Natural Products and Their Mimics as Targets of Opportunity for Discovery

Abstract

Diverse structural types of natural products and their mimics have served as targets of opportunity in our laboratory to inspire the discovery and development of new methods and strategies to assemble polyfunctional and polycyclic molecular architectures. Furthermore, our efforts toward identifying novel compounds having useful biological properties led to the creation of new targets, many of which posed synthetic challenges that required the invention of new methodology. In this Perspective, selected examples of how we have exploited a diverse range of natural products and their mimics to create, explore, and solve a variety of problems in chemistry and biology will be discussed. The journey was not without its twists and turns, but the unexpected often led to new revelations and insights. Indeed, in our recent excursion into applications of synthetic organic chemistry to neuroscience, avoiding the more-traveled paths was richly rewarding.

Antimicrobial Effect and Antioxidant Activity of Triterpenes Isolated from Gymnema sylvestre R. Br.

“…Today it is known that plants are a precious reservoir of secondary metabolites with low molecular weight [17][18][19], belonging to numerous classes of substances [3][4][5] and used for the defense against insects, microorganisms or even from other plants [9][10][11][12][13]. Over the years, there was a continuous and ever increasing request of new natural substances that are commonly considered nontoxic and safer than synthetic ones [20][21]. Considering that one of the most serious health threats is the antimicrobial resistance (AMR) [22], recently, there was an increasing interest in natural extracts or their single components endowed with antimicrobial activity.…”

Beyond Pseudo‐natural Products: Sequential Ugi/Pictet‐Spengler Reactions Leading to Steroidal Pyrazinoisoquinolines That Trigger Caspase‐Independent Death in HepG2 Cells

“…Fortunately, the new chemoinformatic tools developed for mining the information encompassed in the rapidly growing chemical databases have shed some light on understanding the main structural features in NPs that seem to confer them a higher biological relevance [8,11–13] . In this sense, several approaches have been proposed for designing new compounds known as NP mimics , synthetic molecules that, although not direct analogs of a particular NP, are enriched in the structural features of NPs [14–18] . Some of these approaches employ a strategy that incorporates scaffolds already present on NPs into the design process.…”

Antitubercular and antibacterial activities of isoxazolines derived from natural products: Isoxazolines as inhibitors of Mycobacterium tuberculosis InhA

“…8,10 Chemical transformations involving the use of natural products as starting materials have been extensively applied in the fields of natural product research and medicinal chemistry. 11,12 Such transformations entail the use of natural products as building blocks, and the resulting natural product derivatives exhibit enhanced biological activities, thus leading to the discovery of new drug candidates. In nature, various natural products contain terminal alkene moieties, with some being reported to have antitubercular activities.…”