Acetylation of Nucleosides by N-Acetoxy-N-arylacetamides: Dependence on Base, Aryl Group, and Buffer Composition

Article abstract of DOI:10.1021/jo00137a021

Nucleosides treated with the carcinogen N,O-diacetyl-4-stilbenylhydroxylamine (1) in water and acetone are alkylated on the bases, and only alkylation products have been detected so far.In phosphate buffer at the same pH, adenosine and guanosine are acetylated on ribose, as determined by gas chromatography-mass spectrometry, in about the same yield as the total alkylation products.This acetylation does not take place in salt solution of the same pH and ionic strength.No alkylation or acetylation of adenosine or guanosine could be detected upon treatment with N,O-diacetyl-1-naphthylhydroxylamine (6), which solvolyzes at a rate comparable to that of 1, but cytidine was converted in low yield to N⁴-acetylcytidine.The results with 1 point out that apparently innocuous changes in medium may greatly alter the reactivity characteristics of some ultimate carcinogens, while the results with 6 indicate that steric hindrance in the ultimate carcinogen itself may completely alter its mechanism of decomposition from that expected.The biological consequences of these acylation reactions are unknown, although 6 has been tested for both mutagenic and carcinogenic activity and found inactive.