Enantioselective total synthesis of the osteoclastogenesis inhibitor (+)–symbioimine

ORGN 298

Regan J. Thomson, r-thomson@northwestern.edu and Justin Kim. Department of Chemistry, Northwestern University, 2145 Sheridan Rd, Evanston, IL 60208
Isolated in 2004 by Uemura and coworkers, (+)-symbioimine has attracted interest within the synthetic community due to its unusual 6,6,6-tricyclic iminium ring system and its demonstrated inhibition of osteoclastogenesis (EC50 = 44 μg/mL). As such, symbioimine (or analogs) may offer a new entry point into the development of preventative treatments for osteoporosis. Our enantioselective synthesis of (+)-symbioimine features a convergent enol silane addition into a dimethyl acetal promoted by TMSOTf, and involves the execution of a putative biomimetic intramolecular iminium ion promoted Diels–Alder reaction to build four of the five requisite stereocenters.

 

Total Synthesis of Complex Molecules
1:00 PM-4:40 PM, Monday, March 26, 2007 McCormick Place East -- Room E352, Level 3, Oral

Division of Organic Chemistry

The 233rd ACS National Meeting, Chicago, IL, March 25-29, 2007