Solution- and solid-phase synthesis of novel heterocycles via high-pressure promoted cycloadditions of nitroalkenes : an entry towards structural diversity

Abstract

Medicinal chemists are continuously trying to design new and more effective drugs. In particular drugs that show (almost) no side effects. A new method is developped for the synthesis of so called compound libraries of novel potential drugs to gain more insight in the relation between molecular structure and (side)effects. It is shown that the synthetic method can be used in combinatorial chemistry and easily be automated in order to produce rapidly many novel potential drugs. Another important aspect of the method is the application of very high pressures (upto 15,000 atmosphere) that allow the generation of a great number of unique compounds via domino cycloaddition reactions. The compounds described in this thesis are closely related to the neurotransmitters dopamine and serotonine, which play a role in psychic disorders such as schizophrenia, (manic) depressions and also Alzheimers and Parkinson's disease