Synthesis and Crystal Structures of O-2 `,3 `-Cyclic Cyclopentanone and Cyclohexanone Ketals of the Cytostatic 5-Fluorouridine

Abstract

The synthesis of two O-2',3'-cyclic ketals, i.e., 5 and 6, of the cytostatic 5-fluorouridine (2), carrying a cyclopentane and/or a cyclohexane ring, respectively, is described. The novel compounds were characterized by H-1-, F-19-, and C-13-NMR, and UV spectroscopy, as well as by elemental analyses. Their crystal structures were determined by X-ray analysis. Both compounds 5 and 6 show an anti-conformation at the N-glycosidic bond which is biased from ac to ap compared to the parent nucleoside 2. The sugar puckering is changed from E-2' to E-3' going along with a reduction of the puckering amplitude tau(m) by ca. 10-13 degrees due to the ketalization. The conformation about the sugar exocyclic bond C(4')-C(5') of 5 and 6 remains unchanged, i.e., g(+), compared with compound 2.