(3R,4R,5R)-1-allyl-5-hydroxymethyl-3,4-piperidinediol

• 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: (3R,4R,5R)-1-allyl-5-hydroxymethyl-3,4-piperidinediol
• 英文别名: (3R,4R,5R)-5-(hydroxymethyl)-1-prop-2-enylpiperidine-3,4-diol
• 化学式: C₉H₁₇NO₃
• 分子量: 187.239
• InChiKey: BJBIKSIUSBGNDA-IWSPIJDZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  63.9
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  槟榔碱 在 氢氧化钾 、 锂硼氢 、 1-氯乙基氯甲酸酯 、 三乙基硼氢化锂 、 三乙胺 、 间氯过氧苯甲酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 甲苯 为溶剂， 反应 7.58h， 生成 (3R,4R,5R)-1-allyl-5-hydroxymethyl-3,4-piperidinediol
  参考文献：
  名称：

  Iminosugars: potential inhibitors of liver glycogen phosphorylase

  摘要：

  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.

  DOI：

  10.1016/s0968-0896(00)00291-1

文献信息

• NOVEL HETEROCYCLIC COMPOUNDS
  申请人：NOVO NORDISK A/S

  公开号：EP0983239A1

  公开（公告）日：2000-03-08
• US6046214A
  申请人：——

  公开号：US6046214A

  公开（公告）日：2000-04-04
• [EN] NOVEL HETEROCYCLIC COMPOUNDS<br/>[FR] NOUVEAUX COMPOSES HETEROCYCLIQUES
  申请人：NOVO NORDISK A/S

  公开号：WO1998050359A1

  公开（公告）日：1998-11-12

  (EN) Novel piperidine compounds are provided, and those compounds are useful in the treatment and/or prevention of diabetes, and especially non-insulin dependent diabetes (NIDDM or type 2 diabetes) including overnight or meal treatment and treatment or prevention of long-term complications, such as retinopathy, neuropathy, nephropathy, and micro- and macro-angiopathy; treatment of hyperglycemia, hypercholesterolemia, hypertension, hyperinsulinemia, hyperlipidemia, atherosclerosis or myocardial ischemia.(FR) L'invention concerne de nouveaux composés de pipéridine. Ces composés permettent de traiter et/ou de prévenir le diabète, et en particulier, le diabète non insulino-dépendant (NIDDM ou diabète de type 2). Ils sont également utiles dans le traitement de nuit ou au cours des repas, et le traitement ou la prévention de complications à long terme, comme la rétinopathie, la neuropathie, la néphropathie, et la micro- et macro-angiopathie, le traitement de l'hyperglycémie, l'hypercholestérolémie, l'hypertension, l'hyperinsulinémie, l'hyperlipidémie, l'athérosclérose ou l'ischémie myocardique.
• 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.