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:

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Recent Reported Highlights


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