Total Synthesis of Dragocins A-C through Electrochemical Cyclization

The first total synthesis of dragocins A-C, remarkable natural products containing an unusual C4' oxidized ribose architecture bridged by a polyhydroxylated pyrrolidine, is presented through a route featuring a number of uncommon maneuvers. Several generations towards the target molecules are presented, including the spectacular failure of a key C-H oxidation on a late-stage intermediate. The final route features rapid, stereocontrolled access to a densely functionalized pyrrolidine and an unprecedented diastereoselective oxidative electrochemical cyclization to forge the hallmark 9-membered ring. Preliminary studies suggest this electrochemical oxidation protocol is generally useful. An electrochemical cyclization is leveraged to forge the central 9-membered ring in the hybrid metabolites dragocins A-C. The route features several stereocontrolled reactions to address the stereotetrad of the pyrrolidine fragment and a penultimate decarboxylative chlorination and global deprotection to furnish both dragocins B and C. Dragocin A was prepared through simple methanolysis of dragocin C.+ image