PubMed1992
The cis and trans forms of thymidine methyl cyclic 3',5'-phosphate (9) and of the corresponding phenylphosphonate derivatives (10) were prepared in two steps from the corresponding cyclic amide. 1H NMR spectroscopy showed the phosphorus-containing six-membered rings of cis-9 (MeO and thymin-1-yl cis) to be in the chair conformation, but trans-9 to be approximately 40% in the twist conformation in pyridine-d6 and 33% in acetone-d6. For trans-9, there was resistance of conversion of the chair form into the twist form with the MeO group pseudo-axial with a delta G degrees(C-->T) value of 3.0 kcal/mol. Similarly, for cis-10 (23-39% twist population in CD3CN, acetone-d6, and CDCl3), a delta G degrees(C-->T) value of 0.5-0.6 kcal/mol for placement of the phosphoryl oxygen pseudo-axial was obtained. Both values are taken to be approximations for delta G degrees(C-->T) for cTMP. For trans-10, the twist conformation was populated to the extent of 6-13% with a delta G degrees(C-->T) value of 1.3 kcal/mol.