4′-Oxo-nucleosides. Synthesis and properties of 6-chloro-9-(6-deoxy-α-L-Iyxo-hexopyranos-4-ulosyl)purine and the corresponding 7-glycosyltheophylline

Abstract

The first synthesis of 7- and 9-linked 4′-oxo-deoxynucleosides has been accomplished by direct oxidation of sterically hindered 6-deoxyhexosylpurines by the Pfitzner–Moffatt system; use of the dimethyl sulphoxide–acetic anhydride system led only to a 4′-methylthiomethyl ether. The intermediate 7-(α-L-rhamnopyranosyl)theophylline and 6-chloro-9-(α-L-rhamnopyranosyl)purine were obtained by direct acid-catalysed fusion of theophylline and 6-chloropurine with 1,2,3,4-tetra-O-acetyl-α-L-rhamnose. A conformational inversion taking place on acetal formation from the 6-chloropurine nucleoside was revealed by n.m.r. spectral analysis. the behaviour in acidic and alkaline media of the 4′-oxohexosyl-purines has been studied. The oxo-nucleosides showed growth inhibitory activity against KB cells, whereas the parent nucleosides were inactive.