Distributed Drug Discovery: Advancing Chemical Education through Contextualized Combinatorial Solid-Phase Organic Laboratories.

The Distributed Drug Discovery (D3) program trains students in three drug discovery disciplines (synthesis, computational analysis, and biological screening) while addressing the important challenge of discovering drug leads for neglected diseases. This article focuses on implementation of the synthesis component in the second-semester undergraduate organic laboratory. The educational program was started at IUPUI in 2003 and has been carried out over 23 semesters with 65 lab sections by >1200 students. Since the chemistry component is most advanced, it serves as a model for the computational and biological modules in development. Synthetic procedures are based on well-documented, reproducible solid-phase combinatorial chemistry. They are carried out in a 2 × 3 combinatorial grid (Bill-Board) to create a control molecule and five new products (50 μmol scale, ∼10–20 mg product, typically high LC/MS purity). The first of these synthetic procedures (D3 Lab 1) utilizes a protected and activated derivative of g...