Cette thèse développe de nouvelles séquences réactionnelles divergentes vers les lactones sesquiterpéniques, ainsi que leurs analogues. La réactivité multiple d’un substrat linéaire face à divers catalyseurs a tout d’abord permis d’obtenir différentes structures polycyliques dont la fonctionnalisation a permis d’isoler plusieurs produits naturels et des analogues. De nouvelles méthodologies ont été étudiées pour accéder aux gamma-butyrolactones, une fonctionnalité prépondérante dans les lactones sesquiterpéniques, ainsi qu’au noyau hydroazulène contenu dans les guaianes. Enfin, une synthèse divergente courte et performante a été mise au point pour accéder à divers analogues de la déoxyéléphantopine, un sesquiterpène aux propriétés anti-cancéreuses, afin de moduler et étudier son activité biologique. En parallèle de ces travaux sur les sesquiterpènes, une autre chimie a été explorée visant à réaliser la glycosylation de cystéines avec des carbohydrates non protégés. / The main thread throughout this thesis is to develop reaction sequences that could provide facile access to the sesquiterpene lactones, or analogs thereof, using strategies that would be compatible with divergent reaction pathways. A first project harnessed the multiple reactivity mode of a linea rsubstrate to obtain different polycyclic frameworks found in sesquiterpenes whose functionalisation led to several natural products and their analogs. New methodologies were studied to access gamma-butyrolactones, a preponderant functionality in sesquiterpene lactones, and hydroazulene core, the bicyclic framework of guaianes. Finally, a short divergent pathway was designed to access diverse analogs of deoxyelephantopin, a sesquiterpene showing anti-cancer effects, so as to modulate and study its biological activity. In parallel to this work on sesquiterpenes, a different chemistry was explored aiming at performing glycosylation of cysteines with unprotected carbohydrates.

The neoclerodane furanoditerpenoid family of natural products is a compelling target for a divergent total synthesis due to the complexity around their spirolactone-containing decalin core, the similarities between their functional groups, and biological activities that indicate a potential for future medicinal application. While being a relatively small molecule, the most structurally complex compound of the family, teucrin A, contains six stereocenters, five of which are contiguous. Our divergent synthesis route involves the stereo-controlled formation of a common decalin intermediate in four concise steps and 32% overall yield from commercially available starting materials. Additionally, desmethyl montanin A - an analog of montanin A missing its methyl group - can be produced from this key intermediate in one step and 95% yield, for a total of 30% yield over five steps. The dual-key step of this route consists of a Lewis acid-catalyzed Diels-Alder cycloaddition which stereo-selectively forms the spirolactone, followed by a gold-catalysed 6-exo-dig cyclization of the Diels-Alder adduct to complete the decalin core. The complementarity of these two steps is the focus of the synthesis, with the remaining steps for the formation of select neoclerodane natural products consisting of simpler classical chemistry, highlighting the potential for the creation of a large "unnatural" product library for applications such as drug candidate screening. Progress has additionally been made toward teucrin A, setting a cornerstone for future advancements to be made on this project. This concise synthesis advocates for the Barriault group's Diels-Alder/gold cyclization method of forming complex structural cores and will be applied to the total syntheses of other natural products in the future.