2,3,4,6-tetra-O-benzyl-D-gluconhydroximo-1,5-lactam | 153996-66-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2,3,4,6-tetra-O-benzyl-D-gluconhydroximo-1,5-lactam
• 英文别名: N-[(2R,3R,4S,5S)-3,4,5-tris(phenylmethoxy)-2-(phenylmethoxymethyl)-2,3,4,5-tetrahydropyridin-6-yl]hydroxylamine
• CAS: 153996-66-8
• 化学式: C₃₄H₃₆N₂O₅
• 分子量: 552.67
• InChiKey: HHTHHCFTOMAFFQ-NXVJRICRSA-N

物化性质

• 沸点：
  687.2±65.0 °C(predicted)
• 密度：
  1.17±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.72
• 重原子数：
  41.0
• 可旋转键数：
  13.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  81.54
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2,3,4,6-tetra-O-benzyl-D-gluconhydroximo-1,5-lactam 在 氨 、 sodium 作用下， 以 四氢呋喃 为溶剂， 生成 D-gluconhydroximo-1,5-lactam
  参考文献：
  名称：

  D-Gluconhydroximo-1,5-内酰胺及相关的N-芳基氨基甲酸酯理论计算，结构，合成及对β-葡萄糖苷酶的抑制作用

  摘要：

  已知的D-葡萄糖基氢肟1,5-内酰胺（= D-glucono-1,5-内酰胺肟）7a，其氮异构体7b和7c和N-芳基氨基甲酸酯26-29由2,3,4合成， 6-四-O-苄基-D-葡萄糖基1，5-内酰胺（11a）及其氮同位素异构体11b建立有争议的7a结构，并研究N-芳基氨基甲酸酯26-29对β-葡萄糖苷酶的抑制作用。用Lawesson试剂将11a转化为硫代内酰胺15a及其甘露糖醛的混合物-构型异构体16a，其转化为苄基化羟基内酰胺13a和甘露异构体17a的混合物。该混合物的脱苄基作用（Na / NH 3）和乙酰化作用导致生成了葡萄糖构型的五乙酸酯14a和甘露糖异构体18a。用Et 3 O·BF 4处理11a，然后用H 2 NOH处理，仅得到苄基化的D-葡萄糖基氢肟基-1,5-内酰胺（苄基化的D-去甲基内酰胺肟）13a，将其转化为14a。的脱乙酰图14a产生异羟肟酸内酰胺7a。通过类似的反应序列，使用15

  DOI：

  10.1002/hlca.19930760723
• 作为产物：
  描述：

  2,3,4,6-tetra-O-benzyl-D-glucono-δ-thiolactam 在 盐酸羟胺 、 碳酸氢钠 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以83%的产率得到2,3,4,6-tetra-O-benzyl-D-gluconhydroximo-1,5-lactam
  参考文献：
  名称：

  Synthesis and biological evaluation of d-gluconhydroximo-1,5-lactam and its oxime-substituted derivatives as pharmacological chaperones for the treatment of Gaucher disease

  摘要：

  38是一种高效的药理伴侣，适用于GCase相关的N370S细胞系，可以在12.5 μM时将突变蛋白的活性有效地提高1.93倍。

  DOI：

  10.1039/c5md00501a

文献信息

• Inhibition of Glycosidases by Lactam Oximes: Influence of the Aglycon in Disaccharide Analogues
  作者：Stefan Vonhoff、Tom D. Heightman、Andrea Vasella

  DOI：10.1002/(sici)1522-2675(19980909)81:9<1710::aid-hlca1710>3.0.co;2-i

  日期：1998.9.9
• Inhibition of Cellobiohydrolases fromTrichoderma reesei. Synthesis and Evaluation of Some Glucose-, Cellobiose-, and Cellotriose-Derived Hydroximolactams andImidazoles
  作者：Stefan Vonhoff、Kathleen Piens、Muriel Pipelier、Christophe Braet、Marc Claeyssens、Andrea Vasella

  DOI：10.1002/(sici)1522-2675(19990707)82:7<963::aid-hlca963>3.0.co;2-v

  日期：1999.7.7

  The lactam 16, the hydroximolactams 8, 20, 23, and 27, and the imidazole 32 were prepared following known methods. They were tested together with the known tetrazole 35 and the hydroximolactams 2 and 36 as inhibitors of the cellobiohydrolases Cel7A and Cel6A from Trichoderma reesei. Cel7A is only weakly inhibited by these compounds. Comparing their inhibitory activity evidences the importance of occupying subsites tl and +2. We results strongly suggest that the shape of none of the variants of the lactone-type inhibitor motif embodied by these inhibitors is complementary to the subsite - 1, i.e.,analogous to the transition state. Cel6A is rather strongly inhibited by the cellobiose analogues 20, 23, and 32, and by the cellotriose analogue 27. Their relative inhibitory activities evidence that binding at subsite -2 depends upon the shape of the moiety occupying subsite - 1. There is only a small difference between the inhibition by the hydroximolactams 20 and 23, which may be (partially) protonated by the catalytic acid of either anti- or syn-protonating glycosidases, and the imidazole 32, which can only be protonated by anti-protonating glycosidases. The results strongly suggest that shape requirements must be met by glycosidase inhibitors before they can be used to characterize the proton trajectory of glycosidases.