1,5-dideoxy-1,5-(methyliminiumyl)-D-mannitol | 96627-33-7

• 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: 1,5-dideoxy-1,5-(methyliminiumyl)-D-mannitol
• 英文别名: N-methyl-deoxymannojirimycin；3,4,5-Piperidinetriol, 2-(hydroxymethyl)-1-methyl-, (2R-(2alpha,3bbeta,4alpha,5alpha))-；(2R,3R,4R,5R)-2-(hydroxymethyl)-1-methylpiperidine-3,4,5-triol
• CAS: 96627-33-7
• 化学式: C₇H₁₅NO₄
• 分子量: 177.2
• InChiKey: AAKDPDFZMNYDLR-DBRKOABJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  84.2
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  聚合甲醛 、 1-脱氧甘露伊霉素 在 甲酸 作用下， 反应 3.0h， 生成 1,5-dideoxy-1,5-(methyliminiumyl)-D-mannitol
  参考文献：
  名称：

  N-Alkylated Nitrogen-in-the-Ring Sugars: Conformational Basis of Inhibition of Glycosidases and HIV-1 Replication

  摘要：

  The conformations of nitrogen-in-the-ring sugars and their N-alkyl derivatives were studied from H-1 NMR analyses, mainly using (3)J(H,H) coupling constants and quantitative NOE experiments. No significant difference was seen in the ring conformation of 1-deoxynojirimycin (1), N-methyl-1-doexynojirimycin (2), and N-butyl-1-deoxynojirimycin (3). However, it was shown that the C6 OH group in 1 is predominantly equatorial to the piperidine ring, while that in 2 or 3 is predominantly axial, and its N-alkyl group is oriented equatorially. In the furanose analogues 1,4-dideoxy-1,4-imino-D-arabinitol (4) and its N-methyl (5) and N-butyl (6) derivatives, the five-membered ring conformation differed significantly by the presence or absence of the N-substituted group and the length of the N-alkyl chain. Compound 3 reduced its inhibitory effect on almost all glycosidases, resulting in an extremely specific inhibitor for processing alpha-glucosidase I since N-alkylation of 1 is known to enhance both the potency and specificity of this enzyme in vitro and in vivo. This preferred (C6 OH axial) conformation in 2 and 3 appears to be responsible for their strong alpha-glucosidase I activity. Compound 4 is a good inhibitor of intestinal alpha-glucohydrolases, alpha-glucosidase II, and Golgi alpha-mannosidases I and II, but its N-alkyl derivatives 5 and 6 markedly decreased inhibitory potential for all enzymes tested. In the case of 2,5-dideoxy-2,5-imino-D-mannitol (DMDP, 7), which is a potent beta-galactosidase inhibitor, its N-methyl (8) and N-butyl (9) derivatives completely lost potency toward beta-galactosidase as well. N-Alkylation of compounds 4 and 7, known well as potent yeast alpha-glucosidase inhibitors, resulted in a serious lass of inhibitory activity toward yeast alpha-glucohydrolases. Activity of these nine sugar analogues against HIV-1 replication was determined, based on the inhibition of virus-induced cytopathogenicity in MT-4 and MOLT-4 cells. Compounds 2 and 3, which are better inhibitors of alpha-glucosidase I than 1, proved active with EC(50) values of 69 and 49 mu g/mL in MT-4 cells and 100 and 37 mu g/mL in MOLT-4 cells, respectively, while none of the furanose analogues exhibited any inhibitory effects on HIV-1. The change in potency and specificity of bioactivity by N-alkylation of nitrogen-in-the-ring sugars appears to be correlated with their conformational change.

  DOI：

  10.1021/jm00013a012

文献信息

• ——
  作者：KINAST G.

  DOI：——

  日期：——