Synthèse de molécules d’intérêt biologique. Contribution à la synthèse des bastadines

Abstract

Synthesis of molecules of biological interest. Contribution to the synthesis of bastadins. The metabolites are a biochemical area whose interest is in constant progression. Indeed, these molecules are biologically active and are used in therapeutic treatments. This work focuses on the solid phase synthesis of macromolecules from metabolites synthesized by an enzyme. The development of Erwinia herbicola cultures has achieved the synthesis of metabolites: L-dopa and dopamine. From a medical point of view, these molecules have a particular interest since they act as neurotransmitters in human nerve cells. Through a chemical reaction scheme from dopamine, we are interested in solid phase synthesis of a macromolecule like bastadin (bis-diarylethers). This molecule of natural origin is produced by marine sponge, and has anti-angiogenic and antimicrobial properties. A complete scheme of chemical synthesis of bastadines was developed by Couladouros et al. (2005) in homogeneous phase, but it requires a lot of steps with an overall yield of synthesis extremely low (less than 1%). This work aims to develop and implement a part of original scheme for the synthesis of this molecule in heterogeneous phase from dopamine. Indeed the fragment left of the bastadine can be achieved via a coupling reaction in basic medium between dopamine modified on solid support and a diaryliodonium salt