Synthetic Chemistry

In collaboration with the Chemical Biology Platform, the Chemical Biology Program is identifying the principles that underlie diversity-oriented synthesis (DOS) and piloting new DOS pathways. Diversity synthesis is used to achieve a complete synthesis of an optimal small-molecule screening collection; the features that define this collection are discussed in the chemistry activities of the Therapeutics Platform. The Program’s efforts in Synthetic Chemistry are described in more detail below.

Pathway development. The use of small molecules to probe normal and disease-associated biological phenomena is an important aspect of modern chemical biology. Intrinsic to this approach is the need for a collection of molecules to screen against a wide variety of biological areas. Determining which molecules to include within a screening collection and how to obtain them rests firmly on the field of synthetic organic chemistry. Within the Chemical Biology Program, we develop synthetic pathways aimed at generating biologically active molecules. Our focus is on the design and execution of pathways that deliver diverse small molecules in a highly efficient manner.
 
Pathway development is largely supported under the NIGMS-funded Centers of Excellence in Chemical Methodology and Library Development (CMLD).
 
Methods development. The generation of new synthetic methods to drive the assembly of a screening collection of small molecules is a central focus within the Chemical Biology Program. Method development is conducted with the aim of expanding chemical diversity in novel and highly efficient ways. In addition to reaction development, new technology platforms and instrumentation are often applied to enhance small-molecule synthesis.
 
Cheminformatics research. Molecules generated from our synthesis efforts are inherently done so for the purpose of examining their biological properties. The outcomes of this biological evaluation are now being examined over large amounts of screening data in hopes of gaining new insights to drive future synthesis activities. This is made possible by the development of new computational methods that allow disparate data types to be comparatively analyzed. More specifically, the performance of compounds based on source (i.e., commercial, natural) can be comparatively examined. Performance in biological screening is now being linked to synthetic pathway decision-making. These two efforts alone and in tandem will begin to supply chemists with knowledge that aims to more accurately direct their synthetic activities.
 
For more detail on our efforts in this area, see Cheminformatics research.