Tigliane diterpenoids: isolation, chemistry and preliminary biosynthetic studies of a medicinal relevant class of natural compounds

Tiglianes are a class of polycyclic diterpenoids, densely functionalized, isolated from Euphorbiaceae and Thymelaceae family. Despite their extensive use in biomedical research, and their potent and unique biological profile, phorboids are still largely unexplored in terms of chemistry, biosynthetic origin, and mechanisms of activity. This thesis aims at providing a contribution en route to the clarification of these issues. Part la describes an expeditious isolation method of the parent diterpene polyol phorbol from croton oil (Croton tiglium L. oil), and of the basic diterpenoid skeleton of tigilanol tiglate from left-overs from the isolation of this compound from the seeds of Fontainea picrosperma C.T.White. Part Ib presents SAR studies aimed at the exploration of the chemical space of tiglianes, and an exploration of their chemical reactivity. Part II presents a biosynthetic investigation on the origin of the tigliane skeleton, inspired by the Jakupovic proposal of non lathyrane derivation of these compounds. The synthesis of labelled precursors is presented as well as a series of feeding experiments on Fontainea picrosperma.