Pyridine Coenzyme Analogues. 3. Synthesis of Three NAD+ Analogues Containing a 2'-Deoxy-2'-substituted Nicotinamide Arabinofuranosyl Moiety

Article abstract of DOI:10.1021/jo00011a029

A general method for the preparation of 2'-deoxy-2'-substituted arabino-nicotinamide-adenine dinucleotide (NAD) analogues is described.Starting from 1,2:5,6-di-O-isopropylidene-α-D-allofuranose, the 2'-amino-, 2'-azido-, and 2'-fluoro-arabino-NAD analogues have been prepared.We report an improved phosphorylation procedure for nicotinamide nucleosides using pyrophosphoryl chloride in m-cresol.The selective reduction of azido substituents by aqueous dithiothreitol (DTT) in the presence of the readily available nicotinamide moiety is also reported.With both the 2'-azido and the 2'-fluoro substituents the cis configuration predominates for the incoming nicotinamide, thus allowing the steroselective formation of the β anomer in high yield.