Terpenes: from biodiversity to chemical diversity and bioactivity

Terpenes are a class of naturally occurring compounds widely distributed in both animal and plant kingdoms; these products have historically played a crucial role in drug discovery due to their ability to alter different biochemical processes. Nowadays, terpenes are still used as pharmaceuticals, such as the anticancer drug paclitaxel or their semisynthetic derivatives like the anti-inflammatory agent bardoxolone methyl. However, natural compounds present two main limitations: the first one is the limited availability of certain compounds from their natural sources, which complicates their extraction and supply. The second one is linked to the decreasing discovery of novel and unique scaffolds, which are essential for uncovering new bioactivities and advancing drug discovery. The aim of this PhD program was to investigate the chemical reactivity of specific terpene classes by increasing the complexity of their carbon skeletons, with the goal of discovering new bioactivities or enhancing existing ones. In particular, the thesis will be divided into two main chapters: the first will focus on skeletal editing, addressing new rearrangements of the Tigilanol Tiglate molecule, and the second will deal with the construction of a new library of compounds called terpen curcuminoids. The second chapter will concentrate on the skeletal interconversion of triterpene classes through a semisynthetic approach, which includes the use of photochemistry to promote key rearrangements. All compounds obtained in the reported projects have been subjected to biological testing.