Abstract The diversity of backbone modifications in the study of primitive informational polymers is partly limited by the plausible formation of their prebiotic starting components. In this paper, we synthesize pyrazine nucleic acid, an acyclic polymer, with the nucleoside derivable from a prebiotic one-pot synthesis containing alanine amide and D-ribose. Pyrazine nucleic acid (PzNA) which has a backbone structurally similar to glycerol nucleic acid (GNA), contain pyrazine derived nucleosides as informational elements that may exhibit base pairing properties similar to the pyrimidines present in RNA.[1] We found that insertion of pyrazinone nucleotides into DNA oligonucleotide sequences is not well-tolerated, and that homogenous sequences of PzNA are unable to form duplexes with RNA or DNA. Reasons for our results may be attributed to the pyrazine-2-one moiety, which is purposed to be a thymine analog, but has a lower pKa (pKa ∼ 8.5) than thymine and uracil. Additionally, we discovered an “apparent” regioselective protection of pyrazine-2-one derivatives in the presence of a secondary hydroxyl group that proved crucial in the preparation of the pyrazine-2-one phosphoramidite. The regioselectivity observed is proposed to be of general interest in the context of heterocyclic chemistry. In the larger context of origins of life studies, it points to the importance of keto-enol preferences of the canonical nucleobases versus pyrazine heterocycles in functioning as recognition elements.

中文翻译：

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吡嗪核酸的合成及碱基配对特性

摘要 原始信息聚合物研究中骨架修饰的多样性部分受到其益生元起始成分的合理形成的限制。在本文中，我们合成了吡嗪核酸，一种无环聚合物，其核苷来源于益生元一锅合成，含有丙氨酸酰胺和 D-核糖。吡嗪核酸 (PzNA) 的骨架结构与甘油核酸 (GNA) 相似，含有吡嗪衍生的核苷作为信息元件，可能表现出与 RNA 中存在的嘧啶相似的碱基配对特性。 [1] 我们发现将吡嗪酮核苷酸插入 DNA 寡核苷酸序列的耐受性不佳，并且 PzNA 的同源序列无法与 RNA 或 DNA 形成双链体。我们的结果的原因可能归因于 pyrazine-2-one 部分，该部分旨在成为胸腺嘧啶类似物，但其 pKa（pKa ∼ 8.5）低于胸腺嘧啶和尿嘧啶。此外，我们发现了在仲羟基存在下对 pyrazine-2-one 衍生物的“明显”区域选择性保护，这在 pyrazine-2-one 亚磷酰胺的制备中至关重要。观察到的区域选择性被认为在杂环化学的背景下受到普遍关注。在生命起源研究的更大背景下，它指出了规范核碱基与吡嗪杂环的酮烯醇偏好在作为识别元件的作用中的重要性。我们发现了 pyrazine-2-one 衍生物在仲羟基存在下的“明显”区域选择性保护，这在 pyrazine-2-one 亚磷酰胺的制备中被证明是至关重要的。观察到的区域选择性被认为在杂环化学的背景下受到普遍关注。在生命起源研究的更大背景下，它指出了规范核碱基与吡嗪杂环的酮烯醇偏好在作为识别元件的作用中的重要性。我们发现了 pyrazine-2-one 衍生物在仲羟基存在下的“明显”区域选择性保护，这在 pyrazine-2-one 亚磷酰胺的制备中被证明是至关重要的。观察到的区域选择性被认为在杂环化学的背景下受到普遍关注。在生命起源研究的更大背景下，它指出了规范核碱基与吡嗪杂环的酮烯醇偏好在作为识别元件的作用中的重要性。