Dookhun Veedeeta, Bennet Andrew J
Department of Chemistry, Simon Fraser University, Burnaby, B.C., Canada.
J Am Chem Soc. 2005 May 25;127(20):7458-65. doi: 10.1021/ja042280e.
A reagent panel comprised of seven aryl beta-D-N-acetylneuraminides was synthesized and then used to probe the mechanisms of nonenzymatic hydrolysis. These reactions proceeded via four independent pathways: (1) acid-catalyzed hydrolysis of the neutral molecule; (2) acid-catalyzed hydrolysis of the anionic form, or its kinetic equivalent spontaneous hydrolysis of the neutral form; (3) spontaneous hydrolysis of the anionic form; and (4) a base-promoted pathway. The pH-independent spontaneous hydrolysis of 4-nitrophenyl alpha-D-N-acetylneuraminide (5) occurs at a rate that is over 100 times faster than that of the corresponding reaction of 4-nitrophenyl beta-D-N-acetylneuraminide (4a). Spontaneous hydrolyses of four aryl beta-D-N-acetylneuraminides displayed a beta(lg) value of -1.24 +/- 0.16 (pH = 8.1, T = 100 degrees C), and at a pH value of 1.0 (50 degrees C), all seven panel members gave a beta(lg) value of 0.14 +/- 0.08. The aqueous ethanolyses of 4a and 5 gave similar products and displayed sensitivity parameters (m) in a standard Winstein-Grunwald analysis of -0.04 +/- 0.01 and +0.23 +/- 0.02, respectively. These results, plus the activation parameters calculated for the spontaneous hydrolyses of the anionic forms of 5 (DeltaH() = 116 +/- 2 kJ mol(-1) and DeltaS = 27 +/- 4 J mol(-1) K(-1)) and 4a (DeltaH = 138 +/- 3 kJ mol(-1) and DeltaS = 59 +/- 8 J mol(-1) K(-1)), are inconsistent with anomeric carboxylate assistance occurring during the hydrolysis reactions, and the likely cause for the enhanced reactivity of 5 in comparison to that of 4a is an increase in ground-state steric strain.
合成了一个由七种芳基β-D-N-乙酰神经氨酸苷组成的试剂组，然后用于探究非酶促水解的机制。这些反应通过四条独立的途径进行：（1）中性分子的酸催化水解；（2）阴离子形式的酸催化水解，或其动力学等效的中性形式的自发水解；（3）阴离子形式的自发水解；以及（4）碱促进途径。4-硝基苯基α-D-N-乙酰神经氨酸苷（5）的与pH无关的自发水解速率比4-硝基苯基β-D-N-乙酰神经氨酸苷（4a）的相应反应速率快100多倍。四种芳基β-D-N-乙酰神经氨酸苷的自发水解显示β(lg)值为-1.24±0.16（pH = 8.1，T = 100℃），并且在pH值为1.0（50℃）时，所有七种试剂组成员的β(lg)值为0.14±0.08。4a和5的乙醇水溶液产生了相似的产物，并且在标准的温斯坦-格伦瓦尔德分析中的灵敏度参数（m）分别为-0.04±0.01和+0.23±0.02。这些结果，加上为5（ΔH() = 116±2 kJ mol(-1)和ΔS = 27±4 J mol(-1) K(-1)）和4a（ΔH = 138±3 kJ mol(-1)和ΔS = 59±8 J mol(-1) K(-1)）的阴离子形式的自发水解计算出的活化参数，与水解反应过程中异头羧酸盐的协助作用不一致，并且与4a相比5反应活性增强的可能原因是基态空间应变的增加。
