Structurally complex terpenoid compounds provide access to a wide assortment of potential biological functions that can be exploited to develop pharmaceutical therapies. Despite recent efforts to increase efficiency within the pharmaceutical research and development sector, drug discovery is still an extensive, costly, and inefficient process, which maintains a low rate of new therapeutic discovery. Approximately one in every 5,000 compounds that reach the preclinical testing stage becomes an approved drug in the United States, and costs average nearly $2.6 billion to develop a drug over a 10-year period. The systems in place for drug discovery and design are in need of increased efficiency, which could be achieved through systematic production of chemical compounds for initial testing phases. Researchers at the University of Florida have developed a simple and scalable strategy to synthesize diverse arrays of compounds containing polycyclic terpene cores, which increases drug discovery efficiency and simplifies early-stage development of therapeutic agents. This uncomplicated approach uses inexpensive and abundantly available reagents, lowering costs associated with ongoing drug discovery and design efforts throughout the pharmaceutical industry.
Systematic synthesis of terpenoid compounds for drug design and development.
This synthesis strategy uses inexpensive and abundantly available Knoevenagel adducts (cycloalkanones + malonitrile) and allylic electrophiles to systematically generate a diverse array of terpenoid natural product scaffolds with wide-ranging potential biological activities. The process uses three known chemical reactions, allowing the user to manipulate functional groups present on the final polycycloalkane compounds. The strategy is highly tunable, encouraging development of complex molecular structures with a high yield and without need for extensive optimization. This increase in molecular malleability will enable countless drug discovery and development efforts.