Biolabile constructs for pronucleotide design

Separation of diastereoisomers of Ara-C phosphotriesters using solid phase extraction and HPLC for the study of their decomposition kinetic in cell extracts

“…Added concentration (mol L −1 ) photriester series of AZT [35][36][37][38], pronucleotide 2 should be bioconverted into its corresponding phenylphosphodiester derivative through an esterase-mediated activation mechanism (Fig. 2).…”

Aryl nucleoside H-phosphonates. Part 16: Synthesis and anti-HIV-1 activity of di-aryl nucleoside phosphotriesters

“…Typical examples include cyclic phosphate derivatives (e.g., nucleoside saligenyl phosphates, cyclo-Sal), 10 or nucleoside phosphoramidates. 11,12 Another class of pronucleotides is represented by pivaloyloxymethyl (POM 7 ), dithioethyl (DTE 13 ) and S-acyl-2-thioethyl (SATE [13][14][15] ) nucleoside phosphotriesters, whose bio-activation is triggered by enzymatic cleavage of a carboxylic acid ester group (POM and SATE), or a disulfide bond of the side chain (DTE), followed by a spontaneous intramolecular conversion into the corresponding nucleoside monophosphates. Synthesis and biological activity of these compounds were widely studied and were subjects of several reviews.…”

Separation of nucleoside phosphoramidate diastereoisomers by high performance liquid chromatography and capillary electrophoresis☆

“…In this area, we previously reported the potentialities of mononucleoside phosphiotriester derivatives of AZT (3 -azido-2 ,3 -dideoxythymidine) bearing one S-acyl-thioethyl (SATE) group and aryl residue as biolabile phosphate protections [7][8][9][10]. In cell culture experiments, such bioconstructs allow the efficient intracellular delivery of the parent 5 -mononucleotide.…”

“…To improve the oral bioavailability of these potential therapeutic agents, i.e. their intestinal absorption, a new series of compounds incorporating an amino acid residue was synthesized [10][11][12][13][14][15]. Permeation of these phosphoramidates across the intestinal mucosa could namely be increased by active transport [16].…”