A NOVEL SYNTHESIS OF 3'-DEOXY-3'-NITROTHYMIDINE VIA NUCLEOPHILIC-SUBSTITUTION WITH NITRITE ANION

Nucleophilic substitution at C3' of 1-(2-deoxy-5-O-trityl-beta-D-erythro-pentofuranosyl)-2-methoxy-5-methyl-4(1H)-pyrimidinone (5) with methyl iodide/triphenylphosphine/diethyl azodicarboxylate gave the expected inverted iodide 6 and minor epimer 7. Treatment of 6 with lithium nitrite/phloroglucinol yielded the desired nitro derivative 8 and subsequent acidic deprotection afforded the title compound 1. This represents a novel method for the introduction of a nitro group into the furanosyl moiety of a nucleoside. The nmr spectroscopic techniques (COSY, NOESY, nOe, HMQC and HMBC) were used to determine the stereochemistry at C3' of the nucleosides. Spectral analysis of H-D exchange at the 3'-position of 1 did not indicate the formation of its epimer 10.