(R)-N-tert-butoxycarbonylpiperidin-3-ylmethyl acetate | 831169-55-2

• 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: (R)-N-tert-butoxycarbonylpiperidin-3-ylmethyl acetate
• 英文别名: 1,1-Dimethylethyl (3R)-3-[(acetyloxy)methyl]-1-piperidinecarboxylate；tert-butyl (3R)-3-(acetyloxymethyl)piperidine-1-carboxylate
• CAS: 831169-55-2
• 化学式: C₁₃H₂₃NO₄
• 分子量: 257.33
• InChiKey: DSKBLSVOGMOGAH-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  55.84
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (R)-N-tert-butoxycarbonylpiperidin-3-ylmethyl acetate 在 盐酸 、 sodium tris(acetoxy)borohydride 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 3.0h， 生成 (R)-N-ethylpiperidin-3-ylmethyl acetate
  参考文献：
  名称：

  N-[¹⁸F]Fluoroethylpiperidin-4ylmethyl Acetate, a Novel Lipophilic Acetylcholine Analogue for PET Measurement of Brain Acetylcholinesterase Activity

  摘要：

  The reduction of acetylcholinesterase (AChE) activity in the brain has been measured in dementia disorders such as Alzheimer's disease and dementia with Lewy bodies using C-11-labeled acetylcholine analogues, N-[C-11]methylpiperidin-4-yl acetate and propionate, and positron emission tomography (PET). Our aim was to develop an F-18-labeled acetylcholine analogue useful for brain AChE mapping with PET, since F-18, with a longer half-life, has advantages over C-11. In a preliminary study, a series of N-[C-14]ethylpiperidin-3-yl or -4yl-methanol esters (acetyl and propionyl esters) were newly designed and evaluated in vitro regarding the reactivity with and specificity to AChE using purified human enzymes, leading to a novel F-18-labeled acetylcholine analogue, N-[F-18]fluoroethylpiperidin-4-ylmethyl acetate. In rat experiments, the F-18-labeled candidate showed desirable properties for PET AChE measurement: high brain uptake of the authentic ester, high AChE specificity, a moderate hydrolysis rate, and low membrane permeability (metabolic trapping) of the metabolite.

  DOI：

  10.1021/jm049100w
• 作为产物：
  描述：

  (R)-1-Boc-3-羟甲基哌啶 、 乙酰氯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 (R)-N-tert-butoxycarbonylpiperidin-3-ylmethyl acetate
  参考文献：
  名称：

  N-[¹⁸F]Fluoroethylpiperidin-4ylmethyl Acetate, a Novel Lipophilic Acetylcholine Analogue for PET Measurement of Brain Acetylcholinesterase Activity

  摘要：

  The reduction of acetylcholinesterase (AChE) activity in the brain has been measured in dementia disorders such as Alzheimer's disease and dementia with Lewy bodies using C-11-labeled acetylcholine analogues, N-[C-11]methylpiperidin-4-yl acetate and propionate, and positron emission tomography (PET). Our aim was to develop an F-18-labeled acetylcholine analogue useful for brain AChE mapping with PET, since F-18, with a longer half-life, has advantages over C-11. In a preliminary study, a series of N-[C-14]ethylpiperidin-3-yl or -4yl-methanol esters (acetyl and propionyl esters) were newly designed and evaluated in vitro regarding the reactivity with and specificity to AChE using purified human enzymes, leading to a novel F-18-labeled acetylcholine analogue, N-[F-18]fluoroethylpiperidin-4-ylmethyl acetate. In rat experiments, the F-18-labeled candidate showed desirable properties for PET AChE measurement: high brain uptake of the authentic ester, high AChE specificity, a moderate hydrolysis rate, and low membrane permeability (metabolic trapping) of the metabolite.

  DOI：

  10.1021/jm049100w

文献信息

• Chemical and Enzymatic Resolution of (<i>R,S</i>)-<i>N</i>-(<i>tert</i>-Butoxycarbonyl)-3-hydroxymethylpiperidine
  作者：Animesh Goswami、Jeffrey M. Howell、Edward Y. Hua、K. David Mirfakhrae、Maxime C. Soumeillant、Shankar Swaminathan、Xinhua Qian、Fernando A. Quiroz、Truc C. Vu、Xuebao Wang、Bin Zheng、David R. Kronenthal、Ramesh N. Patel

  DOI：10.1021/op010210b

  日期：2001.7.1

  (S)-N-(tert-Butoxycarbonyl)-3-hydroxymethylpiperidine 1 was made from (R,S)-3-hydroxymethylpiperidine 2 via fractional crystallization of the corresponding L(-)-dibenzoyl tartarate salt 3 followed by hydrolysis and acylation. Lipase from Pseudomonas cepacia was found to be the best enzyme for the stereospecific resolution of (RS)-N-(tert-butoxycarbonyl)-3-hydroxymethylpiperidine 4. (S)-N-(tert-Butoxycarbonyl)-3-hydroxymethylpiperidine I was obtained in 16% yield and >95% enantiomeric excess (ee) by hydrolysis of (R,S)-acetate 5 by lipase PS from Pseudomonas cepacia. Lipase PS-catalyzed esterification of the (RS)-N-(tert-butoxycarbonyl)-3-hydroxymethylpiperidine 4 with succinic anhydride provided the S-hemisuccinate ester 6, which could be easily separated and hydrolyzed by base to the (S)-N-(tert-butoxycarbonyl)-3-hydroxymethylpiperidine 1. The yield and ee could be improved greatly by repetition of the process. Using the repeated esterification procedure(S)-N-(tert-butoxycarbonyl)-3-hydroxymethylpiperidine I was obtained in 32% yield (maximum theoretical yield 50%) and 98.9% ee.