AI Article Synopsis
- A new method for creating phosphoramidate prodrugs of -nucleosides has been developed using various phosphorochloridates and specific derivatives of deoxypseudoisocytidine.
- The reaction also shows unique side reactions, such as epimerization, highlighting the distinct behavior of -nucleosides compared to other nucleoside analogues.
- Preliminary findings suggest that these prodrugs can be activated enzymatically by carboxypeptidase, similar to conventional nucleoside prodrugs, indicating potential for further research in anti-cancer therapies.
Article Abstract
A synthetic procedure for the preparation of phosphoramidate prodrugs of -nucleosides is reported. Different phosphorochloridates were reacted with 3'--protected -acetyl-2'-deoxypseudoisocytidine or 3'--protected 2'-deoxypseudoisocytidine, followed by acidic hydrolysis of the protecting group. In the presence of the -acetyl moiety, the enolisable keto group of the nucleobase was able to react (like the 5'-OH) with the phosphorochloridates to give bisphosphorylated derivatives. Epimerisation (β to α) occurred if the amino group of the nucleobase was unprotected. These side reactions demonstrate the peculiar behaviour of -nucleosides compared to their nucleoside analogues. It was demonstrated that the first enzymatic activation step for this new class of prodrugs can be mediated by carboxypeptidase and that it follows the same pathway and rate reported for ProTides of more conventional nucleoside analogues. These new phosphoramidate derivatives deserve further investigation for their therapeutic potential as anti-cancer agents.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474688 | PMC |
| http://dx.doi.org/10.1002/open.201700019 | DOI Listing |
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