Reversible Hydrolysis Reaction with the Spore Photoproduct under Alkaline Conditions
Reversible Hydrolysis Reaction with the Spore Photoproduct under Alkaline Conditions
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碱性条件下孢子光产物的可逆水解反应
DOI：
10.1021/acs.joc.6b01846
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Li, Lei
中科院分区：
文献类型：
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作者：
Adhikari, Surya;Lin, Gengjie;Li, Lei
DNA损伤可能会降低核碱基处的电子密度，使它们在碱处理后易于进一步修饰。在紫外线照射的细菌内生孢子中发现的主要DNA光损伤是胸腺嘧啶二聚体，5-胸腺嘧啶基-5，6-二氢胸腺嘧啶，即，孢子光产物（SP）。在这里，我们报告了一个逐步添加/消除反应中的SP水解产物在强碱性条件下，其中脲基基团被添加到羧基部分，形成一个环酰胺，再生SP后消除氢氧根离子。在催化剂存在下通过与胺反应的羧酸的直接酰胺化是有据可查的;然而，在没有活化的情况下发生酰胺化反应是非常罕见的。在水溶液中的这种未催化的SP逆反应甚至更令人惊讶，因为羧基部分由于其携带的负电荷而不是良好的亲电体。对另外两个饱和嘧啶损伤，5，6-二氢-2 ′-脱氧尿苷和嘧啶（6-4）嘧啶酮光产物的碱催化水解的研究表明，即使所有三个水解反应可能共享相同的二醇中间体，也没有一个反应是可逆的。因此，其中两个胸腺嘧啶残基保持堆叠构象的SP结构可能提供了所需的框架，使得这种非常不寻常的羧基加成/消除反应成为可能。
DNA lesions may reduce the electron density at the nucleobases, making them prone to further modifications upon the alkaline treatment. The dominant DNA photolesion found in UV-irradiated bacterial endospores is a thymine dimer, 5-thyminyl-5,6-dihydrothymine, i.e., the spore photoproduct (SP). Here we report a stepwise addition/elimination reaction in the SP hydrolysis product under strong basic conditions where a ureido group is added to the carboxyl moiety to form a cyclic amide, regenerating SP after eliminating a hydroxide ion. Direct amidation of carboxylic acids by reaction with amines in the presence of a catalyst is well documented; however, it is very rare for an amidation reaction to occur without activation. This uncatalyzed SP reverse reaction in aqueous solution is even more surprising because the carboxyl moiety is not a good electrophile due to the negative charge it carries. Examination of the base-catalyzed hydrolyses of two other saturated pyrimidine lesions, 5,6-dihydro-2′-deoxyuridine and pyrimidine (6–4) pyrimidone photoproduct, reveals that neither reaction is reversible even though all three hydrolysis reactions may share the samegem-diol intermediate. Therefore, the SP structure where the two thymine residues maintain a stacked conformation likely provides the needed framework enabling this highly unusual carboxyl addition/elimination reaction.