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Bastien Nay
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Radulanine A: discovery of a natural herbicide

Bastien Nay, CNRS Research Director at the Organic Synthesis Laboratory (LSO*)

The use of syn­thet­ic pes­ti­cides and her­bi­cides is a sen­si­tive sub­ject in terms of pub­lic opin­ion, who are often con­cerned about the safe­ty of exposed pop­u­la­tions and bio­di­ver­si­ty. With­out enter­ing too much into this debate, it must nev­er­the­less be stressed that the search for sus­tain­able solu­tions and alter­na­tives is an active field in chem­istry, par­tic­u­lar­ly focused on nat­ur­al substances.

In organ­ic chem­istry, we some­times play Lego with atoms to repro­duce small nat­ur­al mol­e­cules with inter­est­ing prop­er­ties. This is what we call total syn­the­sis. Once these mol­e­cules have been syn­the­sised, we try to bring them to life through new applications.

Research in this field has already made it pos­si­ble to bring mol­e­cules of nat­ur­al ori­gin onto the mar­ket. To give an idea of the extent of the phe­nom­e­non, it should be not­ed that about a third of the pes­ti­cides patent­ed between 1997 and 2010 are “nat­ur­al” 1. Alter­na­tives there­fore exist, but “nat­ur­al” does not nec­es­sar­i­ly mean “safe”.

This fig­ure is much low­er in the cat­e­go­ry of her­bi­cides: over the same peri­od, only 8% of patent­ed mol­e­cules are “nat­ur­al”. It is in this con­text that we dis­cov­ered a nat­ur­al her­bi­cide with poten­tial appli­ca­tions. Notably in agri­cul­ture, but also in the treat­ment of rail­way tracks, which must remain per­fect­ly free from weeds to run high-speed trains on them, for exam­ple. Our project is financed by the inno­va­tion clus­ters at the CNRS 2 and Insti­tut Poly­tech­nique de Paris 3.

Bastien Nay

Unex­pect­ed discovery

In May 2019 our team from the Organ­ic Syn­the­sis Lab­o­ra­to­ry of École poly­tech­nique 4 announced that we had suc­ceed­ed in syn­the­sis­ing a nat­ur­al her­bi­cide: Radu­lanin A. The sto­ry is an exam­ple of “serendip­i­ty” – the abil­i­ty to make a sci­en­tif­ic dis­cov­ery by chance and grasp its use­ful­ness. For it was not a new her­bi­cide that we were work­ing on at first, but rather a new method of syn­the­sis, tar­get­ing com­plex molecules.

The mol­e­cules tar­get­ed in our research are often com­plex and require long-term work. Basi­cal­ly, what we were aim­ing for was a mol­e­cule pro­duced by a fun­gus; a com­plex mol­e­cule with cer­tain motifs that inter­est­ed us. To repro­duce these motifs (sev­en-chain oxy­genat­ed cycles) we devel­oped a new method of syn­the­sis, using a par­tic­u­lar chem­i­cal reac­tion (for the spe­cial­ists read­ing, this was by a rearrange­ment of the retro-Claisen type). To test the use­ful­ness of this method, we there­fore chose a sim­pler mol­e­cule: Radu­lanin A. And, low and behold, our method of syn­the­sis worked. In the begin­ning, there­fore, Radu­lanin A was not specif­cal­ly our target.

First reflex: find an application

Once syn­the­sised, the ques­tion arose as to how this mol­e­cule is used in nature. In doing so, we dis­cov­ered that it has sim­i­lar­i­ties with mol­e­cules known to have plant hor­mone prop­er­ties. A fel­low researcher from Sor­bonne Uni­ver­si­ty, Emmanuel Bau­douin, then took over and showed that Radu­lanin A does indeed have the abil­i­ty to inter­act with plants, through phy­to­tox­ic prop­er­ties. With­out know­ing it, we had syn­the­sised a nat­ur­al herbicide!

At a time when we are look­ing for indus­tri­al alter­na­tives to glyphosate, this was good news. The her­bi­ci­dal prop­er­ty of Radu­lanin A has now been patent­ed, and indus­try is inter­est­ed in it. For the patent to be exploit­ed, it will be nec­es­sary to under­stand how, over time, the mol­e­cule inter­acts with the envi­ron­ment, and whether it can have effects on the human body. These ques­tions, cen­tral to indus­try, are a pre­req­ui­site for approval. The impact of a mol­e­cule also depends on how it is used, which must remain rea­son­able to lim­it its impact on the envi­ron­ment. The tox­i­c­i­ty of a sub­stance is almost always a mat­ter of concentration.

1B. Nay, W. Zhang. Nature chim­ique her­bi­cide : Le poten­tiel des sub­stances naturelles en agri­cul­ture. Revue des Oeno­logues, juil­let 2019, 172, 9–11
2https://​nay​group​.word​press​.com/​2​0​2​0​/​0​2​/​0​8​/​o​n​-​t​h​e​-​s​t​a​r​t​i​n​g​-​b​l​o​c​k​s​-​w​i​t​h​-​c​n​r​s​-​i​n​n​o​v​a​t​i​o​n​-​f​o​r​-​t​h​e​-​d​e​v​e​l​o​p​m​e​n​t​-​o​f​-​h​e​r​b​i​c​i​d​e​-​n​a​t​u​r​a​l​-​p​r​o​d​ucts/
3https://​nay​group​.word​press​.com/​2​0​2​1​/​0​2​/​2​7​/​i​p​-​p​a​r​i​s​-​f​u​n​d​s​-​o​u​r​-​p​r​e​m​a​t​u​r​a​t​i​o​n​-​p​r​o​j​e​c​t​-​o​n​-​t​h​e​-​d​e​v​e​l​o​p​m​e​n​t​-​o​f​-​n​a​t​u​r​a​l​-​w​e​e​d​k​i​l​lers/
4http://​lso​.poly​tech​nique​.fr/

Contributors

Bastien Nay
Bastien Nay
CNRS Research Director at the Organic Synthesis Laboratory (LSO*)

After 13 years at the Muséum National d'Histoire Naturelle, Bastien Nay joined the Organic Synthesis Laboratory (*LSO: a joint research unit of CNRS, École Polytechnique - Institut Polytechnique de Paris and ENSTA Paris) in 2017 to develop his research in organic chemistry, aiming to achieve the synthesis of natural substances of interest and not easily accessible by other means. In particular, he is interested in methods for the rapid generation of molecular complexity and diversity.