Nucleosides and Nucleotides. Part 2: Synthesis of both anomers of 1‐(5′‐O‐phosphoryl‐2′‐deoxy‐ D ‐ribofuranosyl)‐2(1 H )‐pyridone [1]

The two anomeric 1‐( 2′ ‐deoxy‐ D ‐ribofuranosyl)‐2(1 H )‐pyridones 6 and 7 were synthesized from 2‐pyridone and 3,5‐di‐(O‐ p ‐toluoyl)‐2‐deoxy‐ D ‐ribofuranosyl chloride ( 2 ) via the di‐O‐ p ‐toluoyl derivatives 3 and 4 using the mercuric halide procedure. Phosphorylation of the nucleosides 6 and 7 by bis‐( 2,2,2 ‐trichloroethyl)‐chlorophosphate gave the phosphate esters 8 and 9 together with some 2 ‐(bis‐[ 2,2,2 ‐trichloroethyl]‐phosphoryloxy)‐pyridine 10 , which proved to be very labile. Structure and configuration of compounds 6 to 9 were established by spectral methods, the configurations being derived from the chemical shifts of the sugar protons and the splitting patterns of the anomeric protons (‘triplet‐quartet rule’). The specific rotations of 3 , 4 , 6 , 7 , 8 and 9 show that the three pairs of anomers represent exceptions to Hudson's rule of isorotation. Reductive removal of the trichloroethyl groups in 8 and 9 with zinc proceeds stepwise, yielding the phosphoro‐diesters 13 and 14 and the two desired anomeric 5′‐nucleotides 15 and 16 . These latter were purified and characterised as the ammonium salts. Enzymatic cleavage by the 5′‐nucleotidase of Crotalus adamanteus venom took place only in the ‘natural’ β‐series. The ‘unnatural’ α‐anomers were resistent to the enzyme. The structure of 10 was established by spectral methods and confirmed by synthesis.