Movassaghi Group Paper Published in Angewandte Chemie

Danielle Randall
September 6, 2017

Dr. Taek Kang and Dr. Kolby White from the Movassaghi group report the first enantioselective total synthesis of (–)-deoxoapodine. Their synthesis includes an efficient molybdenum-catalyzed enantioselective ring-closing metathesis reaction, developed in collaboration with Dr. Tyler Mann from the Hoveyda group at Boston College, for desymmetrization of an advanced intermediate that introduces the C5-quaternary stereocenter. After C21-oxygenation, the pentacyclic core of the alkaloid was accessed via electrophilic amide activation and transannular spirocyclization. A biogenetically inspired dehydrative C6-etherification reaction proved highly effective to secure the F-ring and the fourth contiguous stereocenter of (–)-deoxoapodine with complete stereochemical control.

 

Enantioselective Total Synthesis of (–)-Deoxoapodine
Taek Kang, Kolby L. White, Tyler J. Mann, Amir H. Hoveyda, and Mohammad Movassaghi
DOI: 10.1002/anie.201708088

Abstract: The first enantioselective total synthesis of (-)-deoxoapodine is described. Our synthesis of this hexacyclic aspidosperma alkaloid includes an efficient molybdenum-catalyzed enantioselective ring-closing metathesis reaction for desymmetrization of an advanced intermediate and to introduce the C5-quaternary stereocenter. After C21-oxygenation, the pentacyclic core was accessed via an electrophilic C19-amide activation and transannular spirocyclization. A biogenetically inspired dehydrative C6-etherification reaction proved highly effective to secure the F-ring and the fourth contiguous stereocenter of (-)-deoxoapodine with complete stereochemical control.