Reversal of Diastereoselectivity in the Synthesis of Peptidomimetic 3‑Carboxamide-1,4-benzodiazepin-5-ones

Enantiopure
3-carboxamide-1,4-benzodiazepin-5-ones were synthesized
via the Ugi reaction followed by the Staudinger/aza-Wittig or reduction
reactions in only two steps. A complete reversal of diastereoselectivity
was achieved depending on the cyclization methodology employed. The
different orientation of the C3 substituent in our 3-substituted 1,4-benzodiazepin-5-ones
with respect to the most studied 1,4-benzodiazepin-2-ones makes them
complementary in the development of new drugs because the primary
source of binding selectivity of 1,4-benzodiazepines is the selective
recognition of ligand conformations by the receptor.