Lysidine (k²C) is one of the most modified pyrimidine RNA bases. It is a cytidine nucleoside, in which the 2‐oxo functionality of the heterocycle is replaced by the ϵ‐amino group of the amino acid lysine. As such, lysidine is an amino acid‐containing RNA nucleoside that combines directly genotype (C‐base) with phenotype (lysine amino acid). This makes the compound particularly important in the context of theories about the origin of life and here especially for theories that target the origin of translation. Here, we report the total synthesis of the U‐derivative of lysidine (k²U), which should have the same base pairing characteristics as k²C if it exists in the isoC‐like tautomeric form. To investigate this question, we developed a phosphoramidite building block for k²U, which allows its incorporation into RNA strands. Within RNA, k²U can base pair with the counter base U and isoG, confirming that k²U prefers an isoC‐like tautomeric structure that is also known to dominate for k²C. The successful synthesis of a k²U phosphoramidite and its use for RNA synthesis now paves the way for the preparation of a k²C phosphoramidite and RNA strands containing k²C.

中文翻译：

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k2U的合成和掺入RNA

赖氨酸（k ² C）是修饰最多的嘧啶RNA碱基之一。这是一个胞苷核苷，其中该杂环的2-氧代功能由取代ε氨基酸赖氨酸的ε-氨基。因此，赖氨酸是一种含氨基酸的RNA核苷，直接将基因型（C碱基）与表型（赖氨酸氨基酸）结合在一起。这使得复合词在关于生命起源的理论的背景下，尤其是在针对翻译起源的理论中，尤其重要。在这里，我们报告了赖氨酸的U衍生物（k ² U）的总合成，它应具有与k ²相同的碱基配对特征C（如果它以isoC类互变异构形式存在）。为了研究这个问题，我们开发了k ² U的亚磷酰胺构件，可将其掺入RNA链。在RNA中，k ² U可以与反碱基U和isoG碱基配对，从而证实k ² U更喜欢以isoC形式存在的互变异构结构，该结构也已知在k ² C中起主导作用。ak ² U亚磷酰胺及其衍生物的成功合成现在用于RNA合成的方法为ak ² C亚磷酰胺和含有k ² C的RNA链的制备铺平了道路。