benzyl 2,3-O-[(2R,3R)-2,3-dimethoxybutane-2,3-diyl]-6-O-p-toluenesulfonyl-βD-glucopyranoside | 1254190-36-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: benzyl 2,3-O-[(2R,3R)-2,3-dimethoxybutane-2,3-diyl]-6-O-p-toluenesulfonyl-βD-glucopyranoside
• CAS: 1254190-36-7
• 化学式: C₂₆H₃₄O₁₀S
• 分子量: 538.616
• InChiKey: UFGDPGKRBVQJFI-DOLRGSGLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.51
• 重原子数：
  37.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  118.98
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  benzyl 2,3-O-[(2R,3R)-2,3-dimethoxybutane-2,3-diyl]-6-O-p-toluenesulfonyl-βD-glucopyranoside 在 三氟乙酸 作用下， 反应 1.0h， 以95%的产率得到benzyl 4-O-methyl-6-O-p-toluenesulfonyl-β-D-glucopyranoside
  参考文献：
  名称：

  Probing the active-site requirements of human intestinal N-terminal maltase glucoamylase: The effect of replacing the sulfate moiety by a methyl ether in ponkoranol, a naturally occurring α-glucosidase inhibitor

  摘要：

  Ponkoranol is a naturally occurring glucosidase inhibitor isolated from the plant Salacia reticulata. The compound comprises a sulfonium ion with an internal sulfate counter ion. We report here an efficient synthetic route to 3'-O-methyl ponkoranol to test the hypothesis that occupation of a hydrophobic pocket by a methyl group instead of the polar sulfate ion within the active site of human N-terminal maltase glucoamylase would be beneficial. The synthetic strategy relies on the nucleophilic attack of 2,3,5-tri-O-benzyl-1,4-anhydro-4-thio-D-arabinitol at the C-6 position of benzyl 6-O-p-toluenesulfonyl beta-D-glucopyranoside, followed by deprotection using boron trichloride and reduction with sodium borohydride. The target compound inhibited the N-terminal catalytic domain of intestinal human maltase glucoamylase (ntMGAM) with a K-i value of 0.50 +/- 0.04 mu M, higher than those of de-O-sulfonated ponkoranol (K-i = 43 +/- 3 nM), or its 5'-stereoisomer (K-i = 15 +/- 1 nM). We conclude that the interaction of the methyl group with hydrophobic residues in the active site is not as beneficial to inhibition of ntMGAM as the other interactions of the polyhydroxylated chain with active-site residues. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.020
• 作为产物：
  描述：

  benzyl 2,3-O-[(2R,3R)-2,3-dimethoxybutane-2,3-diyl]-β-D-glucopyranoside 、 对甲苯磺酰氯 在 吡啶 作用下， 以75%的产率得到benzyl 2,3-O-[(2R,3R)-2,3-dimethoxybutane-2,3-diyl]-6-O-p-toluenesulfonyl-βD-glucopyranoside
  参考文献：
  名称：

  Probing the active-site requirements of human intestinal N-terminal maltase glucoamylase: The effect of replacing the sulfate moiety by a methyl ether in ponkoranol, a naturally occurring α-glucosidase inhibitor

  摘要：

  Ponkoranol is a naturally occurring glucosidase inhibitor isolated from the plant Salacia reticulata. The compound comprises a sulfonium ion with an internal sulfate counter ion. We report here an efficient synthetic route to 3'-O-methyl ponkoranol to test the hypothesis that occupation of a hydrophobic pocket by a methyl group instead of the polar sulfate ion within the active site of human N-terminal maltase glucoamylase would be beneficial. The synthetic strategy relies on the nucleophilic attack of 2,3,5-tri-O-benzyl-1,4-anhydro-4-thio-D-arabinitol at the C-6 position of benzyl 6-O-p-toluenesulfonyl beta-D-glucopyranoside, followed by deprotection using boron trichloride and reduction with sodium borohydride. The target compound inhibited the N-terminal catalytic domain of intestinal human maltase glucoamylase (ntMGAM) with a K-i value of 0.50 +/- 0.04 mu M, higher than those of de-O-sulfonated ponkoranol (K-i = 43 +/- 3 nM), or its 5'-stereoisomer (K-i = 15 +/- 1 nM). We conclude that the interaction of the methyl group with hydrophobic residues in the active site is not as beneficial to inhibition of ntMGAM as the other interactions of the polyhydroxylated chain with active-site residues. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.020