8-氮杂-3-磷酸钙素3-氧化物（ = 8-苄基-3-氟-2,4-二氧杂-8-氮杂-3-磷酸双环[4.4.0]癸烷3-氧化物= 2-氟六氢-6-（苯甲基）-4 H -1,3,2制备了-dioxaphosphorino [5,4 - c ]吡啶2-氧化物（ee> 98％）并进行了充分表征（方案2和3）。绝对构型由其前体对映体纯的顺式和反式确定明确分配的-1-苄基-4-羟基哌啶-3-甲醇。它们是构型固定且受构象约束的乙酰基γ-胆碱（= 3-（乙酰氧基）-N，N，N-三甲基丙烷-1-氨基）磷类似物，是研究与乙酰胆碱酯酶的分子相互作用的合适探针。通过动力学方法确定，所有化合物都是酶的弱抑制剂。