Enantioselective, organocatalytic synthesis of the secoiridoid natural product Patriridosid D and evaluation of its potential as an antitumoral agent

• Applicant: Professor Dr. Matthias Breuning
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation ; Biological and Biomimetic Chemistry
• Term: from 2015 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 290523566

Modern natural product and drug synthesis combines synthetic-methodical questions (synthetic economy; highly specific and stereoselective transformations; balancing of reactivities) with structural-aesthetic aspects (highly functionalized molecules; novel architectures) and medical-chemical topics (action profile; search, optimization, and simplification of lead structures). The project applied for comprises many of these aspects. Primary goal is the efficient, enantioselective, and first total synthesis of the natural product Patriridosid D, which possesses a novel secoiridoid skeleton with four consecutive stereogenic centres. Based on our preliminary work, up-to-date, environmentally friendly organocatalytic transformations will be used as the key steps on densely functionalized intermediates, e.g. on a trialdehyde species, which also exists in similar form in nature. The natural product Patriridosid D was isolated from the perennial herb Patrinia Scabra Bunge, the extracts of which were applied in traditional Chinese medicine for treatment of leukaemia and gastric cancer, and it shows a specific cytotoxicity against the cisplatin resistant gastric cancer cell line MKN-45. Further goals are therefore the evaluation of its action profile against different types of cancer and the synthesis of derivatives for structure-activity studies and for improving the specific antitumoral activity.If the proposed project is successful, new synthetic knowledge will be gained and a novel, easily accessible lead structure for a potential anti-cancer drug will be obtained.

• DFG Programme: Research Grants
• Cooperation Partner: Professor Dr. Rainer Schobert