The goal of the Distributed Drug Discovery (D3) Program is to develop an accessible, internationally collaborative, and efficient educational lab protocol that tasks students with synthesizing antimicrobial dipeptides. Students benefit from the D3 Program by learning industry-relevant techniques and instrumentation while also contributing towards tackling the antibiotic-resistant microbe (AMR) problem. The original D3 protocol has successfully identified anti-microbial dipeptides through a solid-phase-peptide synthesis methodology, but many of the reagents utilized are hazardous or inaccessible. A primary concern to widely implement the D3 Program is to find greener reagents that are just as effective as the ones already in use. This research aimed to find replacements for piperidine, the precursor to the illicit drug phenylcyclohexyl piperidine (PCP); the explosive hydroxybenzotriazole (HOBt); and the reprotoxic dimethylformamide (DMF). Viable alternative reagents that were explored include propanephosphonic anhydride (T3P), 4-methylpiperidine, and ethyl acetate. Optimizations to the proposed “greener” protocol also include reducing solvent use in washing steps and shortening the acylation reaction time. The “greener” D3 protocol successfully achieved high purities and acceptable yields for biological screening purposes across multiple dipeptide products. Confirmation of the reproducibility of the proposed protocol in the instructional lab is still necessary; nonetheless, preliminary results suggest that the optimized protocol provides a greener alternative at no cost to performance.

Identifying greener reagent alternatives for the distributed drug discovery program

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.