Project 1: New Phase Trafficking Methodologies
Project 1 focuses on the use of ring-opening metathesis polymerization (ROMP) for integrating the science of combinatorial library synthesis with the science of high-throughput chemical library purification. The norbornenyl ring system is utilized as a general chemical tag for incorporation into a wide variety of norbornenyl-tagged reagents, scavenging agents, phase-tracking agents, norbornenyl-tagged soluble supports, and photocleavable linkers. The PI of this project is Paul Hanson. Additional expertise will be provided by Richard Givens and Daniel Flynn (President of Chemistry at Deciphera). Click here for more information about Project 1.
Project 2: Biomimetics/Scaffolds
Project 2 is devoted to novel methodologies and scaffolds based on peptides. The focus of these efforts is a three-component ring expansion protocol that allows the streamlined synthesis of peptidomimetic libraries that contain multiple related scaffolds. In addition, related chemistry that affords useful small-molecular heterocycles using sequential "domino" processes recently uncovered in the Aubé laboratory has been added to this revised application. Jeff Aubé is the project leader. Apurba Dutta is also contributing a program in which carbohydrate scaffolds can be built onto commonly available building blocks and secondarily converted to a variety of additional novel substructures. Click here for more information about Project 2.
Project 3: Organometallic Combinatorial Chemistry
Project 3 has three main goals: (1) the design of a recyclable, chiral palladium(0)-based linker/scaffold; (2) the development of solid-supported palladium(II) and platinum(II) catalysts for electrophilic activation and subsequent functional elaboration of aromatic C-H bonds; and (3) the development of a novel, highly practical, and general iodocyclization protocol for the generation of an array of 1-iodo-2-aryl-substituted heterocycles. Building blocks with this motif will be further diversified by three alternative palladium-catalyzed cross-coupling and/or annulation processes that generate multiple new carbon-carbon bonds. Helena Malinakova is the project leader. Jon Tunge and Richard Larock are the Co-Investigators for this project. Click here for more information about Project 3.
Project 4: Natural Products & Privileged Structures
Project 4 is devoted to the development of new techniques and strategies for the synthesis of libraries of synthetic molecules based on and of comparable complexity to bioactive natural products. Keith Buszek is the project leader. Both Gunda Georg and Brian Blagg will develop methods for the synthesis of complex families of natural products (octalactin and trienomycin A, respectively). Click here for more information about Project 4.
