201677-01-2Relevant academic research and scientific papers
Synthesis of {[5-(adenin-9-yl)-2-furyl]methoxy}methyl phosphonic acid and evaluations against human adenylate kinases
Kaci, Malika,Uttaro, Jean-Pierre,Lefort, Valerie,Mathe, Christophe,El Amri, Chahrazade,Perigaud, Christian
, p. 4227 - 4230 (2014)
AMP mimics constitute an important class of therapeutic derivatives to treat diseases where the pool of ATP is involved. A new phosphonate derivative of 9-(5-hydroxymethylfuran-2-yl)adenine was synthesized in a multi-step sequence from commercially available adenosine. Its ability to behave as a substrate of human adenylate kinases 1 and 2 was assessed. The phosphonate was shown to be a moderate but selective substrate of the mitochondrial human AK2, better than well-known antiviral acyclic phosphonates 9-(2-phosphonomethoxyethyl)adenine (PMEA, Adefovir) and (R)-9-(2-phosphonomethoxypropyl)adenine (PMPA, Tenofovir). Putative binding mode within adenylate kinase NMP site revealed by molecular docking in comparison to AMP native substrate allowed to illustrate this selective behavior.
Generation of C-1' radicals through a β-(acyloxy)alkyl rearrangement in modified purine and pyrimidine nucleosides
Gimisis, Thanasis,Ialongo, Giuseppina,Chatgilialoglu, Chryssostomos
, p. 573 - 592 (2007/10/03)
The synthesis of protected 1',2'-didehydro-2'-deoxyadenosines has been optimized by incorporating a phosphoranylidene protection of the adenine amine function. These unsaturated adenosines have served as substrates for the electrophilic iodopivaloyloxylation leading to new nucleosides modified at the anomeric position. Reaction of halopivaloates 10, 11 and 12 with tributyltin hydride generates indirectly C-1' radicals through a β- (acyloxy)alkyl rearrangement. Rate constants for these rearrangements have been measured by using free-radical clock methodology and comparison of these data with previous reported results provides structural information about the nature of this important class of radicals.
