Professor M. Cristina White has developed iron-based small molecule catalysts which, in conjunction with hydrogen peroxide, can selectively oxidize aliphatic C-H...
Professor M. Cristina White has developed iron-based small molecule catalysts which, in conjunction with hydrogen peroxide, can selectively oxidize aliphatic C-H bonds in complex natural products.
Organic synthetic strategies are typically designed around the use of protecting or activating groups to yield desired products. While the use of these types of groups is well developed and widely used, this approach often generates waste and introduces unwanted complexity into the synthetic sequence. Methods which allow introduction of functionalities without activating or protecting groups can significantly impact synthetic methods. In particular, reactions which can predictively and selectively oxidize isolated, unactivated sp3 C-H bonds in complex substrates are of particular value as they enable introduction of functionalities in the later stages of synthetic sequences.
White has developed catalyst systems which achieve this oxidation of C-H bonds based solely on electronic and steric properties of the bond. With the additional use of carboxylate directing groups, diastereoselective lactonizations can be achieved.
A compelling example of the selective oxidation of a C-H bond is the conversion of the antimalarial compound artemisinin which contains five potential C-H sites for oxidation and a cleavage-sensitive peroxide functional group[1]. Using White's iron-based catalyst and its designed selectivity, the targeted C-H bond is oxidized preferentially to give the desired product in higher yields, with shorter reaction times, and in higher volume throughputs compared to enzymatic reactions.
White's catalyst systems open powerful methods to greatly streamline synthetic methods by offering predictive and selective aliphatic C-H oxidation in complex substrates.
Applications
Pharmaceuticals
Specialty Chemicals
Benefits
Predictive and selective oxidation of C-H bonds in complex systems
Preparatively high yields and rapid reaction rates
Elimination of need for activating and protecting groups
Utilization of inexpensive and environmentally friendly oxidant, H202
Enabling of late-stage introduction of oxidized functionalities
Dr. John Katzenellenbogen from the University of Illinois has designed Pathway preferential estrogens (PaPEs) that are novel synthetic compounds that...
Dr. John Katzenellenbogen from the University of Illinois has designed Pathway preferential estrogens (PaPEs) that are novel synthetic compounds that structurally resemble the natural estrogen but with its reduced binding affinity, form ER-PaPE complex with a short lifetime of seconds. This short binding is sufficient to selectively activate the ER non-genomic pathway and not the ER genomic pathway. PaPEs are shown in animal models to promote health of metabolic tissues and vasculature; reduces body weight gain and fat accumulation after ovariectomy and accelerates repair of endothelial damage; no stimulation on breast and endometrial cancerous cells.
Technology Benefits: • Selectively activates ER non-genomic pathway • Results in an enhancement of the repair of vascular injury, & prevents weight gain • No stimulation on breast and endometrial cancerous cells
Dr. White from the University of IL has developed a small molecule catalyst which enables the chemoselective methylene hydroxylation in aromatic systems. This...
Dr. White from the University of IL has developed a small molecule catalyst which enables the chemoselective methylene hydroxylation in aromatic systems. This modification is highly desired in small molecule therapeutics, natural product and natural product derivatives synthesis.
Dr. Denmark from the University of IL has developed a computer-assisted workflow for catalyst design and reaction outcome prediction. This workflow significantly shortened screening process for organic synthesis and has great potential in pharmaceutical research and development.
Publications – Zahrt et al., Science, 363, eaau5631, 2019.
Macrocyclic peptide natural products are highly valued for their potent antibacterial, antifungal, antiviral, anticancer, and immunosuppressive activities. They possess...
Macrocyclic peptide natural products are highly valued for their potent antibacterial, antifungal, antiviral, anticancer, and immunosuppressive activities. They possess desirable properties such as proteolytic stability, increased cell-membrane permeability, and conformational restrictions, making them attractive for therapeutic applications. Ribosomally synthesized and post-translationally modified peptides (RiPPs) often have macrocyclic structures, with biosynthesis involving gene-encoded precursor peptides modified by enzymes in a biosynthetic gene cluster. Thiopeptides, a type of macrocyclic RiPP, are known for inhibiting bacterial protein translation. However, creating thiopeptide derivatives with multiple variations is challenging.
This technology is a method for biosynthesis of novel pyritides thiopeptides, pyridine-based macrocyclic peptides. Pyritides may be useful for targeting pathogens and diseases that cannot be targeted with small molecules. The steps in the process constrain the peptides allowing modifications of the inner ring without interfering with the reaction.
Publication
Accessing Diverse Pyridine-Based Macrocyclic Peptides by a Two-Site Recognition Pathway
