Natural history, bio-inspiration and natural product synthesis: chemistries in a museum

Natural products are used by living organisms to communicate or compete and are originated from genetically encoded pathways responding to biotic or abiotic environmental stimuli. Consequently they may have extremely diverse biological properties, with useful medicinal, agrochemical and other applications. It is the purpose of our work to study the molecular origin, the chemical reactivity and the biological role of such compounds at the National Museum of Natural History [1]. This should ultimately lead us to biomimetic synthetic adventures aiming at understanding how complex natural products can be made by living organisms [2]. This presentation will give a snapshot of selected examples whose choice will be driven by the observation of Nature, structure analysis and reactivity studies of fungal natural products. Special attention will be paid to the total synthesis of hybrid polyketides in the chalasan and related series (fungal PKS-NRPS biosynthetic pathways, Figure) [3]. We will concentrate on the use of key biomimetic intermediates to demonstrate how structural complexity can be installed in polycyclic natural products, in connection with natural product isolation and biosynthetic experiments [4,5].

Acknowledgements: We are grateful to the CNRS, MNHN and the National Research Agency (ANR: Synbiorg project N°ANR-12-BS07 – 0028 – 01) for funding this work.

Keywords: Biomimetic synthesis, total synthesis, chemical reactivity, fungal metabolites.

References:

[1] Prado S, Li Y, Nay B. Diversity and ecological significance of fungal endophyte natural products. In Rahman A, editor. Studies in Natural Product Chemistry, vol. 36. Amsterdam: Elsevier Science; 2012: 249 – 296

[2] Poupon E, Nay B, editors. Biomimetic Organic Synthesis. Weinheim: Wiley-VCH; 2011.

[3] Li XW, Ear A, Nay B. Hirsutellones and beyond: figuring out the biological and synthetic logics toward chemical complexity in fungal PKS-NRPS compounds. Nat Prod Rep 2013; 30: 765 – 782

[4] Li XW, Ear A, Roger L, Riache N, Deville A, Nay B. Bio-inspired formal synthesis of hirsutellones A-C featuring an electrophilic cyclization triggered by remote lewis acid-activation. Chem. Eur. J. 2013; 19: 16389 – 16393

[5] Ear A, Amand S, Bianchard F, Blond A, Dubost L, Buisson D, Nay B. Direct biosynthetic cyclization of a distorted paracyclophane highlighted by double isotopic labelling of L-tyrosine. Org Biomol Chem 2015; 13: 3662 – 3666