Radulanine A : discovery of a natural herbicide

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.

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.

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.