guanophostin A | 897364-72-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: guanophostin A
• 英文别名: [(2R,3R,4R,5R)-2-(2-amino-6-oxo-1H-purin-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: 897364-72-6
• 化学式: C₁₆H₂₆N₅O₁₉P₃
• 分子量: 685.326
• InChiKey: KBLOYWFOUMWGLC-UQFRLDGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -8.7
• 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：
  374
• 氢给体数：
  11
• 氢受体数：
  20

反应信息

• 作为产物：
  描述：

  2-amino-6-O-benzyl-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 palladium dihydroxide 甲醇 、 环己烯 作用下， 以 水 为溶剂， 以100%的产率得到guanophostin A
  参考文献：
  名称：

  Guanophostin A: Synthesis and evaluation of a high affinity agonist of the d-myo-inositol 1,4,5-trisphosphate receptor

  摘要：

  Guanophostin A 是 1,4,5-三磷酸肌醇受体激动剂腺苷 A 的鸟苷对应物，已被合成，它是第一个在刺激细胞内 Ca2+ 释放方面与其母体等效的合成腺苷 A 类似物；据推测，其核苷酸分子通过鸟嘌呤基阳离子-π堆叠与 Arg504、氢键与 Glu505 以及核糖基 2′-磷酸基团与 α6 的螺旋偶极相互作用，与受体结合核心相互作用。

  DOI：

  10.1039/b517911d

文献信息

• Guanophostin A: Synthesis and evaluation of a high affinity agonist of the d-myo-inositol 1,4,5-trisphosphate receptor
  作者：Kana M. Sureshan、Melanie Trusselle、Stephen C. Tovey、Colin W. Taylor、Barry V. L. Potter

  DOI：10.1039/b517911d

  日期：——

  Guanophostin A, the guanosine counterpart of the inositol 1,4,5-trisphosphate receptor agonist adenophostin A, has been synthesized and is the first synthetic adenophostin A-like analogue to be equipotent to its parent in stimulating intracellular Ca2+ release; its nucleotide moiety is proposed to interact with the receptor binding core by guanine base cation-π stacking with Arg504 and hydrogen bonding with Glu505 and interaction of the ribosyl 2′-phosphate group with the helix-dipole of α6.

  Guanophostin A 是 1,4,5-三磷酸肌醇受体激动剂腺苷 A 的鸟苷对应物，已被合成，它是第一个在刺激细胞内 Ca2+ 释放方面与其母体等效的合成腺苷 A 类似物；据推测，其核苷酸分子通过鸟嘌呤基阳离子-π堆叠与 Arg504、氢键与 Glu505 以及核糖基 2′-磷酸基团与 α6 的螺旋偶极相互作用，与受体结合核心相互作用。
• 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.