Total Synthesis of Dragocins A−C through Electrochemical Cyclization
Brendyn P. Smith, Nathanyal J. Truax, Alexandros S. Pollatos, Michael Meanwell, Pranali G. Bedekar, Alberto F. Garrido‐Castro, Phil S. Baran
Abstract
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.