Chalcitrine and sclerocitrine: how nature can produce chemical diversity? – X-comic

To elucidate biosynthetic routes two complementary approaches are simultaneously evaluated: i) a total synthesis following a complete biomimetic approach; ii) the identification of biosynthetic intermediates from the producing organisms. For the total synthesis a fully biomimetic approach was chosen both to accomplish a straightforward synthesis of complex molecules in a very limited number of steps and to validate the reactivity of the intermediates. A biomimetic synthesis also furnishes never described intermediates but involved in biosynthetic routes. For the isolation part of the project, mushrooms were collected, and the comparison of molecules isolated to the ones obtained from the synthesis part of the project allows to validate the biosynthetic hypothesis and to isolate new metabolites from ecological interest.

Concerning the total synthesis part of the project a straightforward synthesis in six steps of the constituting monomer was developed. The choice of a fully biomimetic approach associated to selective method for the introduction of the substituents delivered a competitive synthesis. Based on this synthesis, the study of the biomimetic assemblies can be performed. For the isolation part of the project, sample collection of kilograms of mushrooms allowed the production of a crude extract. Valorizing the molecular network approach based on MS-MS fragmentation new dimers were identified and will be priority isolated.

Mains focus of the project will be now to realize a complete biomimetic assembly study to achieve total syntheses of chalcitrine and sclerocitrin. Complementary to the isolation of natural products from mushrooms it will allow to identify a rational biosynthetic scheme.

Results will be published in due course.

Nature is able to assemble simple chemical building blocks and increment structural complexity to produce highly refined natural products. In this context, chalcitrin and sclerocitrin, two pigments displaying highly complex molecular structures isolated from common mushroom represent ambitious synthetic targets. Biosynthetic hypothesis has been emitted for their origin based on the condensation of an oxidized form of xerocomic acid and involving a complex cascade of skeletal reorganization. The overall objective of this project is to develop a synthesis of the highly intricate frameworks of sclerocitrine and chalcitrine based on a full biomimetic strategy. Considering a straightforward access to xerocomic acid, the biomimetic assembly will be a central task of the project. This proposal of fundamental organic chemistry got the aim of synthesize highly complex molecule, and to afford a better understanding of their biosynthesis and their ecological significance. In the context of chemical ecology, identify biosynthetic intermediates and new scaffolds from mushrooms extracts. This project at the interface of biosynthesis, biomimetic total synthesis and identification of natural products will be conducted by the BioCIS team (Coordinator: L. Evanno, faculty of Pharmacy) at Université Paris-Sud.