Influence of phosphorus derivatization on the conformational behavior of model compounds for 3',5'-xylo-cAMP studied by proton NMR spectroscopy

A number of epimeric pairs of 3-X-3-Y-cis-2,4-dioxa-3-phosphabicyclo[4.3.0]nonanes (2, X = OCH3, Y = 0; 3, X = OCH3, Y = S; 4, X = OPh, Y = O; 5, X = OPh, Y = S; 6, X = Cl, Y = 0; 7, X = Cl, Y = S; 8, X = N(CH3)2, Y = 0; 9, X = N(CH3)2 Y = S; 10, X = S-, Y = 0; 11, X = 0-, Y = 0) has been prepared as model compounds for 3',5'-xylo-cAMP (1). The influence of the nature and orientation of the exocyclic phosphorus substituents on the phosphate ring conformation has been determined by 1H NMR. It is shown that the cis phosphates 2a-7a and the trans phosphates 8b and 9b populate the same chair conformation as was found for 3',5'-xylo-cAMP. However, the phosphate rings of their epimers exist as an equilibrium between this chair conformation and a distorted-boat conformation. The mole fraction of the latter conformer depends on the nature of the exocyclic phosphorus substituent and varies from 0.14 for the phosphoramidate 9a to 0.86 for the chlorophosphonate 7b. For the phosphates 10a, 10b, and 11, the conformation of the dioxaphosphorinane ring is strongly affected by the exact location of the negative charge on the phosphate group.