SOLVOLYSIS OF ADENINE NUCLEOSIDES .1. EFFECTS OF SUGARS AND ADENINE SUBSTITUENTS ON ACID SOLVOLYSES
SOLVOLYSIS OF ADENINE NUCLEOSIDES .1. EFFECTS OF SUGARS AND ADENINE SUBSTITUENTS ON ACID SOLVOLYSES
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DOI：
10.1021/ja00779a040
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发表时间：
1972-01-01
影响因子：
15
通讯作者：
MEHTA, PJ
中科院分区：
文献类型：
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作者：
GARRETT, ER;MEHTA, PJ
2‘C-甲基腺苷产生相应的糖和稳定的腺嘌呤部分，但1-甲基腺苷的情况除外，在1-甲基腺苷的情况下，生成的1-甲基腺嘌呤转化为5-氨基咪唑-4-YV’-甲基甲基酰胺的速度较慢。上面给出了0.10Mhc1中80个相对活动的典型排名。已经在不同的酸和缓冲液浓度以及不同的温度下对其中许多化合物进行了研究。观察到只有特定的酸催化质子化和非质子化物种的溶解率，并且在低pH区没有最大溶解率的事实支持了反对在醚氧攻击之后的希夫碱中间体的论点。二质子化腺嘌呤核苷与氮基上1位和7位上的质子发生溶剂化反应的可能性是由于活化熵5*接近于零这一事实。虽然2‘-羟基对腺苷糖基的诱导作用抑制了酸溶作用，但用氢取代3’-羟基可显著提高反应活性。取代基对腺嘌呤部分的嘧啶环的影响很小，而咪唑部分的C-8上的溴或甲氧基的取代则有更显著的影响，这与有助于质子化的诱导效应的适当顺序一致。这一点和其他证据与假设是一致的，即质子化的嘌呤核心氢离子攻击咪唑基团，很可能是在7位，而不是在醚氧上。事实上，1-甲基腺苷阳离子在酸中的溶解速度与腺苷阳离子的速度大致相同，这一事实强烈地表明，后者的1-质子化形式与第二个质子反应，产生溶解反应。基于较简单的糖基胺的类似溶解，提出了核苷在酸中溶解为碱和糖的机理解释。1基本步骤是糖环氧的质子化，糖环的打开，然后水攻击席夫碱，生成杂环碱和糖。2-4如果
2'C-methyladenosine result in the respective sugar and stable adenine moiety except in the case of 1-methyladenosine where the resultant 1-methyladenine is more slowly transformed into 5-aminoimidazole-4-yV'-methylcarboxamidine. The typical ranking of relative activities are given above for 80 in 0.10 Mhc1. Studies have been conducted at various acid and buffer concentrations, and at various temperatures for many of these compounds. The facts that only specific acid catalyzed solvolyses of the protonated and non-protonated species were observed and that there was no maximum in solvolysisrate in the low pH region supported the argument against a Schiff base intermediate subsequent to ethereal oxygenattack. The probability of an Al mechanism for solvolyses of diprotonated adenine nucleosides with protons on the nitrogens in the 1 and 7 positions is favored by the fact that the entropies of activation, 5*, are close to zero. Although the inductive effect of the 2'hydroxyl on the sugar moiety of adenosine inhibits acidsolvolysis, a less significant increase in reactivity is introduced by the substitution of a hydrogen for the 3'hydroxyl. The effects of substituents on the pyrimidine ring of theadenine moiety lead to onlyminor effects in reactivity whereas substitution of a bromine or methoxyl group on C-8 of the imidazoleportion has a more pronounced effect consistent with the appropriate order for in-ductive effects aiding protonation. This and otherevidence is consistent with the presumption that hydrogenion attack of the protonated purine nucleosideto form a solvolyzing dication by an Al mechanism is on the imidazole moiety andmost probably at the 7 position rather than on the ethereal oxygen. The fact that the 1-methyladenosine cation solvolyses in acid at about the same rate as the adenosine cation strongly suggests that it is the 1-protonated form of the latter that reacts with a second proton to result in a solvolyzing dication.Amechanistic explanation of the acid solvolysis of the nucleosides to a base and a sugar has been pro-posed based on the analogous solvolysis of the simpler glycosylamines. 1 The essential steps were considered to be the protonation of the sugar ring oxygen, sugar ring opening, followed by water attack on the Schiff base to yield the heterocyclic base and sugar. 2-4 If the