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

Abstract

AbstractThe 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 1H‐, 19F‐, and 13C‐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 2′E to 3′E going along with a reduction of the puckering amplitude τm by ca. 10–13° 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.