Synthesis of Enantiomerically Pure 1,2-Diamine Derivatives of 7-Azabicyclo[2.2.1]heptane. New Leads as Glycosidase Inhibitors and Rigid Scaffolds for the Preparation of Peptide Analogues

Enantiomerically pure alcohols (−)- and (+)-7-tert-butoxycarbonyl-6-endo-p-toluenesulfonyl-7-azabicyclo[2.2.1]hept-2-en-5-endo-ol ((−)-11 and (+)-11) have been obtained from the Diels−Alder adduct of N-(tert-butoxycarbonyl)pyrroel and 2-bromo-1-p-toluenesulfonylacetylene, including a resolution method. These two alcohols were converted into (+)- and (−)-5-exo-amino-7-(tert-butoxycarbonyl)-2,3-exo-isopropylidenedioxy-7-azabicyclo[2.2.1]heptane ((+)-18 and (−)-18) and (+)- and (−)-5-endo-amino-7-(tert-butoxycarbonyl)-2,3-exo-isopropylidenedioxy-7-azabicyclo[2.2.1]heptane ((+)-19 and (−)-19) after adequate functionalization and desulfonylation steps. The corresponding conformationally constrained bicyclic 1,2-diamines (+)-4, (−)-4, (±)-5, (±)-6, (+)-7, and (−)-7 were obtained from the protected precursors 18 and 19 and evaluated as glycosidase inhibitors. Diamines (+)-4, (−)-4, (+)-6, and (−)-6 can be seen as new nonpeptide molecular scaffolds for the design of peptide analogues.