Synthesis of peptidomimetics, δ- and ε-lactam tetrazoles

A concise two-step procedure for the synthesis of novel delta-lactam tetrazoles has been established via the Ugi-azide reaction using 5-oxohexanoic acid along with primary amines, isocyanides, and azidotrimethylsilane followed by 1,1'-carbonyldiimidazole-mediated intramolecular amide formation. Expansion to -lactam tetrazole scaffolds was accomplished using methyl 6-oxoheptanoate via the same Ugi-azide reaction followed by basic hydrolysis and SOCl2 activation to enable lactam formation.