Synthesis and conformational analysis of phosphorus-derivatized no-base analogs of 3',5'-cyclic nucleotides

A number of epimeric pairs of 3-X-3-oxo-trans-2, 4, 7-trioxa-3-phosphabicyclo[4.3.0]-nonanes [5, X OCH3; X OPh; 7, X Cl; 8, X N(CH3)2; 9, X S-; 10, X O-] have been prepared as no-base analogues of 3',5'-cyclic nucleotides. 1H NMR analysis shows the phosphate ring of the cis diastereomers (relationship of singly bonded substituent on phosphorus and proton H1) 5a–7a, 9a and 10 and the trans diastereomers 8b and 9b to be in the chair conformation 15. The phosphate rings of the epimers 5b–7b and 8a exist as an equilibrium between chair conformation 15 and twist conformation 16. The mole fraction of twist depends on the nature of the singly bonded substituent and varies from about 0.3 for 5b to 0.8 for 7b. The close similarity in coupling constants of the tetrahydrofuran ring of the phosphates 5–10 indicates that the population of a twist conformer has little effect on the conformation of this ring, which is close to 4E-4T3. The results obtained for 5–10 are compared with those of conformational studies on corresponding phosphates derived from thymidine and cyclopentane.