Towards a Total Synthesis of Aminoacylated t-RNAs

In the ribosomal biosynthesis of proteins, the aminoacylated t-RNAs serve as carriers of the amino acids. A total synthesis of these biological key-compounds would allow the site-specific incorporation of modifications within the t-RNA and attachment of any desired amino acid. Such analogues are useful tools for structural and functional studies, and for the incorporation of unnatural amino acids into proteins.

Our retrosynthetic scheme for the preparation of aminoacylated t-RNAs includes the synthesis of truncated t-RNAs, the synthesis of aminoacylated RNA-fragments, and their subsequent ligation. In this article, we present our approaches toward the realization of these three tasks.