Research

The cernak lab studies the interface of chemical synthesis and computer science. A small molecule’s structure encodes its function, so synthetic strategies that access diverse molecular structures are paramount to the invention of novel functional molecules such as dyes, fragrances or pharmaceuticals. We use algorithms, robotics and data science to study new chemical reactions, synthetic routes to natural products, and biochemical probes. Our lab employs informatics in reaction discovery, total synthesis, cell imaging and medicinal chemistry. Researchers in the group learn high-throughput experimentation, basic coding, and modern synthetic techniques. By studying the relationship of chemical synthesis to functional properties, we pursue the opportunity to positively impact human health.

Members

Yingfu Lin

Postdoctoral Fellow

Zirong Zhang

Postdoctoral Fellow

James Douthwaite

Postdoctoral Fellow

Yuning Shen

Graduate Student

Sam Zhang

Graduate Student

Di Wang

Graduate Student

Andrew Outlaw

Graduate Student

Jordan Bench

Undergraduate Student

Christopher Audu

Postdoctoral Fellow

Andrew McGrath

Graduate Student

Babak Mahjour

Graduate Student

Eunjae Shim

Graduate Student

Ruheng Zhao

Graduate Student

Publications

Zirong Zhang and Tim Cernak. The Formal Cross-Coupling of Amines and Carboxylic Acids to Form sp3–sp3 Carbon–Carbon Bonds. Angew. Chem. Int. Ed. 2021, 10.1002/anie.202112454 [link]

Babak Mahjour and Tim Cernak. Phactor™ – a High Throughput Experimentation Management System. [preprint]

Babak Mahjour, Yuning Shen, Tim Cernak. Ultrahigh-Throughput Experimentation for Information-Rich Chemical Synthesis. Acc. Chem. Res. 2021, 54, 2337–2346. [link]

Yuning Shen, Julia E. Borowski, Melissa A. Hardy, Richmond Sarpong, Abigail G. Doyle, Tim Cernak. Automation and computer-assisted planning for chemical synthesis. Nat. Rev. Methods Primers, 2021, 1, 23. [link]

Yingfu Lin, Zirong Zhang, Babak Mahjour, Di Wang, Rui Zhang, Eunjae Shim, Andrew McGrath, Yuning Shen, Nadia Brugger, Rachel Turnbull, Shashi Jasty, Sarah Trice, Tim Cernak. Reinforcing the Supply Chain of COVID-19 Therapeutics with Expert-Coded Retrosynthetic Software. [preprint]

Babak Mahjour, Yuning Shen, Wenbo Liu, and Tim Cernak. A map of the amine-carboxylic acid coupling system, Nature, 2020, 580, 71–75. [link]

Mycah R. Uehling, Ryan P. King, Shane W. Krska, Tim Cernak and Stephen L. Buchwald. Pharmaceutical Diversification via Palladium Oxidative Addition Complexes, Science, 2019, 363, 405–408. [link]

Hazel Wong and Tim Cernak. Reaction Miniaturization in Eco-Friendly Solvents, Current Opinion Green & Sustainable Chemistry, 2018, 11, 91–98. [link]

Shishi Lin, Sergei Dikler, Ronald D. Ferguson, Robert P. Sheridan, Zhengwei Peng, Donald V. Conway, Kerstin Zawatzky, Heather Wang, Tim Cernak, Ian W. Davies, Daniel A. DiRocco, Huaming Sheng, Christopher J. Welch, Spencer D. Dreher, Mapping the Dark Space of Chemical Reactions with Extended Nanomole Synthesis and MALDI-TOF MS, Science, 2018, 361, 1–7. [link]

Nathan J. Gesmundo, Bérengère Sauvagnat, Patrick Curran, Matthew P. Richards, Christine L. Andrews, Peter J. Dandliker, Tim Cernak. Nanoscale Synthesis and Affinity Ranking, Nature, 2018, 557, 228–232. [link]

Tim Cernak. A Machine with Chemical Intuition, Chem. 2018, 4, 401–403. [link]

Tim Cernak, Nathan Gesmundo, Kevin D. Dykstra, Yang, Yu, Zhicai Wu, Zhi-Cai Shi, Petr Vachal, Donald Sperbeck, Shuwen He, Beth Murphy, Lisa Sonatore, Steven Williams, Maria Madeira, Andreas Verras, Maud Reiter, Claire Lee, James Cuff, Edward Sherer, Jeffrey Kuethe, Stephen Goble, Nicholas Perrotto, Shirly Pinto, Dong-Ming Shen, Ravi Nargund, James Balkovec, Robert DeVita, Spencer Dreher. Microscale High-Throughput Experimentation as an Enabling Technology in Drug Discovery: Application in the Discovery of (Piperidinyl)pyridinyl-1H-benzimidazole Diacylglycerol Acyltransferase 1 Inhibitors, J. Med. Chem. 2017, 60, 3594–3605. Featured Article. [link]

Tim Cernak. Synthesis in the Chemical Space Age, Chem. 2016, 1, 6–9. [link]

Peter S. Kutchukian, James F. Dropinski, Kevin D. Dykstra, Bing Li, Daniel A. DiRocco, Eric C. Streckfuss, Louis-Charles Campeau, Tim Cernak, Petr Vachal, Ian W. Davies, Shane W. Krska and Spencer D. Dreher. Chemistry Informer Libraries: A Chemoinformatics Enabled Approach to Evaluate and Advance Synthetic Methods, Chem. Sci. 2016, 7, 2604–2613. [link]

Tim Cernak, Kevin D. Dykstra, Sriram Tyagarajan, Petr Vachal and Shane W. Krska. The Medicinal Chemist’s Toolbox for Late Stage Functionalization of Drug-Like Molecules, Chem. Soc. Rev. 2016, 45, 546–576. [link]

Alexander Buitrago Santanilla, Erik L. Regalado, Tony Pereira, Kevin Bateman, Louis-Charles Campeau, Simon Berritt, Yong Liu, Michael Shevlin, Zhi-Cai Shi, Jonathan Schneeweis, Christopher J. Welch, Roy Helmy, Petr Vachal, Ian Davies, Tim Cernak and Spencer Dreher. Nanomolar-Scale High-Throughput Chemistry for the Synthesis of Complex Molecules, Science, 2015, 347, 49–53. [link]

Shuwen He, Qingmei Hong, Zhong Lai, David X. Yang, Pauline C. Ting, Jeffrey T. Kuethe, Timothy A. Cernak, Kevin D. Dykstra, Donald M. Sperbeck, Zhicai Wu, Yang Yu, Ginger X. Yang, Tianying Jian, Jian Liu, Deodial Guiadeen, Arto D. Krikorian, Lisa M. Sonatore, Judyann Wiltsie, Jinqi Liu, Judith N. Gorski, Christine C. Chung, Jack T. Gibson, JeanMarie Lisnock, Jianying Xiao, Michael Wolff, Sharon X. Tong, Maria Madeira, Bindhu V. Karanam, Dong-Ming Shen, James M. Balkovec, Shirly Pinto, Ravi P. Nargund, and Robert J. DeVita. Discovery of a Potent and Selective DGAT1 Inhibitor with a Piperidinyl-oxy-cyclohexanecarboxylic Acid Moiety, ACS Med. Chem. Lett. 2014, 5, 1082–1087. [link]

Heike Schönherr and Tim Cernak. Profound Methyl Effects in Drug Discovery and a Call for New C-H Methylation Reactions, Angew. Chem. Int. Ed. 2013, 52, 12256–12267. [link]

Timothy Cernak, Kevin Dykstra, Dorothy Levorse, Andreas Verras, James Balkovec, Ravi Nargund and Robert DeVita. Synthesis of Oxaspiropiperidines as a Strategy for Lowering logD, Tetrahedron Lett. 2011, 52, 6457–6459. [link]

Lisa A. Ambrosini, Tim A. Cernak and Tristan H. Lambert. “Total Synthesis of the Tylophora Alkaloids Rusplinone, 13aα-Secoantofine, and Antofine using a Multicatalytic Oxidative Aminochlorocarbonylation / Friedel-Crafts Reaction”, Tetrahedron, 2010, 66(26), 4882–4887.

Lisa A. Ambrosini, Tim A. Cernak and Tristan H. Lambert. “Development of Oxidative Formylation and Ketonylation Reactions”, Synthesis, 2010, 41(28), 870–881.

Tim A. Cernak and Tristan H. Lambert. “Multicatalytic Synthesis of α-Pyrrolidinyl Ketones via a Tandem Palladium(II)/Indium(III)-Catalyzed Aminochlorocarbonylation/Friedel-Crafts Acylation Reaction”, The Journal of the American Chemical Society, 2009, 131(9), 3124–3125.

Jonathan Hudon, Timothy A. Cernak, James A. Ashenhurst and James L. Gleason. “Stable 5-Substituted Cyclopentadienes for the Diels-Alder Cycloaddition and Their Application to Palau’amine Synthesis”, Angewandte Chemie International Edition in English, 2008, 47, 8885–8888.

Timothy A. Cernak and James L. Gleason. “DFT Guided Design of Exo-Selective Dehydroalanine Dienophiles for Application Towards Palau’amine”, Journal of Organic Chemistry, 2008, 73(1), 102–110.

Timothy A. Cernak and James L. Gleason. “Synthesis of 5-Chloromethylene Hydantoins and Thiohydantoins”, Heterocycles, 2007, 71(1), 117–134.

Nigel J. Eggers, John D. Greenough, Tim Cernak. “Classification of British Columbia’s Okanagan Chardonnay Wines by Origin Using Volatile Components”, in “Fine Wine and Terroir: A Geoscience Perspective” ed. R. W. MacQueen, L. D. Meinert. Canada: St. John’s: Geological Association of Canada. 2006, pp. 183–19

Patents

Kun Liu, Abdelghani Achab, Purakkattle Biju, Timothy A. Cernak, Yongqi Deng, Xavier Fradera, Liangqin Guo, Yongxin Han, Shuwen He, Joseph Kozlowski, Derun Li, Guoqing Li, Qinglin Pu, Zhi-Cai Shi, Wensheng Yu, Hongjun Zhang. “Novel substituted N'-hydroxycarbamimidoyl-1,2,5-oxadiazole compounds as indoleamine 2,3-dioxygenase (IDO) inhibitors”, PCT International Application, 2018, WO2018044663A1.

Dong-Ming Shen, Melissa Egbertson, Richard Berger, Xiaoxia Qian, Yimin Qian, Bart Harper, Meng Yang, Zack Zhi Qiang Guo, Vanessa L. Rada, Deping Wang, Timothy A. Cernak, Christopher J. Sinz, Ming Wang, Jonathan E. Wilson, Shimin Xu. “Pyrimidonecarboxamide compounds as PDE2 inhibitors and their preparation”, PCT International Application, 2015, WO2015096651.

Xiaoqing Han, Alan Whitehead, Subharekha Raghavan, Timothy A. Cernak, Spencer Dreher, Jonathan Groeper, Lian Guo, Yong Zhang. ”Pyrrolopyrimidinone derivatives as soluble guanylate cyclase activators and their preparation”, PCT International Application, 2015, WO2015088886.

Timothy A. Cernak, Kevin D. Dykstra, Dong-Ming Shen, Kun Liu, Andrew Stamford, John Qiang Tan. “Preparation of indazole derivatives as mineralocorticoid receptor antagonists for the treatment of aldosterone-mediated diseases”, PCT International Application, 2014, WO2014014794.

Robert J. DeVita, Shuwen He, Jian Liu, Timothy A. Cernak, Arto D. Krikorian, Ginger Xuqiang Yang, Zhicai Wu; Yang Yu, Dong-Ming Shen, Zhong Lai, Qingmei Hong, Ravi P. Nargund. “Preparation of triazolylpyridine derivatives and analogs for use as DGAT-1 inhibitors”, PCT International Application, 2013, WO201306093.

Timothy A. Cernak, Robert J. DeVita, Yang Yu, Zhicai Wu, Kevin D. Dykstra, Andreas Verras, James M. Balkovec, Alan Whitehead. “Preparation of bicyclo[2.2.2]octane-1-carboxylic acid derivatives as DGAT1 inhibitors for treatment of diabetes and obesity”, PCT International Application, 2013, WO2013068328.

Jian Liu, James M. Balkovec, Arto D. Krikorian, Deodial Guiadeen, Ginger Yang, Tianying Jian, Zhicai Wu, Yang Yu, Ravi P. Nargund, Petr Vachal, Robert J. DeVita, Shuwen He, Zhong Lai, Radhika M. Blevis-Bal, Timothy A. Cernak, Donald M. Sperbeck, Qingmei Hong. "Preparation of imidazopyridinzylphenylpyridinylpiperidinylacetic acid derivatives and analogs for use as DGAT1 inhibitors", PCT International Application, 2012, WO2012096813.

Timothy A. Cernak, James M. Balkovec, Ravi P. Nargund, Maud Reiter, Donald M. Sperbeck, Kevin D. Dykstra, Yang Yu, Spencer Dreher, Kevin M. Maloney, Zhicai Wu, Robert J. DeVita, Andreas Verras. "Spirocyclic Compounds for Treatment of Obesity and Diabetes", PCT International Application, 2012, WO2012009217.

 Book Chapters

Outlaw, A., Cernak, T., Li, J. J. Odevixibat (Bylvay): A Selective Inhibitor of the Ileal Bile Acid Transporter. In Chem. and Pharm. of Drug Discov. John Wiley & Sons, 2024, 381–401. ISBN: 978-1-394-22512-5

 Contact

tcernak@umich.edu

+1.734.615.2178

3815 CHEM
Chemistry
930 North University Avenue
Ann Arbor, Michigan 48109 USA

 Apply

Grow with us! We are looking for graduate students and postdoctoral fellows with an interest in chemical synthesis and data science.

Future graduate students should apply here.

Future postdoctoral fellows should contact Timothy Cernak.

 Images of TTP mosquito ® liquid handling robot from TTP Labtech