Abstract EN:

Nowadays, the medicinal research takes profit of organic transformations to develop novel synthetic methodologies to afford for example bioactive molecules present in plants. In this manuscript, various facets in organic chemistry have been investigated. The main one was focused on the total synthesis of (2S,3R,4S)-4-Hydroxyisoleucine, a natural product extracted from fenugreek seeds. It is a small amino acid bearing three contiguous stereogenic centers and having some interesting anti-diabetic properties. Two approaches have been designed and successfully validated. The first one is a racemic approach and afforded the (2S,3R,4S)-4-Hydroxyisoleucine and its isomers. It involves a catalytic diastereoselective hydrogenation reaction of an -iminoester precursor. The second strategy aims at developing an industrial scale synthesis of the optically pure natural compound. It is based on the catalytic asymmetric Mannich-Type condensation reaction and the diastereoselective reduction of an N-Protected--keto--aminoester to afford in a four-step synthesis the (2S,3R,4S)-4-Hydroxyisoleucine with a good overall yield and the use of available and cheap starting materials. This synthetic approach also allowed the synthesis of 4-Hydroxyisoleucine’s analogues and their potential anti-diabetic properties are at the moment evaluated in Canada. Besides this project, I studied a regiospecific synthesis of isoxazoles starting from ,-diketonic esters and I examined the use of Rhodium and Ruthenium organometallic complexes in catalytic asymmetric regiospecific hydrogenation of ,-disubstituted-(acetamido)acrylates. I have also worked on the selective deprotection of the para-methoxyphenyl group through anodic oxidation. This electrochemical route can afford primary amine derivatives and constitutes an alternative to the use of classical and environmental unfriendly oxidants such as CAN.