Parallel Solution-Phase Synthesis of an Adenosine Antibiotic Analog Library

A library of eighty one adenosine antibiotic analogs was prepared under the Pilot Scale Library Program of the NIH Roadmap initiative from 5′-amino-5′-deoxy-2′,3′-O-isopropylidene-adenosine 3. Diverse aldehyde, sulfonyl chloride and carboxylic acid reactant sets were condensed to 3, in solution-phase fashion, leading after acid-mediated hydrolysis to the targeted compounds in good yields and high purity. No marked anti-tuberculosis or anticancer activity was noted on preliminary cellular testing, but these nucleoside analogs should be useful candidates for other types of biological activity.