DOS Methodologies

Diversity-Oriented Synthetic Approaches to Sultams

The Hanson group has an ongoing interest in the development of novel methods for the design and synthesis of diverse S- and P-heterocycles as potential small molecule drug probes/leads. Utilizing a diversity-oriented synthesis (DOS) approach in combination with a variety metrics (bioinformatics), a number of protocols have been recently developed to access collections of diverse S-heterocycles, namely sultams. Highlights include a “Click, Click, Cyclize” approach, complementary ambiphile pairing (CAP) and reagent-based DOS.

These sultam libraries are generated utilizing a combination of soluble, ROMP-derived oligomeric reagents and scavengers with a variety of reaction platforms (MACOS, Microwave, Flow-through, Chemspeed). All compounds generated utilizing these protocols undergo High-Throughput Screening (HTS) within the NIH-Molecular Library Probe Center Network (MLPCN) and Chemical Methodology Library Development (CMLD) Network for screening of potential biological activity. Currently, a number of HTS bioactive sultam hits are undergoing medicinal chemistry follow-up and structural activity relationship (SAR) evaluation in collaborative projects between our group, the corresponding screening centers, bioinformatics and medicinal chemists.

DOS strategy and a representative application in the synthesis of sultam libraries:

figure 10

Recent Reported Highlights


figure 11


figure 12


figure 13

KU Today
One of 34 U.S. public institutions in the prestigious Association of American Universities
44 nationally ranked graduate programs.
—U.S. News & World Report
Top 50 nationwide for size of library collection.
23rd nationwide for service to veterans —"Best for Vets," Military Times