Asymmetric syntheses of piperidino-benzodiazepines through 'cation-pool' host/guest supramolecular approach and their DNA-binding studies

The asymmetric synthetic approach to piperidino-benzodiazepine 4a (a homolog of DC-81) has been developed The absolute stereochemistry of 4 and 5 has been assigned to be (S) at C-12a position This procedure features the use of a canon-pool strategy and also a host/guest supramolecular co-catalysis approach In this study the chloroformate of 8-phenylmenthyl has been employed as a chiral auxiliary and includes one-pot conditions for anodic oxidation which are followed by nucleophilic addition to an N-acyliminium ion In addition intramolecular azido reductive-cyclization and nitro reductive dithioacetal deprotective tandem-cyclization approaches have also been utilized for the syntheses of these compounds 4a b and 5a b Some of the representative compounds exhibited an enhanced DNA-binding ability in comparison to the natural product DC-81 (C) 2010 Elsevier Ltd All rights reserved