Asymmetric Synthesis of Pharmacologically Active Compounds by Using Asymmetric Allylations and Ring-Closing Metathesis

The objective of this Ph.D. Thesis is the synthesis of several natural lactones that can be classified into three groups, according to their ring size: small-sized (hyptolide, synargentolide A and passifloricin A), medium-sized (microcarpalide and lethaloxin) and large-sized (FD-891). Furthermore, gustastatin has been synthesized by means of photochemical esterification, showing the increasing utility of this new methodology developed by De Brabander and co. All the procedures have been carried out with high enantio and regioselectivities employing a wide range of the newest asymmetric methodologies. In this way, the main targets that have been achieved are: (a) the initial structure, elucidated by means of spectroscopic and physical data (hyptolide, microcarpalide, gustastatin and FD-891) has been checked; (b) the initial connectivity in synargentolide A has been proved to be wrong, and it has been corrected in the case of passifloricin A; (c) previous contradictions in lethaloxin have been clarified. At the same time, several non-natural isomers thereof have also been synthesized by means of minor modifications in the initial synthesis pathway. These non-natural derivatives may be potentially useful for structure-activity studies. These have already provided successfully results in some cases and areunder development in other ones.