The main objective of Action D28 was the target-orientated discovery of new natural products with an important biological profile based on new and unusual sources, e.g., secondary metabolites of bacteria or marine organisms combined with efforts to synthesise these molecules by the use of novel strategies and methods. The development of new strategies to synthesise complex natural products was the second main objective. This was to enable a broad screening of analogues with the possibility of using structure-activity data to further refine the pharmacophore model, thus allowing for the rational design and synthesis of more focused active compounds. The main achievements of this Action can be summarized as follows:
- Several lichen metabolites in suitable amounts have been obtained to be tested on various cancer cell lines and as radical scavengers. Additionally, new lichen compounds have been characterised in minute amounts in several species. Some synthetic compounds, mainly obtained through solid support or fluorous phase synthesis, have also been tested.
- The synthesis of a series of iminosugars bearing two or three alkyl chains and aimed at the treatment of Gaucher disease, the most common of the lysosomal disorders, were designed as ceramide mimics and analogs of N-butyl 1-deoxynojirimycin (Zavesca®).
- The development of synthetic methods, such as enantioselective synthesis, desymmetrisation of dienes, carboazidation processes, acyliminium ion chemistry, metathesis, and C-H bond activation has played a central role in the synthesis of several different families of alkaloids chosen according to their biological activities.
- New pyrazolo-heterocyclic systems via Pd-mediated intramolecular coupling, the formation of piperidine derivatives, quinolines and diazepines, and the synthesis of pyrrolidinones have been achieved.
- The development of new methods for the enantioselective synthesis of piperidine-containing compounds starting from chiral bicyclic lactams have allowed the synthesis of a large variety of simple piperidines, benzo[a]quinolizidines, indolo[2,3-a]quinolizidines and spiroindolines.
- The synthesis of new tubulin binding epothilone analogues and their biological testing in the context of new anticancer active agents. Action D28 coordinated the work of scientific teams from 23 countries. The achievements of this Action have been disseminated through various Action-organised workshops and Working Group meetings, the organisation of a Training School, presentations at various international conferences, and the publication of many research articles in peer-reviewed journals.
