Synthesis of HuaCat® Analogues as Novel Organocatalysts for the Formation of Asymmetric C-C Bonds
The synthesis of organic compounds with preferential stereochemistry is ubiquitous in the scientific community. A chemical reaction that asymmetrically induces one stereoisomer over another is achieved through the use of catalysts and various coupling reagents.1 Inorganic catalysts, such as TiCl4 and ZnCl2, have been documented for many decades as effective agents in the synthesis of asymmetric bonds, however, there are environmental limitations to their use. First, the asymmetric reactions involving these metal catalysts require solvents that are not environmentally-friendly, especially when used on an industrial scale and second, the metal catalysts are recycled when possible, however, there is always metal waste that is equally unfriendly to the environment. One solution is to develop organocatalysts (non-metal catalyst) that will accomplish the same asymmetric reactions in aqueous reaction conditions. HuaCat® and HuaCatII® are organocatalysts developed by Dr. Rich Carter at Oregon State University that are able to achieve a single stereochemistry in 98% yield with greater than 95% diastereomeric excess.2, 3 These catalyst are not metal-containing and do work in aqueous conditions, but they still require the use of some solvent. The development of analogues of HuaCat® by substituting aromatic substituents with different electron withdrawing/donating groups will afford catalysts with increased yield and more predictable stereochemistry in aqueous conditions. One of the major challenges of the project is the formation of the key peptide bond of an amino acid and a sulfonamide containing a highly electronegative aromatic substituent in the ortho position, a feat that has minimal (and questionable) literature support to date. In this paper, we will detail the methods that have been attempted and the future plans for overcoming this unfavorable reaction to achieve what could be a new path to a unique organic structure for further synthetic manipulation.
Biochemistry, Biophysics, and Structural Biology, Life Sciences, Medicinal and Pharmaceutical Chemistry, Biochemistry; Chemistry - Organic; Catalysts, Asymmetric reactions; Assymetric bonds; Organocatalysts
Networked Digital Library of Theses and Dissertations