2,3,4,6-tetra-O-acetyl-5-amino-5-deoxy-D-glucono-1,5-lactam | 134735-73-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2,3,4,6-tetra-O-acetyl-5-amino-5-deoxy-D-glucono-1,5-lactam
• 英文别名: [(2R,3R,4S,5R)-3,4,5-triacetyloxy-6-oxopiperidin-2-yl]methyl acetate
• CAS: 134735-73-2
• 化学式: C₁₄H₁₉NO₉
• 分子量: 345.306
• InChiKey: HGXJIUMQCYWRDL-FVCCEPFGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  134
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2,3,4,6-tetra-O-acetyl-5-amino-5-deoxy-D-glucono-1,5-lactam 在 盐酸 、 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 生成 1-脱氧野尻霉素
  参考文献：
  名称：

  由β-D-糖苷合成双脱氧和三脱氧亚氨基醛醇的一般方法。

  摘要：

  氨基糖（也称为氮杂糖）是一类重要的糖苷酶抑制剂，具有作为药物的巨大潜力，其中一类化合物的1，5-二甲氧基和1，5，6-三甲氧基亚氨基醛糖醇是其中的一员。它们的潜在治疗应用范围从糖尿病到癌症和艾滋病。我们在这里提出了一种从β-D-糖苷开始制备具有D-葡萄糖和D-半乳糖构型的化合物的一般方法。该方法特别具有吸引力，因为它具有很高的立体选择性和直接性。关键步骤是将糖苷选择性氧化为己磺酸，并将肟衍生物还原为内酰胺，然后将其进一步还原为目标化合物。如果C-6位带有乙酰氧基，则可以在还原过程中将其脱氧。然后产生三脱氧亚氨基糖。肟还原前的脱乙酰基产生双脱氧化合物。

  DOI：

  10.1016/s0008-6215(00)00124-5
• 作为产物：
  描述：

  野尻霉素 在 吡啶 、 sodium hydroxide 、 碘 作用下， 反应 24.0h， 生成 2,3,4,6-tetra-O-acetyl-5-amino-5-deoxy-D-glucono-1,5-lactam
  参考文献：
  名称：

  Enzyme-catalyzed aldol condensation for asymmetric synthesis of azasugars: synthesis, evaluation, and modeling of glycosidase inhibitors

  摘要：

  A combined fructose 1,6-diphosphate aldolase reaction and catalytic reductive amination has been used in the asymmetric synthesis of azasugars structurally corresponding to N-acetylglucosamine, N-acetylmannosamine, and deoxyhexoses. The 6-deoxyazasugars were prepared by direct hydrogenolysis of the aldolase product without removal of the 6-phosphate group. Both (R)- and (S)-3-azido-2-acetamidopropanal used as substrates in the aldolase reactions were prepared from the corresponding lipase-resolved 2-hydroxy species followed by formation of an aziridine intermediate and opening of the aziridine with azide. Evaluation of these azasugars and their diastereomerically pure tertiary amine oxides as well as 5-thioglucose and its sulfoxide derivatives as glycosidase inhibitors was carried out. It was found that all synthetic azasugars and 5-thioglucose were strong inhibitors, but oxidation of the ring heteroatom weakened the inhibition. With the aid of molecular modeling and inhibition analysis, a structure-K(i) relation of inhibitors was established which provides useful information for the design of new glycosidase inhibitors.

  DOI：

  10.1021/ja00016a039

文献信息

• d-Glyconhydroximolactams strongly inhibit α-glycosidases
  作者：Roland Hoos、Andrea Vasella、Karen Rupitz、Stephen G. Withers

  DOI：10.1016/s0008-6215(96)00320-5

  日期：1997.3

  It has been postulated that proton transfer to beta-glycosides by some retaining beta-glycosidases takes place in the plane of the pyranoside ring. It is now hypothesised that a similarly oriented catalytically active acidic group in alpha-glycosidases could interact with glyconolactone derivatives, provided that these are sufficiently basic to overcome the effect of a less favourable geometry by an energetically more favourable interaction. In keeping with this hypothesis, D-gluconolactone, D-gluconolactam, the tetrazole 3, and the hydroximolactone 5 are weak inhibitors of yeast alpha-glucosidase, while the hydroximolactam 6 (pK(a) = 4.8) is a mixed-type (alpha=2) strong inhibitor (K-i = 2.9 mu M). A Similar inhibition is observed for the arylcarbamoyl derivative 9, while the (methylthio)methyl derivative 10 inhibits more weakly and in a purely competitive fashion. The mannonhydroximolactam 11 strongly inhibits jack bean a-mannosidase (K-i=0.15 mu M), while the gluco analogue 6 inhibits about 80 times more weakly, illustrating the dependence upon configuration. (C) 1997 Elsevier Science Ltd.