The preparation of natural product-inspired nucleoside analogs using solution-phase parallel synthesis is described. The key intermediates containing alkyne and N-protected amino moieties were developed to allow for further skeleton and substituent diversity using click chemistry and urea or amide bond formation. Rapid purification was accomplished using solid-phase extraction. The obtained library comprised 80 molecules incorporating two diversity positions and one chiral center, each of which was efficiently prepared in good purity and acceptable overall yield. A bacterial morphology study was also performed.
Keywords: chemical space; combinatorial chemistry; natural product-inspired nucleosides; semiautomated synthesis; uridine-containing library.