Microwave-assisted stereospecific synthesis of novel tetrahydropyran adenine isonucleosides and crystal structures determination

Abstract

We describe in this article stereospecific syntheses for new isonucleosides analogs of adenine 5–7 from tosyl derivatives 2–4 accessing by microwave irradiations (50–80%). The adenine reacts entirely at the N(9) position. Compounds 2–4 were prepared in two steps from the corresponding alcohols 1, 8 and 9 (81–92%). These tetrahydropyrans alcohols 1, 8 and 9 are achiral (Meso compounds) and were prepared in two steps with complete control of 2,4,6-cis relative configuration by Prins cyclization reaction (60–63%) preceded by the Barbier reaction between allyl bromide with benzaldehyde, 4-fluorobenzaldehyde and 2-naphthaldehyde respectively under Lewis acid conditions (96–98%). The configurations and preferential conformations of 5–7 were determined by crystal structure of 6. These novel isonucleosides 5–7 present in silico potentiality to act as GPCR ligand, kinase inhibitor and enzyme inhibitor, evaluated by Molinspiration program, consistent with the expected antiviral and anticancer bioactivities.