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Synthesis of a Cyclic Dinucleotide Analogue with Ambiguous Bases, 5-Aminoimidazole-4-carboxamide
Noriko S Tarashima1, Yusuke Kumanomido1, Katsuyuki Nakashima2
1Graduate School of Pharmaceutical Science, Tokushima University, Shomachi 1-78-1, Tokushima 770-8505, Japan.
Abstract:
Cyclic dinucleotides (CDNs) are second messengers composed of two purine nucleotides. In recent years, the structural diversity of CDNs and their functionality in biological processes are being intensely studied. Herein we report the chemical synthesis of cyclic di-5-aminoimidazole-4-carboxamide-1-β-d-ribofuranosyl monophosphate (c-di-ZMP) (1), which consists of two 5-amino-4-imidazolecarboxamide ribonucleotides (Z-ribonucleotides) linked via two phosphodiester linkages. Construction of the CDN skeleton with an N1-dinitrophenylhypoxanthine base (HxaDNP-base) by phosphoramidite chemistry and the subsequent ring-opening reaction of HxaDNP-base successfully yielded the desired 1.
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