The development of natural product leads beyond initial identification requires a ready supply of material for downstream studies, and is often a bottleneck for natural products development. Our laboratory is interested in creating synthetic routes to compounds discovered in-house for both medicinal chemistry optimization, and creation of chemical probes for target identification. The objective of this effort is to use established synthetic organic chemistry methods to create facile routes to either the native natural product (where appropriate), or to simplified analogues (where structures are too complex for ready synthetic access).
Straightforward synthetic access to lead compounds provides opportunities to engage in hit-to-lead medicinal chemistry optimization and compound library synthesis, supported by the high-content screening tools developed by our lab through the SFU Chemical Screening Center. In addition to library design and development, we are also interested in creating derivatives of natural products to assist with target identification. To accomplish this synthetic organic chemistry methods are employed to generate both semi-synthetic and de novo synthesized probe compounds containing a variety of functional groups including biotinylated, photoaffinity, stationarily immobilized and fluorescent derivatives, which can be used to determine compound molecular targets.