(+/-)-cis-1-Benzyl-3-(hydroxymethyl)piperidin-4-ol

• 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: (+/-)-cis-1-Benzyl-3-(hydroxymethyl)piperidin-4-ol
• 英文别名: rac-cis-1-benzyl-3-(hydroxymethyl)piperidin-4-ol；cis-1-benzyl-3-hydroxymethyl-4-piperidinol；1-benzyl-4-hydroxypiperidine-3-methanol；(3R,4R)-1-benzyl-3-(hydroxymethyl)piperidin-4-ol
• 化学式: C₁₃H₁₉NO₂
• 分子量: 221.299
• InChiKey: BLKKQITUZVROHP-CHWSQXEVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  43.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+/-)-cis-1-Benzyl-3-(hydroxymethyl)piperidin-4-ol 在 三乙胺 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 以68%的产率得到(1RS,3RS,6RS)-8-benzyl-3-chloro-2,4-dioxa-8-aza-3-phosphabicyclo[4.4.0]decane 3-oxide
  参考文献：
  名称：

  2,4-Dioxa-7-aza-，2,4-Dioxa-8-aza-和2,4-Dioxa-9-aza-3-phosphadecalins作为刚性乙酰胆碱模拟物：合成与表征

  摘要：

  合适的哌啶前体的磷酸化产生了一系列新型十氢化萘型O，N，P-杂环。标题化合物为P（3）轴向和P（3）赤道X取代，顺式和反式构型的2,4-dioxa-7-aza-，2,4-dioxa-8-aza-和2,4-二氧杂-9-氮杂-3-磷酸双环[4.4.0]癸烷3-氧化物（X = Cl，F，4-硝基苯氧基和2,4-二硝基苯氧基）被构型固定且构象受限的P-类似物乙酰胆碱的“甲氧基” ，因此代表乙酰胆碱（7-氮杂和9-氮杂异构体）或γ-均-乙酰胆碱模拟物（8-氮杂异构体）。作为乙酰胆碱酯酶（AChE）的不可逆抑制剂，这些化合物被认为是研究31抑制作用的立体化学过程的合适探针。P-NMR光谱。此外，这些模拟物的设计将使人们能够研究与AChE的分子相互作用，特别是乙酰胆碱的识别构象。

  DOI：

  10.1002/hlca.200490236
• 作为产物：
  描述：

  1-苄基-3-(羟基甲基)哌啶-4-醇 在 盐酸 、 水 、 对甲苯磺酸 作用下， 以 乙醇 、 正己烷 、 二氯甲烷 为溶剂， 生成 (+/-)-cis-1-Benzyl-3-(hydroxymethyl)piperidin-4-ol
  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

• Aza-C-nucleosides as a New Class of Nucleosides
  作者：Mads D. Sørensen

  DOI：10.1055/s-1999-3609

  日期：1999.11
• Iminosugars: potential inhibitors of liver glycogen phosphorylase
  作者：Palle Jakobsen、Jane M Lundbeck、Marit Kristiansen、Jens Breinholt、Helle Demuth、Jan Pawlas、Maria P Torres Candela、Birgitte Andersen、Niels Westergaard、Karsten Lundgren、Naoki Asano

  DOI：10.1016/s0968-0896(00)00291-1

  日期：2001.3

  The first synthesis of the single isomers (3R,4R,5R); (3S,4S,5S); (3R,4R,5S) and (3S,4S,5R) of 5-hydroxymethyl-piperidine-3,4-diol from Arecolin is reported, including the synthesis of a series of N-substituted derivatives of the (3R,4R,5R)-isomer (Isofagomine). The inhibitory effect of these isomers as well as of a series of N-substituted derivatives of the (3R,4R,SR)-isomer and selected hydroxypiperidine analogues on liver glycogen phosphorylase (GP) showed that the (3R,4R,5R) configuration was essential for obtaining an inhibitory effect at submicromolar concentration. The results also showed that all three hydroxy groups should be present and could not be substituted, nor were extra OH groups allowed if sub-micromolar inhibition should be obtained. Some inhibitory effect was retained for N-substituted derivatives of Isofagagomine; however, N-substitution always resulted in a loss of activity compared to the parent compound, IC50 values ranging from 1 to 100 muM were obtained for simple alkyl, arylalkyl and benzoylmethyl substituents. Furthermore, we found that it was not enough to assure inhibitory effect to have the (R,,R) configuration. Fagomine, the (2R,3R,4R)-2-hydroxymethylpiperidine-3,4-diol analogue, showed an IC50 value of 200 muM compared to 0.7 muM for Isofagomine. In addition, Isofagomine was able to prevent basal and glucagon stimulated glycogen degradation in cultured hepatocytes with IC50 values of 2-3 muM. (C) 2001 Elsevier Science Ltd. All rights reserved.
• 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.