Our research is focused on the development of concise and stereoselective synthetic methods and strategies that permit rapid access to biologically important natural products. Central to our research philosophy is an emphasis on step economy and flexibility in the overall synthetic routes. Ultimately, these processes should lend themselves to the production of sufficient quantities of the biologically-relevant targets and analogues of these substances for structure-activity profiling.

Synthetic Methodology

Chlorohydrins as natural product building blocks

The stereoselective synthesis of heterocyclic compounds is a longstanding synthetic challenge. In recent years we have made several advances in this area by exploiting α-chloroaldehydes as versatile building blocks for the synthesis of tetrahydrofuran, tetrahydropyran, and pyrrolidine-containing natural products and therapeutic leads (including carbohydrate analogues, iminosugars). These efforts rely on highly diastereoselective aldol reactions of α-chloroaldehydes, affording β-ketochlorohydrins that can be rapidly converted into stereochemically rich heterocycles and natural products. We have also reported a one-pot organocatalytic aldehyde chlorination/aldol reaction that proceeds with dynamic kinetic resolution and provides direct entry to a new class of carbohydrate building blocks.

Photocatalytic fluorination

The incorporation of a fluorine atom into a bioactive molecule is a strategy commonly used in medicinal chemistry to impart substantial changes in the physicochemical parameters of the molecule. The selective and mild fluorination of complex organic molecules is therefore of great interest to the biomedical research community. We have recently discovered a method for the direct fluorination of unactivated C-H bonds.

This reaction utilizes the decatungstate anion and N-fluorobenzenesulfonamide (NFSI) for photocatalytic hydrogen atom abstraction and fluorine atom transfer respectively. Of all the recently disclosed photocatalytic C-H fluorinations, the decatungstate/NFSI system displays unprecedented functional group tolerance, able to cleanly fluorinate unprotected amino acids and peptides. Current work in this area involves exploring the scope and limitations of our fluorination reaction with a goal of assisting medicinal chemistry efforts. Furthermore, a collaboration with TRIUMF - Canada's national nuclear physics laboratory- has allowed us to fluorinate compounds with 18F for use in positron emission tomography (PET) imaging.

Natural Product Synthesis

Natural product targets are selected based on their putative therapeutic activity, for structural/stereochemical assignment, and/or intriguing molecular architecture. Our completed targets are shown below.

Completed Targets: