Lysidine is a modified nucleoside found in bacterial tRNA and is nearly universally conserved. The biosynthesis of lysidine occurs post-transcriptionally from tRNA at cytidine 34, the first position of the anticodon. This single modification changes not only the amino acid attached to the tRNA (from methionine to isoleucine) but also its codon recognition from 5'-AUG to 5'-AUA. Herein we describe an efficient route for the synthesis of lysidine from cytidine consisting of six steps with overall yields >50% and only one chromatographic step. The key amine addition step utilizes LiCl and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to ensure clean conversion to a single tautomeric product. This route has been used to prepare lysidine in quantities suitable for structural characterization and incorporation into RNA oligomers. Current studies are focused on measuring the base pairing specificity of the lysidine incorporated anticodon as well as the structural elucidation of base paired lysidine using NMR spectroscopy.

Efficient total synthesis of lysidine and progress towards the structural characterization of lysidine base pairing in RNA

245th National Meeting (2013)

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