chlorophostin | 1014977-30-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: chlorophostin
• 英文别名: 2-amino-6-chloro-9-{3'-O-(α-D-glucopyranosyl)-β-D-ribofuranosyl}purine 2',3'',4''-trisphosphate；[(2R,3R,4R,5R)-2-(2-amino-6-chloropurin-9-yl)-4-[(2R,3R,4R,5R,6R)-3-hydroxy-6-(hydroxymethyl)-4,5-diphosphonooxyoxan-2-yl]oxy-5-(hydroxymethyl)oxolan-3-yl] dihydrogen phosphate
• CAS: 1014977-30-0
• 化学式: C₁₆H₂₅ClN₅O₁₈P₃
• 分子量: 703.771
• InChiKey: ZCTMXBGAFPNZIV-UQFRLDGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.9
• 重原子数：
  43
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  358
• 氢给体数：
  10
• 氢受体数：
  22

反应信息

• 作为产物：
  描述：

  2-amino-6-chloro-9-{5'-O-benzyl-2'-O-(dibenzyloxyphosphoryl)-3'-O-[2'',6''-di-O-benzyl-3'',4''-bis-(dibenzyloxyphosphoryl)-α-D-glucopyranosyl]-β-D-ribofuranosyl}purine 在 三氯化硼 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以74%的产率得到chlorophostin
  参考文献：
  名称：

  2-Position Base-Modified Analogues of Adenophostin A as High-Affinity Agonists of the d-myo-Inositol Trisphosphate Receptor:  In Vitro Evaluation and Molecular Modeling

  摘要：

  [Graphics]Adenophostin A (AdA) is a potent agonist of the D-myo-inositol 1,4,5-trispliosphate receptor (ins(1,4,5)P3R). Various 2-aminopurine analogues of AdA were synthesized, all of which (guanophostin 5, 2,6-diaminopurinophostin 6, 2-aminopurinophostin 7, and chlorophostin 8) are more potent than 2-methoxy-N-6-methyl AdA, the only benchmark of this class. The 2-amino-6-chloropurine nucleoside 11, from Vorbruggen condensation of 2-amino-6-chloropurine with appropriately protected. disaccharide, served as the advanced common precursor for all the analogues. Alcoholysis provided the precursor for 5, ammonolysis at high temperature the precursor for 6, and ammonolysis under mild conditions the precursor for synthesis of 7 and 8. For 8, the debenzylation of precursor leaving the chlorine untouched was achieved by judicious use of BCl3. The reduced potency of chlorophostin 8 and higher potency of guanophostin 5 in assays of Call release via recombinant Ins(1,4,5)P3R are in agreement with our model suggesting a cation-pi interaction between AdA and Ins(1,4,5)P3R. The similar potencies of 2,6-diaminopurinophostin (6) and 2-aminopurinophostin (7) concur with previous reports that the 6-NH2 moiety contributes negligibly to the potency of AdA. Molecular modeling of the 2-amino derivatives suggests an interaction between the carboxylate side chain of Glu505 of the receptor and the 2-NH2 of the ligand, but for 2-methoxy-N-6-methyl AdA the carboxylate group of Glu505 is deflected away from the methoxy group. A helix-dipole interaction between the 1-phosphate of Ins(1,4,5)P-3 and the 2'-phosphate of AdA with alpha-helix 6 of Ins(1,4,5)P3R is postulated. The results support a proposed model for high-affinity binding of AdA to Ins(1,4,5)P3R.

  DOI：

  10.1021/jo702617c

文献信息

• 2-Position Base-Modified Analogues of Adenophostin A as High-Affinity Agonists of the <scp>d</scp>-<i>myo</i>-Inositol Trisphosphate Receptor:  In Vitro Evaluation and Molecular Modeling
  作者：Kana M. Sureshan、Melanie Trusselle、Stephen C. Tovey、Colin W. Taylor、Barry V. L. Potter

  DOI：10.1021/jo702617c

  日期：2008.3.1

  [Graphics]Adenophostin A (AdA) is a potent agonist of the D-myo-inositol 1,4,5-trispliosphate receptor (ins(1,4,5)P3R). Various 2-aminopurine analogues of AdA were synthesized, all of which (guanophostin 5, 2,6-diaminopurinophostin 6, 2-aminopurinophostin 7, and chlorophostin 8) are more potent than 2-methoxy-N-6-methyl AdA, the only benchmark of this class. The 2-amino-6-chloropurine nucleoside 11, from Vorbruggen condensation of 2-amino-6-chloropurine with appropriately protected. disaccharide, served as the advanced common precursor for all the analogues. Alcoholysis provided the precursor for 5, ammonolysis at high temperature the precursor for 6, and ammonolysis under mild conditions the precursor for synthesis of 7 and 8. For 8, the debenzylation of precursor leaving the chlorine untouched was achieved by judicious use of BCl3. The reduced potency of chlorophostin 8 and higher potency of guanophostin 5 in assays of Call release via recombinant Ins(1,4,5)P3R are in agreement with our model suggesting a cation-pi interaction between AdA and Ins(1,4,5)P3R. The similar potencies of 2,6-diaminopurinophostin (6) and 2-aminopurinophostin (7) concur with previous reports that the 6-NH2 moiety contributes negligibly to the potency of AdA. Molecular modeling of the 2-amino derivatives suggests an interaction between the carboxylate side chain of Glu505 of the receptor and the 2-NH2 of the ligand, but for 2-methoxy-N-6-methyl AdA the carboxylate group of Glu505 is deflected away from the methoxy group. A helix-dipole interaction between the 1-phosphate of Ins(1,4,5)P-3 and the 2'-phosphate of AdA with alpha-helix 6 of Ins(1,4,5)P3R is postulated. The results support a proposed model for high-affinity binding of AdA to Ins(1,4,5)P3R.