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Several motifs have been designed to mask the negative charges on the phosphorus moiety of either nucleoside monophosphates or nucleoside phosphonates, in order to increase their hydrophobicity and allow entry of the compound into the cell. Among them the bis\u2010amidate analogs, having two identical amino acids as masking groups through a P\u2013N bond, represent a more recent approach for the delivery of nucleotide analogs, endowed with antiviral or anticancer activity. Different synthetic strategies are commonly used for preparing phosphorodiamidates of nucleosides. In this protocol, we would like to focus on the description of the synthetic methodology that in our hand gave the best results using 2\u2032\u20103\u2032\u2010didehydro\u20102\u2032\u20103\u2032\u2010dideoxythymidine (d4T, Stavudine) as model nucleoside. A second strategy for preparing diamidates of nucleoside phosphonates will be reported using {[2\u2010(6\u2010amino\u20109 H\u2010purin\u20109\u2010yl)ethoxy]methyl}phosphonic acid (PMEA, adefovir) as model substrate. \u00a9 2015 by John Wiley &amp; Sons, Inc.<\/jats:p>","DOI":"10.1002\/0471142700.nc1506s60","type":"journal-article","created":{"date-parts":[[2015,3,9]],"date-time":"2015-03-09T13:52:26Z","timestamp":1425909146000},"source":"Crossref","is-referenced-by-count":3,"title":["Symmetrical Diamidate Prodrugs of Nucleotide Analogues for Drug Delivery"],"prefix":"10.1002","volume":"60","author":[{"given":"Fabrizio","family":"Pertusati","sequence":"first","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue  Cardiff CF10 3XF United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"McGuigan","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical 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