Infusing the Undergraduate Curriculum with Medicinal Chemistry Techniques Using Real-World Examples Involving Bioassay-Directed Synthesis of Chalcone-based Citrus Fruit Bioregulators

1-phenyl-3-(p-diethylaminoethoxyphenyl)-2-propen-1-one, a chalcone-based bioregulator, was synthesized through a two-step process involving Claisen-Schmidt condensation of benzaldehyde and acetophenone followed by nucleophilic substitution with diethylaminoethyl chloride hydrochloride. The bioregulator induced significant production of lycopene in citrus fruits (i.e., oranges and lemons). The intermediate chalcone phenoxide anion as well as chalcone, ergosterol, and cholesterol were less effective compared to the bioregulator. Lycopene has been the focus of many studies because of its anti-prostate cancer and anti-oxidant properties. Our bioassays were straightforward. Citrus fruits were coated with bioregulators and placed near a window to allow carotogenesis to occur within seven days. A thin layer of citrus fruit peel was removed using a grater then extracted with n-hexane. The amount of lycopene in n-hexane was determined using UV absorption spectroscopy. Chalcone-based bioregulators were chosen for the model medicinal organic chemistry experiment because chalcones are real chemical estates that easily lend themselves to robust multidisciplinary research opportunities such as integrating the world’s best synthetic methods developed by Nobel Laureates (e.g., Diels-Alder, Smalley, and Corey), nanomaterials, and green chemistry into undergraduate curriculum. The proposed experiments were carefully designed so that they match the skill levels of students at two- and four-year colleges. Our ongoing US-Africa medicinal project focuses on hypothesis-driven guided inquiry synthesis of novel chalcone-based citrus bioregulators. The goal is to optimize the activity of enantiomers of bioregulators. Since the individual enantiomers may vary in biological activities, their bioregulatory profile will provide important information needed to understand possible physiological effects on citrus fruits.