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Nucleosides. CIX. 2′‐Deoxy‐ψ‐isocytidine, 2 ‐deoxy‐ψ‐uridine, and 2′‐deoxy‐l‐methyl‐ψ‐uridine. Isosteres of deoxycytidine, deoxyuridine and thymidine

1977; Wiley; Volume: 14; Issue: 6 Linguagem: Inglês

10.1002/jhet.5570140641

1943-5193

C. K. CHU, U. REICHMAN, Kyoichi A. Watanabe, Jack J. Fox,

Biochemical and Molecular Research

Abstract 2′‐Deoxy‐ψ‐isocytidine (VIIβ), a 2′‐deoxy analog of antileukemic ψ‐isocytidine and also a C ‐nucleoside analog of deoxycytidine, was synthesized from ψ‐uridine by making use of the newly discovered pyrimidine to pyrimidine transformation reaction [ J. Chem. Soc. , 14, 537 (1977)]. 2′‐Deoxy‐ψ‐uridine (IIβ) and 2′‐deoxy‐l‐methyl‐ψ‐uridine (V), both C ‐nucleoside analogs of deoxyuridine and thymidine, were also synthesized. ψ‐Uridine was converted into the 2′‐chloro analogs (I) which was reduced with tributyltin hydride to give an α,β‐mixture of 2′‐deoxy‐ψ‐uridines. The β‐isomer (11β was trimethylsilylated and the product (III) treated with methyl iodide to afford the 1‐methyl derivative (IV). After hydrolytic removal of the trimethylsilyl groups from IV, the thymidine analog (V) was obtained in good yield. A crude mixture of II was converted in good yield into an α,β‐mixture of 1,3‐dimethyl‐2 ‐deoxy‐ψ‐uridines (VI) by treatment with DMF dimethyl acetal in DMF. Treatment of the β‐isomer (VIβ) with guanidine, however, gave the α,β‐mixture of 2 ‐deoxy‐ψ‐isocytidines (VII). The pure β‐isomer (VIIβ) was obtained by thick layer chromatography. The pure α‐isomer (VIIα) was obtained when VIα was treated with guanidine. 2 ‐Deoxy‐ψ‐isocytidine (VIIβ) and 2 ‐deoxy‐l‐methyl‐ψ‐uridine (V) exhibited inhibitory activity against P815 cells (ID 5 0 1.2 μg./ml. and 4.9 μg./ml., respectively) and the thymidine analog V was found to be active against Streptococcus faecium var. duran . J. Heterocyclic Chem. , 14, 1119 (1977)