Total synthesis of heterocyclic natural products, development of methodology for organic synthesis, mechanistic organometallic chemistry, synthesis of complex oligosaccharides and glycoprotein derivatives, chemistry of hypervalent silicon derivatives, synthesis of nanoparticles and functionalized nanomaterials for applications in drug delivery, diagnostics and biosensing.
Major Recognitions and Honors
Significant Professional Service and Activities
Dr. DeShong is the founder and Chief Scientific Officer of SD Nanosciences, Inc. of Beltsville, MD. The focus of the company is to develop novel methods for the detection and treatment of pathogenic infections and cancer. In addition, Dr. DeShong has consulted for >15 companies on problems related to synthetic and pharmaceutical chemistry.
Dr. DeShong has supervised the Ph.D. and Masters theses of 50 graduate students. In addition, 8 postdoctorals and 45 undergraduates have performed research in his laboratory.
Siloxane Chemistry. A significant area of research in Professor DeShong’s group focuses on development of new strategies for the stereoselective synthesis of heterocyclic systems and the application of these approaches to the preparation of natural products and biologically active substances.
The DeShong group has demonstrated that hypervalent silicates can be employed for carbon-carbon bond couplings employing palladium catalysis. This coupling strategy that is similar to Suzuki (boron compounds) and Stille (tin compounds) couplings has been employed for the synthesis of unsymmetrical biaryls and allylic couplings. Applications of this strategy to the synthesis of antimitotic agents colchicine and steptonigrin, and the antitumor antibiotic pancratistatin are underway. These investigations include new methods for the synthesis of siloxane derivatives and the use of siloxane polymers for the synthesis of combinatorial libraries.
Carbohydrate and Glycoprotein Synthesis. Another area of research has been the discovery that hypervalent silicate anions are able to function as nucleophilic surrogates for fluoride, cyanide, and azide anions as shown in the scheme left. Silicate anions are produced by the reaction of ammonium fluorides with the appropriate trisubstituted silane. The resulting silicate anion has proven to be a “super nucleophile” under extremely mild conditions in substitution sequences. This approach is being extended to the transfer of other nucleophiles, including carbon nucleophiles such as acetylides and enolates. The azide chemistry developed in this project has been utilized for the synthesis of glycoconjugates such as N-linked glycoproteins (see below), lipid A toxins and inhibitors of glycosyltransferases.
Functionalized Nanomaterials. Applications of the carbohydrate technology to the the preparation of functionalized nanomaterials for diagnostics and drug delivery are underway. This multidisciplinary collaboration with materials engineers and cell biologists (Drs. English, Zachariah, Stein, Dagenais, Ghandehari, Nan) has demonstrated that nanostructures (gold, silica, alumina, and other materials) with interesting morphologies and/or properties can be functionalized with complex oligosaccharide and peptide conjugates that impart a variety of unique characteristics to the nanomaterial. First, these coatings typically result in the formation of materials that are stable in biological fluids indefinitely. In addition, the coatings can be tailored to target the nanostructures to specific cell types resulting in systems that are ideal for diagnostic and drug delivery applications.
The focus of our studies are to develop a “Molecular Toolbox” of general methodology for the functionalization of a wide variety of materials, to synthesize oligosaccharide conjugates that will “target” specific cell populations (pathogens and tumors), and to measure the release profiles of the functionalized nanomaterials.
A. TEM image of porous silica nanoparticles coated with oligosaccharide cell surface conjugates. B. Hollow silica nanoparticles. C. Confocal microscope image of porous silica nanoparticles filled with antitumor antibiotic doxorubicin.