Total synthesis for integrated chemistry and biology

WP4: Synthetic natural products and their applications

The complexity of natural products have always been recognized as an important driving force for the development of organic chemistry by stimulating chemist’s creativity. It pushes synthetic chemists to discover new reactions and new strategies for their production. In addition, today, sustainable approaches in organic synthesis are also important to be considered for scalability. As discussed with other WPs, inspiration may come from the knowledge of biosynthetic pathways[1] and may grow from structural analyses. Programs on the total synthesis of natural products isolated in i-NPChem groups and holding interesting biological properties may be prioritized in i-NPChem. Alternatives combining biological and chemical synthetic approaches (the BIO-CHEM/CHEM-BIO methodologies)[2] could be utilized: fermentation processes indeed produce compounds that can be further functionalized by synthetic means, while the use of synthetically modified precursors in fermentation processes can lead to natural product analogues produced in vivo. In any case, organic synthesis, along with biotechnology for compound production, is the closest way to applied developments towards useful products discussed in WP6.

Example of synthetic material showing respiratory chain inhibition on cancer cells © Bastien Nay[3]

The connections of total synthesis with chemical biology have become evident with the discovery that natural products and functionalized derivatives can be used as tool for the study of biological processes at the molecular level. Combined with the availability of large natural product based libraries, biological screenings have uncovered biologically active compounds that can be used in cellular and molecular biology, for example to study in cell protein trafficking. The possibility to functionalize biologically relevant compounds with fluorescent or any other probe allows the study of biological mechanisms of action. As for isotopic labelling for metabolic studies, organic synthesis is essential. Like chemical biology which has finds useful biomedical applications, chemical ecology may benefit a lot from such tools with useful agrochemical applications.

Example of synthetic pigments (left) originally found in a myxomycete (right) © Bastien Nay[4]

[1] E. Poupon and B. Nay (Eds) Biomimetic Organic Synthesis (2011), Wiley-VCH: Weinheim.

[2] A. Kirschning, F. Hahn, Angew. Chem. Int. Ed. 2012, 51, 4012-4022.

[3] X.-W. Li, J. Herrmann, Y. Zang, P. Grellier, S. Prado, R. Müller, B. Nay, Beilstein J. Org. Chem. 2013 (special issue: Synthesis and Biosynthesis), 9, 1551-1558.

[4] N. Riache, C. Bailly, A. Deville, L. Dubost, B. Nay, Eur. J. Org. Chem. 2010, 5402-5408.