acyclovir β-glucoside

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: acyclovir β-glucoside
• 英文别名: 2-amino-9-[2-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyethoxymethyl]-1H-purin-6-one
• 化学式: C₁₄H₂₁N₅O₈
• 分子量: 387.349
• InChiKey: OCDBZQIMUACCFE-ODYQSLDMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.5
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  194
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  阿昔洛韦 、 Cellobiose 在 cellulase 作用下， 以 acetate buffer 、 二甲基亚砜 为溶剂， 反应 3.0h， 以75%的产率得到acyclovir β-glucoside
  参考文献：
  名称：

  摘要：

  Purpose. To characterize the intestinal absorption of a beta-glucose conjugate of acyclovir (9-[(2-hydroxyethoxy) methyl] guanine, ACV) and compare it to ACV and its analogues in terms of stability and transport by Na+/glucose cotransporter (SGLT1).Methods. ACV beta glc was enzymatically synthesized using cellulase. Intestinal absorption experiments were performed with rat everted small intestine. Conformation of the glucose moiety was analyzed by NMR spectroscopy.Results. The ACV beta glc was stable on the mucosal side, and was transported to the serosal side in all regions of the small intestine. However, significant contribution of SGLT1 to the transport of ACV beta glc was not observed. NMR spectroscopic analysis indicated that the glucose conformation of ACV beta glc was the C-4(1) chair form, identical to beta-glucose or SGLT1-transportable beta-glucosides reported previously. Therefore, other factors such as molecular size and charge due to aglycone may cause no transport of ACV beta glc by SGLT1. On the other hand, the hydrophilicity of ACV beta glc was much higher than of ACV, suggesting water solubility-derived improvement of intestinal absorption of ACV.Conclusions. ACV beta glc is stable and absorbable, but it is not transported by SGLT1. No involvement of SGLT1 in the ACV beta glc transport is not due to glucose conformation.

  DOI：

  10.1023/a:1018818728393

文献信息

• ——
  作者：Takashi Mizuma、Satoshi Masubuchi、Shoji Awazu

  DOI：10.1023/a:1012103123580

  日期：——
• ——
  作者：Takashi Mizuma、Satoshi Masubuchi、Shoji Awazu

  DOI：10.1023/a:1018818728393

  日期：——

  Purpose. To characterize the intestinal absorption of a beta-glucose conjugate of acyclovir (9-[(2-hydroxyethoxy) methyl] guanine, ACV) and compare it to ACV and its analogues in terms of stability and transport by Na+/glucose cotransporter (SGLT1).Methods. ACV beta glc was enzymatically synthesized using cellulase. Intestinal absorption experiments were performed with rat everted small intestine. Conformation of the glucose moiety was analyzed by NMR spectroscopy.Results. The ACV beta glc was stable on the mucosal side, and was transported to the serosal side in all regions of the small intestine. However, significant contribution of SGLT1 to the transport of ACV beta glc was not observed. NMR spectroscopic analysis indicated that the glucose conformation of ACV beta glc was the C-4(1) chair form, identical to beta-glucose or SGLT1-transportable beta-glucosides reported previously. Therefore, other factors such as molecular size and charge due to aglycone may cause no transport of ACV beta glc by SGLT1. On the other hand, the hydrophilicity of ACV beta glc was much higher than of ACV, suggesting water solubility-derived improvement of intestinal absorption of ACV.Conclusions. ACV beta glc is stable and absorbable, but it is not transported by SGLT1. No involvement of SGLT1 in the ACV beta glc transport is not due to glucose conformation.