4-O-benzyl-2-deoxy-2-C-hydroxymethyl-D-glucopyranose

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-O-benzyl-2-deoxy-2-C-hydroxymethyl-D-glucopyranose
• 英文别名: 4-O-Benzyl-2-desoxy-2-C-hydroxymethyl-D-glucose；(3R,4R,5S,6R)-3,6-bis(hydroxymethyl)-5-phenylmethoxyoxane-2,4-diol
• 化学式: C₁₄H₂₀O₆
• 分子量: 284.309
• InChiKey: NONQPVAUURCRFQ-GNMOMJPPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  99.4
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-O-benzyl-2-deoxy-2-C-hydroxymethyl-D-glucopyranose 在 sodium periodate 、 sodium cyanoborohydride 作用下， 以 甲醇 、 水 为溶剂， 反应 75.5h， 生成 (3R,4R,5R)-1-benzyl-3-(benzyloxy)-5-(hydroxymethyl)piperdin-4-ol
  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
• 作为产物：
  描述：

  1,6-anhydro-4-O-benzyl-2-deoxy-2-C-vinyl-β-D-glucopyranose 在 sodium tetrahydroborate 、 硫酸 、 臭氧 作用下， 反应 1.0h， 生成 4-O-benzyl-2-deoxy-2-C-hydroxymethyl-D-glucopyranose
  参考文献：
  名称：

  Jespersen, Tina M.; Dong, Wenling; Sierks, Michael R., Angewandte Chemie, 1994, vol. 106, # 17, p. 1858 - 1860

  摘要：

  DOI：

文献信息

• [EN] PIPERIDINES AND PYRROLIDINES<br/>[FR] PIPERIDINES ET PYRROLIDINES
  申请人：NOVO NORDISK A/S

  公开号：WO1995024391A1

  公开（公告）日：1995-09-14

  (EN) Compounds (I) and (II), the use of these compounds as medicament, the use of these medicaments in the treatment of diabetes and pharmaceutical compositions containing these compounds.(FR) Composés (I) et (II), leur utilisation comme médicaments, utilisation de ces médicaments pour le traitement du diabète et compositions pharmaceutiques renfermant ces composés.

  (EN) 化合物（I）和（II），这些化合物作为药物的使用，这些药物在糖尿病治疗中的使用以及含有这些化合物的制药组合物。 (FR) 化合物（I）和（II），这些化合物作为药物的使用，这些药物在糖尿病治疗中的使用以及含有这些化合物的制药组合物。
• Heterocyclic compounds
  申请人：Novo Nordisk A/S

  公开号：US06046214A1

  公开（公告）日：2000-04-04

  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 longterm complications, such as retinopathy, neuropathy, nephropathy, and micro- and macroangiopathy; treatment of hyperglycemia, hypercholesterolemia, hypertension, hyperinsulinemia, hyperlipidemia, atherosclerosis or myocardial ischemia.

  提供了新型哌啶化合物，这些化合物可用于治疗和/或预防糖尿病，特别是非胰岛素依赖性糖尿病（NIDDM或2型糖尿病），包括夜间或餐后治疗以及治疗或预防长期并发症，如视网膜病变、神经病变、肾病、微血管和宏血管病变；治疗高血糖、高胆固醇血症、高血压、高胰岛素血症、高脂血症、动脉粥样硬化或心肌缺血。
• Use of hydroxy alkyl piperidine and pyrrolidine compounds to treat
  申请人：Novo Nordisk A/S

  公开号：US05863903A1

  公开（公告）日：1999-01-26

  The present invention relates to hydroxy alkyl piperidine compounds and pharmaceutical compositions thereof which can be used to treat diabetes.

  本发明涉及羟基烷基哌啶化合物及其制备的制药组合物，可用于治疗糖尿病。
• Noeuromycin,¹ A Glycosyl Cation Mimic that Strongly Inhibits Glycosidases
  作者：Huizhen Liu、Xifu Liang、Helmer Søhoel、Anne Bülow、Mikael Bols

  DOI：10.1021/ja010240u

  日期：2001.5.1
• Synthesis and Chemistry of Noeuromycin and Isofagomine Analogues
  作者：Huizhen Liu、Vinni H. Lillelund、Jens Andersch、Xifu Liang、Mikael Bols

  DOI：10.1081/car-200030070

  日期：2004.12.29

  Several N-substituted analogues of noeuromycin ((2RS,3S,4R,5R)-2,3,4-trihydroxy-5 -hydroxymethylpiperidine) and isofagomine ((3R,4R,5R)-3,4-dihydroxy-5-hydroxymethylpiperidine) were synthesised. The isofagomine analogues (3RS,4RS,5RS)N-(2-phosphonoethyl)-3,4-dihydroxy-5-hydroxymethyl-piperidine, (3SR,4SR,5RS)-N-(2-phosphonoethyl)-3,4-dihydroxy-5-hydroxy-methylpiperidine, and (3R,4R,5R)-N-(10-chloro-9-anthracenemethyl)-3,4-dihydroxy-5-hydroxy-methylpiperidine were synthesised by direct alkylation of the corresponding azasugar. N-Substituted noeuromycin derivatives could not be made in this straightforward manner, but were made by modification of a synthesis intermediate. By this method (2RS,3S,4R,5R)-N-(4-methoxyphenyl)-2,3,4-trihydroxy-5-hydroxymethylpiperidine and (2RS,3S,4R,5R)-N-nonyl-2,3,4-trihydroxy-5-hydroxymethylpiperidine were synthesised. The stability of noeuromycin was studied and was found to depend on stereochemistry and pH. The L-fuco isomer ((2RS, 3R,4R,5R)-2,3,4-trihydroxy-5-methylpiperidine) was observed to undergo a particularly facile Amadori rearrangement at neutral pH to the 3-ketopiperidine. A noeuromycin analogue, that could not undergo the Amadori rearrangement, was synthesised.