New methodologies for the generation of diverse sultam libraries utilizing ROM polymerization

ORGN 72

Alan Rolfe, arolfe@ku.edu, Kelly Volp, Kyle Young, and Paul R. Hanson, phanson@ku.edu. Department of Chemistry, University of Kansas, 1251 Wescoe Hall Dr, NIH Center of Excellence in Chemical Methodologies and Library Development (KU-CMLD), Lawrence, KS 66045-7582
The developments of new methods to generate fused-bicyclic sulfonamide scaffolds (sultams) for library production are reported. The first approach employs a key domino Heck-Aza-Michael approach for the synthesis of 1,2-benzisothiazoline-3-acetic acid 1,1-dioxides. Expansion of the method to a one-pot, multi-component protocol to generate diverse sultams from a range of commercially available α-bromobenzenesulfonyl chlorides, amines and Michael acceptors is reported. The second utilizes an Intramolecular Diels-Alder (IMDA) approach from commercial amino acids to afford structurally diverse, tricyclic sultams. From these scaffolds a range of diverse libraries has been synthesized using a variety of technical platforms including Chemspeed and Bhodan Block. Scaffold design allows for further diversification utilizing high-load soluble ROMP reagents and scavengers in a facilitated protocol, avoiding classical work-up procedures.

 

Physical Organic Chemistry, Combinatorial and Process Chemistry, New Reactions and Methodology, Peptides, Proteins and Amino Acids
8:00 PM-10:00 PM, Sunday, April 6, 2008 Morial Convention Center -- Hall A, Poster

Division of Organic Chemistry

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008