Towards antifungal compounds : total synthesis of jerangolid D

The main thrust of this Thesis is focused on the total synthesis of (+)-ambruticin. It was envisioned that our strategy, leading towards to this molecule, will be short, efficient and highly versatile. Therefore, novel methodologies which would enable us to construct complex molecules starting from three or more fragments (multicomponent reactions) or novel C-C bond forming reactions, leading to the stereoselective formation of polysubstituted olefinic structures, were searched. To answer these challenges, two novel methodologies were developed. First among them, a multicomponent Sakurai reaction, based upon the chemistry of silicon, gave us a short and efficient access to dihydropyran subunits. The second methodology, which involves the chemistry of sulfur, is a modification of the classical Julia olefination method. However, it enables us to achieve the synthesis of tri- and tetrasubstituted olefins with high stereocontrol. The scope and limitations of these methods were studied in details. Additionally, the applicability of these methods was tested in the context of other natural products synthesis, leading to a short and efficient preparation of (+)-goniothalamin, (+)-goniothalamin oxide, (+)-kavain and jerangolid D. Finally, we have decided to apply our silicon and sulfur-based methodologies to a connective total synthesis of (-)-dactylolide, which is itself a potent cytotoxic molecule. More interestingly, it is also a direct precursor (one step) to another natural product, (-)-zampanolide. This molecule is known for its high cytotoxic activity (~2ng/mL). Unfortunately, it is not available in sufficient amount for in depth biological studies.