5'-O-levulinyl-2'-O-tetrahydropyranyl-2-N-(4-(t-butyl)benzoyl)-6-O-(2-nitrophenyl)guanosine-3'-triethylammonium(2-chlorophenyl)phosphate | 139391-19-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5'-O-levulinyl-2'-O-tetrahydropyranyl-2-N-(4-(t-butyl)benzoyl)-6-O-(2-nitrophenyl)guanosine-3'-triethylammonium(2-chlorophenyl)phosphate
• 英文别名: 5'-O-levulinyl-2'-O-tetrahydropyranyl-2-N-(t-butylbenzoyl)-6-O-(2-nitrophenyl)-guanosine-3'-triethylammonium (2-chlorophenyl)phosphate；5'-O-levulinyl-2'-O-tetrahydropyranyl-2-N-[4-(t-butyl)benzoyl]-6-O-(2-nitrophenyl)guanosine-3'-triethylammonium(2-chlorophenyl)phosphate
• CAS: 139391-19-8
• 化学式: C₆H₁₅N*C₄₃H₄₆ClN₆O₁₄P
• 分子量: 1038.49
• InChiKey: GBAJOXFCSPDCQU-VAWLZMJMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.36
• 重原子数：
  72.0
• 可旋转键数：
  20.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  255.13
• 氢给体数：
  2.0
• 氢受体数：
  18.0

反应信息

• 作为反应物：
  描述：

  5'-O-levulinyl-2'-O-tetrahydropyranyl-2-N-(4-(t-butyl)benzoyl)-6-O-(2-nitrophenyl)guanosine-3'-triethylammonium(2-chlorophenyl)phosphate 、 2'-O-tetrahydropyranyl-N-3-(4-toluoyl)-uridine 在 吡啶 、 N-甲基咪唑 、 2,4,6-三甲基苯磺酰氯 作用下， 反应 0.67h， 生成
  参考文献：
  名称：

  四聚体环状分支RNA（lariat）的合成，用于模拟II组的内含子和核mRNA前加工反应（剪接）

  摘要：

  据报道，环状分支四核糖核苷酸9的融合合成，模拟了前mRNA加工反应（剪接）的套索。本策略的第一步是将适当保护的5'-O-乙酰丙酰-G3'p5'U3'磷酸二酯嵌段4与3'，5'-二羟基-6-N-苯甲酰基-2'-缩合在活化剂的存在下，O-pixyl（9-苯基黄嘌呤-9-基）腺苷5得到6a（53％）。对6a的3'-OH进行化学特异性磷酸化，得到中间体6b（88％），将其用中酸进行处理，以实现区域特异性地去除2'-O-pixyl的基团，得到化合物6c（99％）。第二个关键步骤涉及在6c中将双氰基乙基磷酸三酯部分引入到支点腺苷的2'-OH中，在一个步骤中使用（双氰基乙氧基）-（二异丙基氨基）膦生成关键的支点结构单元6d（68 ％），与2'-两个不同的连位磷酸盐和3'-的分支点，6D然后用缩合N-4-苯甲酰基-2'，3'-二-O-乙酰基胞苷然后专门从除去7a中通过水合肼得到中间体7b（83％），随后用

  DOI：

  10.1016/s0040-4020(01)91031-2

文献信息

• Solution conformation of hexameric & heptameric lariat-RNAs and their self-cleavage reactions which give products mimicking those from some catalytic RNAs (ribozymes)
  作者：B. Rousse、N. Puri、G. Viswanadham、P. Agback、C. Glemarec、A. Sandström、C. Sund、J. Chattopadhyaya

  DOI：10.1016/s0040-4020(01)80852-8

  日期：1994.1

  The small ''lariat'' hexameric 1 and heptameric 2 RNAs undergo self-cleavage, whereas the two cyclic A(2'-->5)G and A(3'-->5')G linked tetramers 3 and 4 do not self-cleave. The site of phosphodiester cleavage is specific and occurs at the 3'-phosphate of the guanosine residue to give a guanosine 2',3'-cyclic phosphate and a 5'-hydroxyl termini. At 22 degrees C, the heptamer 2 (k = 0.16 x 10(-3) min(-1)) cleaves ca. six times faster than the hexamer 1 (k = 0.25 x 10(-4) min(-1)). The rare of cleavage is temperature and pH dependent. The addition of Mg2+ ions slightly increases the rate of cleavage, but NMR studies show that it does not produce any changes in the conformation of the ribose rings and of the glycosidic bonds. H-1-NMR shows that the lariat-hexamer 1 exists as two conformers (A and B) in slow exchange on the NMR time scale. The enthalpy term (Delta H = 7.1 kcal mol(-1)) favours the A-form while the entropy term (Delta S = 21 cal mol(-1) K-1) favours the B-form. The energy of activation for the transition between the A- and B-forms is 23 kcal.mol(-1). The loop nucleotides in the B-form of hexamer 1 have ribose, glycosidic bonds and phosphate backbone conformation that are very similar to those of heptamer 2. At low temperature, the conformation of the A(2'-->5)G linked tetramer 3 and A(3'-->5')G linked tetramer 4 is very similar to the conformation of the A-form of hexamer 1. Torsional constraints derived from H-1-H-1, H-1-P-31 and C-13-P-31 coupling constants were used for molecular dynamics simulations in water with sodium counterions for a total of 226 ps. The MD simulations were first carried out with torsional constraints derived from J-couplings (0-96 ps) and then completely without constraints (106-226 ps). No major conformational changes occurred upon the release of the constraints indicating that the ensemble of conformers generated during the MD simulation are not artificially held in these conformations by the NMR constraints and these conformers may be good representatives of the actual NMR observed solution structures. A comparison of the self-cleavage rate between hexamer, heptamer and hammerhead-RNA (k(cat) approximate to 0.5 min(-1) at 37 degrees C) also suggests that the cleavage-site geometry of the hammerhead-RNA should be much closer to the transition state/intermediate geometry than heptamer 2. The pH-dependent study of the self-cleavage reaction of hexamer hexamer 1 has shown that the self-cleavage rate peaks at pH 6 and slows down considerably both above and below this pH. Nonspecific cleavage starts becoming important at a very low pH (less than or equal to 3) and at a high pH (greater than or equal to 10). The structures generated during both NMR constrained and unconstrained MD runs show that the cleavage-site between G(3) and U-7 in heptamer 2 has the following average local conformation: S-sugar for G(3), epsilon(-) (-86 degrees+/-13 degrees), zeta(+) (91 degrees+/-16 degrees),alpha(+) (85 degrees+/-24 degrees), beta(t) (163 degrees+/-13 degrees) and gamma(+) (65 degrees+/-11 degrees). Molecular modelling studies on the MD generated geometry show that a simple rotation of the local phosphate backbone at the cleavage-site from epsilon(-) (d(O2'-3'P) = 3.8 Angstrom) --> epsilon = 120 degrees (d(O2'-3'P) = 2.8 Angstrom) and a rotation of zeta(+) --> zeta(t) would position the leaving 5'-terminus of U-7 for a potential in-line displacement by 2'-OH of G(3) (Note that in the latter geometrical transition, alpha(+), beta(t) and gamma(+) and the South-sugar of U-7 remain unchanged). Such a geometry at the cleavage site would produce an optimal local structure for a neighbouring nucleophilic attack by 2'-OH to give the trigonal-bipyramidal phosphorane transition state/intermediate.