Synthesis and structural studies of Sp and Rp diastereomers of deoxyxylo-thymidyl-3'-O-acetylthymidly (3',5')-O-(2-cyanoethyl)phosphorothioate in solution and in the solid state

The synthesis and full assignment of the molecular structure of the diaster eomers of deoxyxylothymidyl-3'-O-acetylthymidyl (3',5')-O-(2-cyanoethyl)pho sphorothioate (1) in the liquid phase based on H-1, C-13, 1D and 2D homo- a nd heteronuclear PFG (Pulse Field Gradient) NMR spectroscopic experiments a re reported. The pseudorotation parameters of deoxyribose and deoxyxylose w ere analyzed by means of the PSEUROT program. The absolute configuration Rp and Sp Of the phosphorus centers was deduced from H-1 ROESY experiment. Th e P-31 CP/MAS technique was used to establish the ratio between the amorpho us and crystalline phases, and to test the progress of crystallization. The differences in the P-31 delta (ii) principal elements of the chemical shif t tenser, in particular the delta (33) parameter, for crystalline and amorp hous phases were calculated Finally, the X-ray data for the Sp diastereomer are reported. The influence of weak C-H S hydrogen bonding on the molecula r packing of both R-p-1 and S-P-1, and the significance of this type of int ermolecular interaction for phosphorothioate systems is discussed.