CE07 - Chimie moléculaire

ASymMetric photocAtalySis with DNA-based bio-Hybrids – SMASH

Submission summary

Advances in chemistry over the past century have led to the development of new materials and molecules that have profoundly changed our daily lives. However, the scarcity of oil resources is forcing us to reconsider the way we obtain these molecules, which have become indispensable, and to respond to new issues. It is essential for modern chemistry to be more precise, efficient and eco-compatible. Selectivity, and more particularly enantioselectivity, is a major factor in the synthesis of biologically active molecules. To achieve this, the use of chiral organometallic catalysts has long been the alpha and omega of asymmetric catalysis. However, although very efficient, these catalysts cannot compete with natural enzymes for obtaining chiral centers. Indeed, the latter possess, thanks to their large chiral three-dimensional structure, a high recognition capacity, allowing an optimal positioning of the substrates in favour of the catalyzed reaction. Efficient and selective enzymatic catalysis also allows to work in mild and eco-friendly conditions. However, there are reactions that are not catalysed by natural enzymes. Recently, the concept of biocatalysis has evolved to incorporate DNA. Indeed, within a decade, the double helix of DNA has been used to catalyze a number of reactions in a highly enantioselective manner. Exploiting the fascinating helical structure of DNA and RNA to develop new chiral bio-hybrid catalysts capable of promoting highly stereoselective transformations under mild and eco-compatible conditions is at the heart of this research project.

Initially inspired by natural photosynthesis, photocatalytic reactions have expanded rapidly during the last decades. While, “classical” photochemistry was using ultraviolet light for the direct excitation of organic molecules and remained in the hands of specialists, the demonstration that visible light and photoredox catalysts could be applied to a large range of important asymmetric transformations popularized its use among organic chemists. Although the number of synthetic applications of photocatalysis with visible light is already very impressive, the possibilities for future developments in photocatalysis are overwhelming. In the past few years, our consortium along with several international research groups reported a number of highly enantioselective DNA-based transformations. Our goal in the present proposal is to extend the concept of DNA-based asymmetric catalysis to DNA-based Asymmetric Photocatalysis by developing new and highly selective DNA-based synthetic tools with applications in various asymmetric photocatalytic reactions. More specifically, the project aims at 1) establishing a proof of concept in which DNA is used as a chiral inductor in asymmetric visible light-mediated transformations in water [WP1], 2) rationalize the chirality transfer induced by DNA through a careful design of DNA/photocatalyst systems [WP1 & WP2], 3) develop sustainable catalysts based on recyclable, solid-supported, modified oligonucleotides which will ultimately be implemented to large scale continuous flow processes [WP3] and 4) applying all these tools to the synthesis of structurally intriguing natural products that exhibit interesting biological properties [WP4]. To maximize our chances of success, both supramolecular and covalent anchoring strategies will be investigated.

Project coordination

Michael Smietana (Institut des Biomolécules Max Mousseron)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

IBMM Institut des Biomolécules Max Mousseron
UPSaclay - BioCIS Université Paris-Saclay - Biomolécules : Conception, Isolement, Synthèse
Queen Mary University of London / Chemistry and Biochemistry
LCC LABORATOIRE DE CHIMIE DE COORDINATION

Help of the ANR 468,439 euros
Beginning and duration of the scientific project: December 2020 - 48 Months

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