Mykhailiuk, Pavel - Enamine Ltd -

个人简介

Education 2017Dr. Sci. in organic chemistry with Prof. A. Tolmachev National Taras Shevchenko University of Kyiv (Ukraine). 2005-08PhD in biochemistry with Prof. A. Ulrich Karlsruhe Institute of Technology (Germany). 2005-08PhD in organic chemistry with Prof. I. Komarov National Taras Shevchenko University of Kyiv (Ukraine). Grants and Awards 2021RSC Fluorine Award for 2021 (under 40). 2020ERC consolidator grant ERC consolidator grant (ID: 101000893). 2018Finalist of “The European Young Chemist Award” (12 European chemists under 35). 2017“Prize of the President of Ukraine for young scientists” (under 40). 2016Finalist of “The European Young Chemist Award” (13 European chemists under 35). 2016“Ukrainian Scopus Award” (under 35). 2015“Prize of National Academy of Science (NAS) of Ukraine” (under 35). 2014Runner-up of EFMC Prize for a Young Medicinal Chemist in Industry (under 35). 2008"Wolff & Sohn-Prize" at Karlsruhe Institute of Technology, (Karlsruhe, Germany). 2000Bronze medal at “32nd International Chemistry Olympiad” (Copenhagen, Denmark). 1999Silver medal at “33d Mendeleev Chemistry Olympiad” (Minsk, Belarus). Research Visits 2018-19Visiting scientist (FulBright scholarship) with Prof. P. Baran (Scripps, USA). 2015-16Visiting scientist (Marie-Curie scholarship) with Prof. J. Cossy (ESPCI, France). 2015Visiting scientist (DAAD scholarship) with Prof. T. Bach (TUM München, Germany),Prof. N. Budisa (TU Berlin, Germany). 2015Invited Professor at University of Cergy-Pontoise by Prof. T. Brigaud (Cergy, France)

研究领域

1. Chemistry of diazo compounds In 2014-17, we developed three novel chemical reagents: difluoromethyl diazomethane (CHF2CHN2), pentafluoroethyl diazomethane (C2F5CHN2), and heptafluoroisopropyl diazomethane (i-C3F7CHN2). We also work with trifluoromethyl diazomethane (CF3CHN2) and cyano diazomethane (CNCHN2). We generate them in situ, and study their reactivity as nucleophiles, electrophiles, in cyclopropanation, carbene insertions, and [3+2]-cycloaddition reactions. 2. 3D-Shaped scaffolds for drug discovery The cores of pyrrolidine and piperidine comprise to the structure of more than 100 FDA-approved drugs. In the loop of the recent concepts scaffold hopping, escape the flatland and conformational restriction, medicinal chemists now tend to use now Fsp3-rich bicyclic building blocks. We therefore develop practical synthetic approaches to novel bicyclic analogues of pyrrolidine/piperidine: spirocycles, fused and bridged amines. We incorporate these structures into drugs, and study the biological properties. For example, the spirocyclic analogue of the local anesthetic Bupivacaine was more active than the original drug. 3. Photochemistry To synthesize bicyclic building blocks for drug discovery, we often use photochemistry. On a gram scale we perform the photochemical syntheses in batch, while on a kg scale – in flow. 4. [3+2]-Cycloadditions We also exploit [3+2]-cycloadditions of azomethine ylides, thicarbonyl ylides, nitriloxides and diazo alkanes to synthesize the pharmacologically relevant five-membered heterocycles: pyrrolidines, tetrahydrothiophenes, isoxazoles, isoxazolines, pyrazoles and pyrazolines. 5. Fluorinated amines Incorporation of fluorine atoms into organic compounds can increase their metabolic stability, and decrease the basicity of the neighboring nitrogen atom. Therefore, we have synthesized a library of novel fluorinated amines for drug discovery: CF3-azetidine, CF3-pyrrolidine and CF3-morpholine. The key step in many syntheses was the transformation of the carboxylic group into the trifluoromethyl one by SF4. 6. Synthesis of analogues of L-Proline We synthesize the novel fluorinated and conformationally restricted analogues of L-Proline. We also study their conformational behavior. For example, derivatives of 2,4-methanoproline stabilize N-trans amide bond: Ktrans/cis > 100. Conformationally restricted prolines are interesting as building blocks for drug discovery, and the fluorinated ones also as 19F-labels to study the peptides. 7. C-H activation of cyclic amino acids New 3D-shaped F(sp3)-rich molecules can be easily accessed by the CH-activation/hydrolysis of the appropriately protected cyclic α-amino acids.

近期论文

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Water-soluble Bioisosteres of the ortho-substituted Phenyl Ring A. Denisenko, P. Garbuz, N. M. Voloshchuk, Y. Holota, P. K. Mykhailiuk* Nat. Chem. 2023, General Synthesis of 3-Azabicyclo[3.1.1]heptanes and Evaluation of Their Properties as Saturated Bioisosteres D. Dibchak, M. Snisarenko, A. Mishuk, O. Shablykin, L. Bortnichuk, O. Klymenko-Ulianov, Y. Kheylik, I. V. Sadkova, H. S. Rzepa, P. K. Mykhailiuk* Angew. Chem. Int. Ed. 2023, e202304246 Catalytic undirected borylation of tertiary C–H bonds in bicyclo[1.1.1]pentanes and bicyclo[2.1.1]hexanes I. F. Yu, J. L. Manske, A. Diéguez-Vázquez, A. Misale, A. E. Pashenko, P. K. Mykhailiuk, S. V. Ryabukhin, D. M. Volochnyuk, J. F. Hartwig Nat. Chem. 2023, 15, 685-693 C−H Activation of Unbiased C(sp3)−H Bonds: Gold(I)-Catalyzed Cycloisomerization of 1-Bromoalkynes R. Miguélez, N. Semleit, C. Rodríguez-Arias, P. Mykhailiuk, J. M. González, G. Haberhauer, P. Barrio* Angew. Chem. Int. Ed. 2023, e202305296 Rapid and scalable halosulfonylation of strain-release reagents H. D. Pickford, V. Ripenko, R. E. McNamee, S. Holovchuk, A. L. Thompson, R. C. Smith, P. K. Mykhailiuk,* E. A. Anderson* Angew. Chem. Int. Ed. 2023, 62, e202213508 General and Scalable Approach to Trifluoromethyl-Substituted Cyclopropanes V. Ahunovych, A. A. Klipkov, M. Bugera, K. Tarasenko, S. Trofymchuk, O. Stanko, A. Boretskyi, M. Zheludenko, I. V. Sadkova, P. K. Mykhailiuk* J. Org. Chem. 2023, 88, 3859-3870 Fluorinated Aliphatic Diazirines: Preparation, Characterization, and Photolabeling Studies U. Kornii, O. Shablykin, T. Tarasiuk, O. Stepaniuk, V. Matvienko, D. Aloshyn, N. Zahorodniuk, P. K. Mykhailiuk* J. Org. Chem. 2023, 88, 1-17 Arylboration of Enecarbamates for the Synthesis of Borylated Saturated N-Heterocycles G. L. Trammel, P. B. Kannangara, D. Vasko, O. Datsenko, P. Mykhailiuk, M. K. Brown* Angew. Chem. Int. Ed. 2022, 61, e202212117 A Practical and Scalable Approach to Fluoro-Substituted Bicyclo[1.1.1]pentanes R. Bychek, P. K. Mykhailiuk* Angew. Chem. Int. Ed. 2022, 61, e202205103 Overcoming Limitations in Decarboxylative Arylation via Ag–Ni Electrocatalysis M. D. Palkowitz, G. Laudadio, S. Kolb, J. Choi, M. S. Oderinde, T. El-Hayek Ewing, P. N. Bolduc, T. Chen, H. Zhang, P. T. W. Cheng, B. Zhang, M. D. Mandler, V. D. Blasczak, J. M. Richter, M. R. Collins, R. L. Schioldager, M. Bravo, T. G. M. Dhar, B. Vokits, Y. Zhu, P.-G. Echeverria, M. A. Poss, S. A. Shaw, S. Clementson, N. N. Petersen, P. K. Mykhailiuk, P. S. Baran* J. Am. Chem. Soc. 2022, 121, 17709-17720 Unexpected Isomerization of Oxetane-Carboxylic Acids B. Chalyk, A. Grynyova, K. Filimonova, T. V. Rudenko, D. Dibchak, P. K. Mykhailiuk* Org. Lett. 2022, 24, 4722-4728 Fluorine-Containing Prolines: Synthetic Strategies, Applications, and Opportunities P. K. Mykhailiuk* J. Org. Chem. 2022, 87, 6961-7055 When SF5 outplays CF3: Effects of pentafluorosulfanyl decorated scorpionates on copper A. Noonikara Poyil, A. Muñoz-castro, A. Boretskyi, P. K. Mykhailiuk,* R. Dias* Chem. Sci. 2021, 12, 14618-14623 Oxa-spirocycles: synthesis, properties and applications K. Fominova, T. Diachuk, D. Granat, T. Savchuk, V. Vilchynskyi, O. Svitlychnyi, V. Meliantsev, I. Kovalchuk, E. Litskan, V. V. Levterov, V. R. Badlo, R. I. Vaskevych, A. I. Vaskevych, A. V. Bolbut, V. V. Semeno, R. Iminov, K. Shvydenko, A. S. Kuznetsova, Y. V. Dmytriv, D. Vysochyn, V. Ripenko, A. A. Tolmachev, O. Pavlova, H. Kuznietsova, I. Pishel, P. Borysko, P. K. Mykhailiuk* Chem. Sci. 2021, 12, 11294-11305 Fluorinated Pyrazoles: From Synthesis to Applications P. K. Mykhailiuk* Chem. Rev. 2021, 121, 1670-1715 Large-Scale Synthesis and Modifications of Bicyclo[1.1.1]pentane-1,3-dicarboxylic Acid (BCP) V. Ripenko, D. Vysochyn, I. Klymov, S. Zhersh, P. K. Mykhailiuk* J. Org. Chem. 2021, 86, 14061-14068 Bicyclic Pyrrolidines for Medicinal Chemistry via [3 + 2]-Cycloaddition V. I. Savych, V. L. Mykhalchuk, P. V. Melnychuk, A. O. Isakov, T. Savchuk, V. M. Timoshenko, S. A. Siry, S. O. Pavlenko, D. V. Kovalenko, O. V. Hryshchuk, V. A. Reznik, B. A. Chalyk, V. S. Yarmolchuk, E. B. Rusanov, P. K. Mykhailiuk* J. Org. Chem. 2021, 86, 13289-13309 Phosphine Oxides (−POMe2) for Medicinal Chemistry: Synthesis, Properties, and Applications M. V. Stambirskyi, T. Kostiuk, S. I. Sirobaba, A. Rudnichenko, D. L. Titikaiev, Y. V. Dmytriv, H. Kuznietsova, I. Pishel, P. Borysko, P. K. Mykhailiuk* J. Org. Chem. 2021, 86, 12783-12801 Scalable Approach to Fluorinated Heterocycles with Sulfur Tetrafluoride (SF4) S. Trofymchuk, M. Bugera, A. A. Klipkov, V. Ahunovych, B. Razhyk, S. Semenov, A. Boretskyi, K. Tarasenko, P. K. Mykhailiuk* J. Org. Chem. 2021, 86, 12181-12198 Bicyclic Piperidines via [2 + 2] Photocycloaddition V. Shcherbakova, D. Dibchak, M.Snisarenko, Y. Skalenko, A. V. Denisenko, A. S. Kuznetsova, P. K. Mykhailiuk* J. Org. Chem. 2021, 86, 2200-2209 2,2,2-Trifluorodiazoethane (CF3CHN2): A Long Journey since 1943 P. K. Mykhailiuk* Chem. Rev. 2020, 120, 22, 12718-12755 Saturated Bioisosteres of ortho‐Substituted Benzenes A. Denisenko, P. Garbuz, S. V. Shishkina, N. M. Voloshchuk, P. K. Mykhailiuk* Angew. Chem. Int. Ed. 2020, 59, 46, 20515-20521 Water‐soluble non‐classical benzene mimics V. Levterov, Y. Panasyuk, V. Pivnytska, P. K. Mykhailiuk* Angew. Chem. Int. Ed. 2020, 59, 18, 7161-7167 Deoxofluorination of (Hetero)aromatic Acids S. Trofymchuk, M. Ya. Bugera, A. A. Klipkov, B. Razhyk, S. Semenov, K. Tarasenko, V. S. Starova, O. A. Zaporozhets, O. Yu. Tananaiko, A. N. Alekseenko, Y. Pustovit, O. Kiriakov, I. I. Gerus, A. A. Tolmachev, P. K. Mykhailiuk* J. Org. Chem. 2020, 85, 5, 3110-3124 Diazoacetonitrile (N2CHCN): a long forgotten but valuable reagent for organic synthesis P. K. Mykhailiuk,* R. M. Koenigs* Сhem. Eur. J. 2020, 26, 1, 89-101 Convenient Access to Conformationally Rigid Sultams D. Dibchak, V. Scherbacova, A. V. Denisenko, P. K. Mykhailiuk* Org. Lett. 2019, 21, 22, 8909-8914 Difluoro-Substituted bicyclo[1.1.1]pentanes as Novel Motifs for Medicinal Chemistry: Design, Synthesis and Characterization R. M. Bychek, V. Hutskalova, J. P. Bas, O. A. Zaporozhets, S. Zozulia, V. V. Levterov, P. K. Mykhailiuk* J. Org. Chem. 2019, 84, 23, 15106-15117 Deoxofluorination of Aliphatic Carboxylic Acids: A Route to Trifluoromethyl-Substituted Derivatives M. Bugera. S. Trofymchuk, K. Tarasenko, O. Zaporozhets, Y. Pustovit, P. K. Mykhailiuk* J. Org. Chem. 2019, 84, 26, 16105-16115 Hindered dialkyl ether synthesis via electrogenerated carbocations J. Xiang, M. Shang, Y. Kawamata, H. Lundberg, S. Reisberg, M. Chen, P. Mykhailiuk, G. Beutner, M. Collins, A. Davies, M. Del Bel, G. Gallego, J. Spangler, J. T. Starr, S. Yang, D. Blackmond, P. Baran Nature 2019, 573, 398-402 A radical approach to anionic chemistry: synthesis of ketones, alcohols, and amines S. Ni, N. M. Padial, C. Kingston, J. C. Vantourout, D. C. Schmitt, J. T. Edwards, M. M. Kruszyk, R. R. Merchant, P. K. Mykhailiuk, B. B. Sanchez, S. Yang, M. A. Perry, G. M. Gallego, J. J. Mousseau, M. R. Collins, R. J. Cherney, P. S. Lebed, J. S. Chen, T. Qin, P. S. Baran J. Am. Chem. Soc. 2019, 141, 6726-6739 Electrochemical C(sp3)–H Fluorination Y. Takahira, M. Chen, Y. Kawamata, P. Mykhailiuk, H. Nakamura, B. K. Peters, S. H. Reisberg, C. Li, L. Chen, T. Hoshikawa, T. Shibuguchi, P. S. Baran Carbonyl complexes of copper(I) stabilized bybridging fluorinated pyrazolates and halide ions D. Parasar, N. B. Jayaratna, A. Muñoz-Castro, A. E. Conway, P. K. Mykhailiuk, H. V. R. Dias Quaternary Centers via Ni-Catalyzed Cross-Coupling of Tertiary Carboxylic Acids and Aryl Zinc Reagents T. -G. Chen, H. Zhang, P. K. Mykhailiuk, R. R. Merchant, C. A. Smith, T. Qin, P. S. Baran Angew. Chem. Int. Ed. 2019, 59, 2454-2458 CH-Activation of Proline analogues V. Hutskalova, P. K. Mykhailiuk* Org. Biomol. Chem. 2019, 17, 4342-4349 Saturated Bioisosteres of Benzene: Where to go Next? P. K. Mykhailiuk* Org. Biomol. Chem. 2019, 17, 2839-2849 Difluorodiazoethane (CF2HCHN2): a new reagent for the introduction of the difluoromethyl group P. K. Mykhailiuk,* R. M. Koenigs* Chem. Eur. J. 2019, 25, 6053-6063 Practical synthesis of 2,2-disubstituted spirocyclic pyrrolidines by Dieckmann condensation K. Fominova, T. Diachuk, I. Sadkova, P. K. Mykhailiuk* Eur. J. Org. Chem. 2019, 22, 3553-3559