Howard Hughes Medical Institute and Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, United States.
J Am Chem Soc. 2010 Nov 24;132(46):16677-88. doi: 10.1021/ja108197s. Epub 2010 Nov 2.
The recent development of a sequential, high-yielding route to activated pyrimidine nucleotides, under conditions thought to be prebiotic, is an encouraging step toward the greater goal of a plausible prebiotic pathway to RNA and the potential for an RNA world. However, this synthesis has led to a disparity in the methodology available for stepwise construction of the canonical pyrimidine and purine nucleotides. To address this problem, and further explore prebiotically accessible chemical systems, we have developed a high-yielding, aqueous, one-pot, multicomponent reaction that tethers masked-sugar moieties to prebiotically plausible purine precursors. A pH-dependent three-component reaction system has been discovered that utilizes key nucleotide synthons 2-aminooxazole and 5-aminoimidazoles, which allows the first divergent purine/pyrimidine synthesis to be proposed. Due to regiospecific aminoimidazole tethering, the pathway allows N9 purination only, thus suggesting the first prebiotically plausible mechanism for regiospecific N9 purination.
在被认为是前生物条件下，最近开发出了一种连续高产的途径来合成活化的嘧啶核苷酸，这是朝着更大的目标——即合理的前生物途径合成 RNA 以及 RNA 世界的可能性——迈出的令人鼓舞的一步。然而，这种合成导致了用于逐步构建规范嘧啶和嘌呤核苷酸的方法之间存在差异。为了解决这个问题，并进一步探索前生物可及的化学系统，我们开发了一种高产、水相、一锅多组分反应，将掩蔽糖部分连接到前生物上似的嘌呤前体上。已经发现了一种依赖 pH 的三组分反应体系，它利用关键的核苷酸合成子 2-氨基恶唑和 5-氨基咪唑，这使得第一个发散的嘌呤/嘧啶合成被提出来。由于区域特异性的氨基咪唑连接，该途径只允许 N9 嘌呤化，因此提出了第一个区域特异性 N9 嘌呤化的前生物似的机制。
