Structure of Cyclic Nucleoside Phosphonate Ester Prodrugs: An Inquiry

Abstract

The configuration at phosphorus in cyclic (S)-HPMPC (1, Cidofovir) and (S)-HPMPA (2) phenyl ester (5 and 6, respectively) diastereomers ((Rp)-5, (Rp)-6, (Sp)-6) were determined by X-ray crystallography and correlated to their 1H and 31P NMR spectra in solution. (Rp)-5 and (Rp)-6 have chair conformations with the nucleobase substituent equatorial and the P-OPh axial. Perhaps surprisingly, (Sp)-6 is (a, a) in the crystal and exists largely as an equilibrium of (a, a)/ (e, e) conformers in chloroform or acetonitrile.

Evolution of an Amino Acid Based Prodrug Approach: Stay Tuned

“…84 Thus, the less stable diastereomer was identified to have ( S p )-configuration at the phosphorus atom and corresponded to the downfield 31 P NMR signal (Figure 15). …”

“…In order to correlate unequivocally the absolute phosphorus configuration with the prodrugs’ chemical stabilities, the single diastereomers of model prodrugs, namely, phenyl esters of cyclic ( S )-HPMPA and ( S )-HPMPC, have been obtained and analyzed by X-ray crystallography and NMR . Thus, the less stable diastereomer was identified to have ( S p )-configuration at the phosphorus atom and corresponded to the more downfield 31 P NMR signal (Figure ).…”

“…X-ray crystal structures and 31 P NMR chemical shifts of ( S p )- and ( R p )-diastereomers of phenyl esters of cyclic ( S )-HPMPA prodrugs. Reprinted with permission from ref . Copyright 2012 American Chemical Society.…”

“…Possible conformer equilibria of ( R p )-diastereomers ( I – II ) (left) and ( S p )-diastereomers ( III – IV ) (right) in solution based on analysis of solvent effect on 1 H NMR coupling constant values. Reprinted with permission from ref . Copyright 2012 American Chemical Society.…”

Synthesis and crystal structure of benzyl 5-oxo-5-phenyl-2-(quinolin-2-yl)pentanoate, C27H23NO3

“…The title compound introduces a quinoline group into the ester, which increases the coordination point and fluorescent properties. For example: for medical drug research [6,7], organic synthesis reactions [8], luminescences [9], molecular sensors [10,11] and so on. The crystal structure is only built up by C 27 H 23 NO 3 molecules.…”