Development of novel fluorinated reagents for preparation of drugs.

Project Information

FLUNOVELTY

Grant agreement ID: 654260

DOI

10.3030/654260

Project closed

EC signature date 26 March 2015

Start date 1 November 2015

End date 31 October 2016

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 92 538,00

EU contribution

€ 92 538,00

Coordinated by

ECOLE SUPERIEURE DE PHYSIQUE ET DECHIMIE INDUSTRIELLES DE LA VILLE DEPARIS
France

Periodic Reporting for period 1 - FLUNOVELTY (Development of novel fluorinated reagents for preparation of drugs.)

Reporting period: 2015-11-01 to 2016-10-31

Summary of the context and overall objectives of the project

The main objectives of Flunovelty project, performed at ESPCI (Paris, France) by Pavel Mykhailiuk with Prof. Janine Cossy, were to (a) develop the novel small fluorinated reagents; (b) to elaborate their novel reactions; and to (c) use this knowledge to discover novel synthetic approaches towards some known drugs.

In fact, during this project we discovered the novel chemical reagent: difluoromethyldiazomethane (CF2HCHN2), and elaborated its chemistry. In particular, we used this reagent to synthesize diversely substituted difluoromethylpyrazoles: the core structures of known argochemicals: Bixafen (Bayer), Sedaxane (Syngenta), Fluxapyroxad (BASF) and Isopyrazam (Syngenta).

In summaty, we have discovered a novel and cheaper approach to known agrochemicals. We believe that these methods will be finally implemented by agrochemical companies that will result in lowering the price of the corresponding pesticides, and eventually the food.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

"
Report time: 01.11.2015-01.02.2016 (3 months)
During this time we have discovered the novel reactivity mode for CF3CHN2. We have performed the corresponding synthetic experiments and already written the manuscript (attached). In this work we have also synthesized an analogues of the known antibiotic - Ciprofloxacin. The manuscript has been already published in one of the the most prestigious chemistry journals - Organic Letters.
(1) ""Unexpected Reactivity of Trifluoromethyl Diazomethane (CF3CHN2): Electrophilicity of the Terminal N-Atom.""
Arkhipov A. V.; Arkhipov V. V.; Cossy J.; Kovtunenko V. O.; Mykhailiuk P. K.
Org. Lett. 2016, 18 (14), 3406-3409.
Financial support by Marie-Curie (Horizon 2020, 654260) is acknowledged in the manuscript.

Report time: 01.02.2015-31.10.2016 (9 months)
During this time we have accomplished several projects on the novel reactivity of CF3CHN2, C2F5CHN2 and CF2HCHN2. We have performed the corresponding synthetic experiments and already written two manuscripts. One manuscript has already been published, while another one is accepted:
(2) ""Synthesis of Fluoroalkyl Pyrazoles from In-Situ-Generated C2F5CHN2 and Electron-Deficient Alkenes.""
Mykhailiuk P.; Ishchenko A.; Stepanenko V.; Cossy J.
Eur. J. Org. Chem. 2016, in press (DOI: 10.1002/ejoc.201600947).
(3) ""Synthesis of CF2H-pyrazolines by [3+2]-cycloaddition between CF2HCHN2 and electron-deficient alkenes.""
Jue Li, Xin-Ling Yu, Janine Cossy, Song-Yang Lv, Hai-Long Zhang, Fu Su, Li Hai, Pavel K. Mykhailiuk, Yong Wu
Eur. J. Org. Chem. 2016, accepted (DOI: 10.1002/ejoc.201610165).
The text of the both manuscripts is attached.
Financial support by Marie-Curie (Horizon 2020, 654260) is acknowledged in the both manuscripts.
"

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

In this part of the project we have already synthesized an analogue of the known antibacterial drug - Ciprofloxacin. We have tested its activity, and it is more potent over the known drug. Given the ongoing need of modern society on novel antibioticks (antibacterial resistence), we do belive that this finding might bright a huge impact to the pharmaceutical industry.

Also, we have discovered a novel achemical reagent - difluoromethyldiazomethane, - and used it to synthesize diverse difluoromethylated pyrazoles - the core of known argochemicals: Bixafen (Bayer), Sedaxane (Syngenta), Fluxapyroxad (BASF) and Isopyrazam (Syngenta). Hence, we we believe that this method will be finally implemented by agrochemical companies that will result in lowering the price of the corresponding pesticides, and finally the food.

Graphical abstract for the manuscript to be submitted