Projects

Core research programs in leading edge methodology for streamlined organic synthesis of complex molecules are being developed in the following areas: 

• Development of novel heterogeneous reagents and catalysts: A variety of polymer-based reagents and "scavenger" resins have been devised to facilitate parallel solution-phase synthesis.   In addition to developing novel, second-generation bound reagents and scavengers, new heterogeneous reagents utilizing other medias (e.g. silica, silicates, and other biomineral supports) will be developed and investigated for use in multistep synthesis, either using batch or column (flow) formats.  Approaches utilizing “mixed-beds” of heterogenized reagents and catalysts in multistep syntheses will be emphasized, along with one-pot multistep reaction sequences. 

• Development of Novel Affinity-Tagged Reagents:   In many cases, it is desirable to develop reagents or reactants which may be selectively removed from reaction mixtures by simple filtration using highly chemoselective affinity media.  Several projects are being initiated to develop such strategies where compounds are "tagged" with orthogonal affinity handles, allowing facile sequestration from reaction mixtures by simple filtration.  Such reagents allow one to carry out reactions using soluble, small molecule reagents, and rapidly purify intermediates and products. 

• New methods for Streamlined Asymmetric Synthesis:  A major methodology gap exists currently in the development of parallel, single-isomer chiral synthesis methods.  A core project of the CSS will be to develop chiral synthesis transformations utilizing solid supports in the synthesis single isomer compounds.  A significant emphasis will be placed on the development of strategies wherein the initial resin loading step is a highly enantioselective transformation.  In addition, the development of catalysts and reagents for the rapid, parallel synthesis of enantio-enriched compounds in solution phase will be investigated. 

• Convergent Combinatorial Synthesis of Complex Molecules:   The majority of  parallel synthesis strategies that are being performed currently utilize linear synthesis sequences.  Historically, convergent routes have been utilized in natural products synthesis to prepare complex molecules due to yield advantages and ready modification of problematic fragments.  A major impetus for the development of novel streamlined synthesis approaches and reagents will be their application in the convergent synthesis of complex natural-product like molecules. We will develop highly convergent fragment coupling reactions to permit parallel synthesis of complex molecules such as polyketides and related structures.  Fundamental issues such as the development of efficient protecting group strategies will also be addressed. 

• Streamlined Approaches to Heterocyclic Chemistry:  New and fundamental transition metal-mediated approaches to the synthesis of heterocycles are being developed which will form the basis for a number of CSS projects.  Many of these approaches rely on coupling reactions involving multiple polymer systems.