A Scaffold-Diversity Synthesis of Biologically Intriguing Cyclic Sulfonamides.

A "branching-folding" synthetic strategy that affords a range of diverse cyclic benzo-sulfonamide scaffolds is presented. Whereas different annulation reactions on common ketimine substrates build the branching phase of the scaffold synthesis, a common hydrogenative ring-expansion method, facilitated by an increase of the ring-strain during the branching phase, led to sulfonamides bearing medium-sized rings in a folding pathway. Cell painting assay was successfully employed to identify tubulin targeting sulfonamides as novel mitotic inhibitors.

Regioselective reductive cleavage of bis-benzylidene acetal: stereoselective synthesis of anticancer agent OGT2378 and glycosidase inhibitor 1,4-dideoxy-1,4-imino-l-xylitol.

A highly regioselective reductive cleavage of the bis-benzylidene acetal of D-mannitol was performed using a BF(3) x Et(2)O/Et(3)SiH reagent system. A chiral intermediate 6 thus obtained was efficiently utilized in the stereoselective synthesis of the anticancer agent OGT2378 (3) and glycosidase inhibitor derivative N-tosyl 1,4-dideoxy-1,4-imino-L-xylitol (22). Chemoselective reduction of azido epoxide 10 followed by regioselective intramolecular cyclization of amino epoxide 11 resulted in the exclusive formation of deoxyidonojirimycin derivative 12.