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Synthesis of Organic Products In spired by Natural Compounds
life sciences Synthesis of Organic Products Inspired From Natural Compounds
Sneha Makhijani
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Medical illnesses and diseases are rampant across the world. With new strains of diseases like the influenza, the coronavirus and existing maladies like HIV/AIDS and others, pharmaceutical companies and research labs are striving towards working towards finding medicines and other cures. Compounds or medicines that may exert a direct physiological effect on animals, plants, or microorganisms are called Biologically Active Compounds (BACs). Compounds like vitamins, antibiotics, and insecticides are all BACs as they have direct physiological effects on living beings. BACs have a great importance in the healthcare and pharmaceutical industries as they have a diverse range of effects in the human body and can be used to regulate biological processes for instance, antioxidant properties of some BACs. BACs are complex structures created from organic molecules, which are generally any chemical compounds that contain carbon. 1 Organic chemistry is the study of the properties, synthesis, reactions of these organic compounds. Dr. Sidney Wilkerson-Hill, Assistant Professor in the Department of Chemistry at the University of North Carolina at Chapel Hill, is leading the synthesis of these Biologically Active Compounds as they aid in the synthesis of natural products to be used in medicines. As a pioneering researcher in organic chemistry, Dr. Hill’s lab focuses on three main processes. The first is the development of new chemical reactions and their reaction methodology. 1 These are critical for advances in different sectors like pharmaceutical, biological, and material. The main idea behind these reactions is access to chemical space. 1 This is a concept which refers to the property of space that belongs to molecules which are defined by principles of boundary conditions in a chemical compound. Cycloaddition reactions are especially important because they allow a rapid increase in this chemical space due to their complexity. 1 Cycloaddition reactions are specific chemical reactions used in organic chemistry which basically
Dr. Sidney Wilkerson-Hill Figure 1: Glycosmis stenocarpaand Murraya koenigii. Two different shrubs found throughout Asia from which dimers are obtained. Image Courtesy of Dr. Sidney Wilkerson-Hill.
have a cyclic or circular structure to them. The Hill Lab focuses on developing cycloaddition reactions which have such a relative spatial arrangement of atoms. Natural Products which have been isolated from natural sources like bacteria, plants, and marine sponges often have important biological function. For instance, the Biologically Active Compounds can be used in anti-HIV or anticancer drugs. 1 These compounds are thus very useful for developing new drugs and pharmaceuticals. These compounds can also be used to understand biologically retroactively by studying the effects of the molecular drugs and their reactivity in the complex chemical environments. 1 That’s why the use of natural products to understand complex biology is a major aspect of Dr. Hill’s Lab. Complex natural products can be obtained by the synthesis of a sequence of reactions and this is the third main goal of the Hill Lab. 1 Strategies to make these synthetic products can help fuel innovative reaction processes. This can help uncover the new reactivity of small molecules which can also help replace the use of natural products which may be lesser in quantities that are used for particular drugs. 1 The total synthesis of this product also refers to how the structure of these products can be deciphered in order to understand how they function. The Hill Lab uses these organic compounds and cycloaddition reactions to understand how these natural products’ functions relate to their structure. 1 Dr. Hill’s passion for chemistry originated in a
high school Science Olympiad he was compelled to be a part of. From there he went on to study at NC State and majored in chemistry and textiles and then went to graduate school at UC Berkeley. After completing his postdoctoral studies at Emory University, he joined UNC-Chapel Hill. One of the main aspects of Dr. Hill’s research is using new reactions to create dimeric compounds. 2 Dimers are compounds that consist of two identical monomeric molecules. Using a sequence of events, for instance like two separate pathways, a product can be formed by completing two steps at once. 2 Dimers have unique dimerization patterns and other characteristic features. Dimers also have unique stereochemistry, or chemical orientations and spatial arrangements. They have various sources but some of them are obtained from small shrubs like Glycosmis stenocarpa and Murraya koenigii which are found throughout Asia (Figure 1). Symmetric dimers can also undergo a process known as desymmetrization to form a nonsymmetric dimer. One of the most interesting compounds Dr. Hill worked on during his Postdoctoral studies were called Dihydroindoles. 2 Indoles are important motifs found in Chemistry. In nature, they are found in amino acids, the compounds that make up proteins. For instance, it is the amino acid, Tryptophan that is present in turkey that makes you sleepy after a Thanksgiving meal! 1 Using these Dihydroindoles, biological reactions can be used to incorporate them into synthetic products. One of the key methods used in this research paper was the NMR, or the Nuclear Magnetic Resonance. 2 This is a common method used to assess the structure of a compound. By configuring the structure, it can be understood how this compound carries out its reactions. The NMR is basically an MRI for chemical compounds. Different organic groups called functional groups have different signature data. This paper focused on the synthesis of these Dihydraindoles using specific synthesis mechanisms and their structures. 2 Using this research Dr. Hill is continuing his research using this knowledge to make structures based on the knowledge of the synthesis of these Dihydroindoles. 2 Dr. Hill’s Lab is working on making Biologically Active Compounds that contain different organic functional groups which can possibly be used to synthesize different drugs. Through his recent research paper, Dr. Hill’s main focus was observing how certain structures relate to the speeds of certain catalyst reactions. 1 This study focused on trying to understand the kinetics, which is measuring and studying the rate of a chemical reaction, of a cyclic compound and using this data to try and develop conditions for how the reaction can proceed even with a smaller amount of the catalyst being used in the reaction. 3 A catalyst is a substance that enhances the rate of a chemical reaction without itself undergoing any change chemically. This paper helped understand the kinetics of the reaction based on a variety of catalysts. 3 This information can further help us understand how fast a product can be obtained based on the variety of catalysts that are used. In his study, Dr. Hill used Dirhodium catalysts due to their versatile catalyst nature, including transformations that involved cyclic compounds (Figure 2). 3 Dr. Hill aims to use all this to develop the basis of his research at UNC-Chapel Hill. He wants to create these synthetic molecules using natural products by understanding the underlying chemistry behind it. 1 With his expertise in the organic chemistry field and his passion for fostering curiosity and an appreciation for science, Dr. Hill continues to lead ground-breaking research and exert a positive force in his research.
References
1. Interview with Dr. Sidney Wilkerson-Hill, March 11, 2020. 2. Wilkerson-Hill, S. M.; Haines, B. E.; Musaev, D. G.; Davies, H. M. L. “Synthesis of [3a,7a]-Dihydroindoles by a Tandem Arene Cyclopropanation/[3,5]-Sigmatropic Rearrangement Reaction” 3. Wei, B.; Sharland, J. C.; Lin, P.; Wilkerson-Hill, S. M.; Fullilove, F. A.; McKinnon, S.; Blackmond, D. G.; Davies, H. M. L. “In Situ Kinetic Studies of Rh(II)-Catalyzed Asymmetric Cyclopropanation with Low Catalyst Loadings”
