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Facile Solid‐Phase Synthesis of AICAR 5′‐Monophosphate (ZMP) and Its 4‐ N ‐Alkyl Derivatives
Author(s) -
Oliviero Giorgia,
D'Errico Stefano,
Borbone Nicola,
Amato Jussara,
Piccialli Vincenzo,
Piccialli Gennaro,
Mayol Luciano
Publication year - 2010
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200901271
Subject(s) - chemistry , alkyl , moiety , carboxamide , nucleotide , imidazole , inosine monophosphate , purine , solid phase synthesis , inosine , combinatorial chemistry , amino acid , phosphate , stereochemistry , organic chemistry , biochemistry , enzyme , peptide , gene
We report herein a facile, solid‐phase synthesis of 5‐amino‐1‐β‐ D ‐ribofuranosylimidazole‐4‐carboxamide‐5′‐monophosphate (ZMP), a biosynthetic precursor of purine nucleotides, as well as a small collection of its 4‐ N ‐alkyl derivatives. The very difficult, direct, chemical phosphorylation of 5‐amino‐1‐β‐ D ‐ribofuranosylimidazole‐4‐carboxamide (AICAR) was circumvented by installing a suitable, fully protected, phosphate group on the 5′‐position of N ‐1‐(2,4‐dinitrophenyl)inosine, connected to the solid support through the 2′,3′‐positions, prior to the purine degradation, which led to the 5‐amino‐imidazole‐4‐carboxamide moiety. A plausible reaction mechanism for the formation of the ZMP imidazole was also reported.