Synthesis and molecular conformation of 2',3'-O-isopropylidene-5'-deoxy-6(R),5'-cyclo-5,6-dihydrouridine

The title compound (hereafter abbreviated as 6(R),5'-cyclo-hUrd) is synthesized from 2',3'-O-isopropylidene-5'-deoxy-5'-iodouridine and its molecular structure has been determined by X-ray analysis. 6(R),5'-Cyclo-hUrd crystallizes in space group C2 with Z = 4, and unit-cell dimensions a = 11.220 (2), b = 6.393 (1), c = 18,963 (3) A and beta = 107.98 (1) degrees. The structure was solved by direct interpretation of the three-dimensional Patterson function and refined to a final R index of 0.063. In the crystal the glycosyl torsion angle chi CN is 60.7 degrees (anti conformation) and the dihydrouracil ring adopts a half-chair conformation. The puckering of the ribose ring is an unusual O(1')-exo (P = 267 degrees, tau m = 47 degrees). The coupling constants of the 1H-NMR spectrum measured in C2HCl3 solution indicate that the overall conformation of 6(R),5'-cyclo-hUrd found in crystal is also maintained in solution. The theoretical calculations of coupling constants by the finite perturbation theory (FPT) intermediate neglect of differential overlap, self-consistent field molecular orbital (INDO SCF-MO) method indicate that the deviation of the observed coupling constants of sugar ring protons from those predicted by applying modified Karplus-type formula to the X-ray structure could be due to the strains around the sugar ring carbon atoms attached by protons.