Research

Research highlight in Dr. Wang’s laboratory:

Research interests: Organic synthesis, asymmetric catalysis, carbohydrate chemistry, green chemistry, supramolecular chemistry.

Our group has been focusing on the synthetic methods development of chiral compounds especially compounds of biological interests and the synthesis and characterization of new functional biomaterials. The ongoing projects include the synthesis of chiral small molecules such as chiral heterocycles, conformationally restricted bicyclic amino acids, and natural products and their analogs. We are also studying new catalytic reactions including using organocatalysts and organometallic agents. Another main research area is the synthesis and characterization of glycoconjugates and carbohydrate based functional soft-materials such as hydrogels and organogels.  

I.  Synthesis of Chiral Small Molecules and Medicinally Interesting Compounds

Despite the structural diversity of pharmaceutical compounds, certain core structures frequently appear in different classes of drugs. For example, chiral amino alcohols and nitrogen, oxygen containing heterocycles are especially important. A few structures containing these features are shown here. The antibacterial drug Linezolid (1) and anticoagulant Rivaroxaban (2) both contain oxazolidinone core structure, antibiotic Moxifloxacin (3) and antiviral agent Crixivan (4) contain other nitrogen based heterocycles. We are developing synthetic strategies for important chiral small molecules and drug-like compound libraries. Currently we are focusing on the synthesis of compound libraries that could lead to novel antimicrobial and anti-cancer agents.

Figure 1. Structures of a few synthetic drugs

Aeruginosins are natural products isolated from Microcystis aeruginosa and marine sponges.  They are small linear peptides containing an unusual bicyclic amino acid core structure, 2-carboxy-6-hydroxyoctahydroindole (Choi). Many of these compounds are serine protease inhibitors. Some compounds (5-7) in this class are shown in Figure 2. We are interested in finding structure features that can differentiate the binding sites among different serine proteases, especially thrombin and trypsin. Besides these classes of oligopeptides, we are also working the structure modifications of macrolides such as erythromycin and azithromycin shown in Figure 3, novel derivatives are synthesized and evaluated as potential drug candidates through collaboration.

Figure 2. Structures of a few biologically active natural products, aeruginosins.   

Figure 3. Structures of erythromycin and other macrolides.   

II. Synthesis and study of carbohydrate based self-assembling systems

Carbohydrates are the most abundant natural products and renewable resources on earth. With the growing world demand on energy and oils, carbohydrate based biomass will become more important as a source for raw materials and energy. Carbohydrates have been more and more recognized for their important biological roles such as mediating signal transduction, cell growth and adhesion. From a chemistry point of view, carbohydrates have multiple chiral centers that can be selectively functionalized to produce chiral building blocks for asymmetric synthesis and advanced materials. We are interested in utilizing the chirality of sugars and obtain new materials or chiral intermediates by simple transformations.

For the past several years, my group has also been working on the synthesis and self-assembling of monosaccharide derivatives, and discovered several novel classes of sugar based low molecular weight gelators (LMWGs). LMWGs are small molecules that can self-assemble to form reversible supramolecular gels in organic solvents or water. These compounds form unique classes of soft materials that are useful in biomedical research and as advanced functional materials. As shown in the figure below, the typical classes of LMWGs (I and II) were synthesized from glucose and N-acetyl glucosamine. We have systematically studied their gelation properties and gained a great deal of experiences in functionalization of monosaccharides and a good understanding of the structure and gelation properties correlation in different solvents.

Figure 4. General structures of sugar derived LWMG, gel pictures and optical images of the gel

Carbohydrates contain all of the important elements needed to prepare highly functional and synthetically flexible compounds. The creation of novel functional biocompatible materials from naturally abundant carbohydrates is very important for the advancement of carbohydrate chemistry, material science, biotechnology, and the biomedical field. The formation of hydrogels or organogels by small molecules in aqueous or organic solvents can be used for preparing novel materials. Biocompatible functional small molecule hydrogelators derived from carbohydrates and amino acids are of great interest because of the potential applications in drug delivery, tissue engineering, etc. In our research, novel carbohydrate based low molecular weight hydrogelators and other functional materials are synthesized and characterized. Their applications in enzyme immobilization and biosensors, as well as controlled release media, are being explored.  These novel functional carbohydrate based organogelators are expected to be useful in forming matrices for macromolecule encapsulation and separation, biosensors, chemosensors, and drug delivery. Our research effort should also contribute significantly to biomaterials research in tissue engineering, drug delivery, and bimolecular recognition.

III. Asymmetric Synthesis and Reactions by New Catalysts

In the area of synthetic methodology development, we have studied multiple component reactions and developed carbohydrate based organocatalysts. For research using new ligands for organometallic agents, we are currently collaborating Dr. Chris Senanayake and Dr. Carl Bussaca and Dr. Steve Han at the Chemical Development Division at Boehringer Ingelheim Pharmaceuticals (BI), the company has provided summer internship opportunities for several of my graduate students, which is very beneficial for the students. We are carrying out collaborative research in the areas of synthesizing new chiral ligands for organometallic catalysts, and new synthetic methodology studies for the preparation of chiral intermediates that are useful for pharmaceutical industry.

Current Research