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Access to Unnatural α-Amino Acids via Visible-Light-Mediated Decarboxylative Conjugate Addition to Dehydroalanine

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Download Hi-Res ImageDownload to MS-PowerPointCite This:Org. Lett. 2020, 22, 6, 2196-2200
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    Access to Unnatural α-Amino Acids via Visible-Light-Mediated Decarboxylative Conjugate Addition to Dehydroalanine
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    • Akshay A. Shah*
      Akshay A. Shah
      Department of Discovery Chemistry, Merck & Company, Inc., 770 Sumneytown Pike, West Point, Pennsylvania 19486, United States
      *Email: [email protected]
      More by Akshay A. Shah
      Orcidhttp://orcid.org/0000-0001-9451-0869
    • Michael J. Kelly III
      Michael J. Kelly, III
      Department of Discovery Chemistry, Merck & Company, Inc., 770 Sumneytown Pike, West Point, Pennsylvania 19486, United States
      More by Michael J. Kelly, III
    • James J. Perkins
      James J. Perkins
      Department of Discovery Chemistry, Merck & Company, Inc., 770 Sumneytown Pike, West Point, Pennsylvania 19486, United States
      More by James J. Perkins
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    Organic Letters

    Cite this: Org. Lett. 2020, 22, 6, 2196–2200
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    https://doi.org/10.1021/acs.orglett.0c00371
    Published February 28, 2020
    Copyright © 2020 American Chemical Society
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    Abstract

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    An expedient synthesis of β-alkyl α-amino acids is reported via application of decarboxylative photocatalysis. The method utilizes abundant, diverse, and inexpensive carboxylic acids to provide radicals for conjugate addition to dehydroalanine ester. High-throughput experimentation revealed an acridinium-based photocatalyst, tetraMeO-Acri-N-diMeOPh, to be the optimal choice enabling a general method that is tolerant to a wide range of functional groups. A scalable batch protocol and a parallel library synthesis for accessing diverse unnatural α-amino acids are described.

    Copyright © 2020 American Chemical Society

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    Cited By

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    This article is cited by 43 publications.

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    2. Jonathan N. Gruhin, Richard Kim, Aristidis Vasilopoulos, Eric A. Voight, Erik J. Alexanian. Homologation of Carboxylic Acids Using a Radical-Polar Conjunctive Reagent. Journal of the American Chemical Society 2024, 146 (48) , 32919-32924. https://doi.org/10.1021/jacs.4c13687
    3. Subhodeep Das, Sk Abdur Rahaman, Kangkan Pradhan, Ranjan Jana. Organophotoredox-Catalyzed Synthesis of Unnatural α/β Amino Acids and Peptides via Deaminative Three-Component Coupling. Organic Letters 2024, 26 (33) , 6955-6960. https://doi.org/10.1021/acs.orglett.4c02152
    4. Yue Dong, Xiang Meng, Giri Gnawali, Mengyang Chang, Wei Wang. Photoredox Catalytic Installation of an Alkyl/Aryl Side Chain and Deuterium into (S)-Methyleneoxazolidinone: Synthesis of Enantioenriched α-Deuterated α-Amino Acid Derivatives. Organic Letters 2023, 25 (25) , 4745-4749. https://doi.org/10.1021/acs.orglett.3c01760
    5. Álvaro Gutiérrez-Bonet, Wenbin Liu. Synthesis of Alkyl Fluorides and Fluorinated Unnatural Amino Acids via Photochemical Decarboxylation of α-Fluorinated Carboxylic Acids. Organic Letters 2023, 25 (3) , 483-487. https://doi.org/10.1021/acs.orglett.2c04144
    6. Martin Stinglhamer, Xheila Yzeiri, Tabea Rohlfs, Tobias Brandhofer, Constantin G. Daniliuc, Olga García Mancheño. Direct Access to Unnatural Cyclobutane α-Amino Acids through Visible Light Catalyzed [2+2]-Cycloaddition. ACS Organic & Inorganic Au 2022, 2 (6) , 496-501. https://doi.org/10.1021/acsorginorgau.2c00026
    7. Paula Oroz, Claudio D. Navo, Alberto Avenoza, Jesús H. Busto, Francisco Corzana, Gonzalo Jiménez-Osés, Jesús M. Peregrina. Towards Enantiomerically Pure Unnatural α-Amino Acids via Photoredox Catalytic 1,4-Additions to a Chiral Dehydroalanine. The Journal of Organic Chemistry 2022, 87 (21) , 14308-14318. https://doi.org/10.1021/acs.joc.2c01774
    8. Peng Ji, Jing Chen, Xiang Meng, Feng Gao, Yue Dong, Hang Xu, Wei Wang. Design of Photoredox-Catalyzed Giese-Type Reaction for the Synthesis of Chiral Quaternary α-Aryl Amino Acid Derivatives via Clayden Rearrangement. The Journal of Organic Chemistry 2022, 87 (21) , 14706-14714. https://doi.org/10.1021/acs.joc.2c02029
    9. Florence Babawale, Kathiravan Murugesan, Rok Narobe, Burkhard König. Synthesis of Unnatural α-Amino Acid Derivatives via Photoredox Activation of Inert C(sp3)–H Bonds. Organic Letters 2022, 24 (26) , 4793-4797. https://doi.org/10.1021/acs.orglett.2c01822
    10. Lisa Candish, Karl D. Collins, Gemma C. Cook, James J. Douglas, Adrián Gómez-Suárez, Anais Jolit, Sebastian Keess. Photocatalysis in the Life Science Industry. Chemical Reviews 2022, 122 (2) , 2907-2980. https://doi.org/10.1021/acs.chemrev.1c00416
    11. Daiki Kuwana, Yuma Komori, Masanori Nagatomo, Masayuki Inoue. Photoinduced Decarboxylative Radical Coupling Reaction of Multiply Oxygenated Structures by Catalysis of Pt-Doped TiO2. The Journal of Organic Chemistry 2022, 87 (1) , 730-736. https://doi.org/10.1021/acs.joc.1c02736
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    13. José A. C. Delgado, José T. M. Correia, Emanuele F. Pissinati, Márcio W. Paixão. Biocompatible Photoinduced Alkylation of Dehydroalanine for the Synthesis of Unnatural α-Amino Acids. Organic Letters 2021, 23 (13) , 5251-5255. https://doi.org/10.1021/acs.orglett.1c01781
    14. Xinmou Wang, Yuming Chen, Hongjian Song, Yuxiu Liu, Qingmin Wang. Synthesis of Unnatural α-Amino Acids via Photoinduced Decatungstate-Catalyzed Giese Reactions of Aldehydes. Organic Letters 2021, 23 (6) , 2199-2204. https://doi.org/10.1021/acs.orglett.1c00345
    15. Yi Wan, Jiajie Zhu, Qiyang Yuan, Wei Wang, Yongqiang Zhang. Synthesis of β-Silyl α-Amino Acids via Visible-Light-Mediated Hydrosilylation. Organic Letters 2021, 23 (4) , 1406-1410. https://doi.org/10.1021/acs.orglett.1c00065
    16. Olivia Zhang, Jeffrey W. Schubert. Derivatization of Amino Acids and Peptides via Photoredox-Mediated Conjugate Addition. The Journal of Organic Chemistry 2020, 85 (9) , 6225-6232. https://doi.org/10.1021/acs.joc.0c00635
    17. Pranay Kothuri, Haripriya Bhumannagari, Shravani Battula, Kolachina Rekha, Kiranmai Nayani. N ‐Protection Dependent Phosphorylation of Dehydroamino Acids to Build Unusual Phosphono‐Peptides. Chemistry – An Asian Journal 2024, 1 https://doi.org/10.1002/asia.202401244
    18. Shyamal Kanti Bera, Andrea Porcheddu. Pioneering Metal‐Free Late‐Stage C−H Functionalization Using Acridinium Salt Photocatalysis. Chemistry – A European Journal 2024, 126 https://doi.org/10.1002/chem.202402809
    19. Iva S. De Jesus, Jeimy A. C. Vélez, Emanuele F. Pissinati, Jose Tiago M. Correia, Daniel G. Rivera, Márcio W. Paixao. Recent Advances in Photoinduced Modification of Amino Acids, Peptides, and Proteins. The Chemical Record 2024, 368 https://doi.org/10.1002/tcr.202300322
    20. Guo‐Qin Wang, Ting Wang, Yue Zhang, Yuan‐Xia Zhou, Dan Yang, Pan Han, Lin‐Hai Jing. Photoredox Metal‐Free Synthesis of Unnatural β ‐Silyl‐ α ‐Amino Acids via Hydrosilylation. Chemistry – An Asian Journal 2023, 18 (24) https://doi.org/10.1002/asia.202300805
    21. David M. Kitcatt, Katie A. Scott, Elena Rongione, Simon Nicolle, Ai-Lan Lee. Direct decarboxylative Giese amidations: photocatalytic vs. metal- and light-free. Chemical Science 2023, 14 (36) , 9806-9813. https://doi.org/10.1039/D3SC03143H
    22. Mengqian Zhang, Peiyang He, Yanmei Li. Light-initiated 1,3-dipolar cycloaddition between dehydroalanines and tetrazoles: application to late-stage peptide and protein modifications. Chemical Science 2023, 14 (35) , 9418-9426. https://doi.org/10.1039/D3SC02818F
    23. Liubo Li, Yan Yao, Niankai Fu. Free Carboxylic Acids: The Trend of Radical Decarboxylative Functionalization. European Journal of Organic Chemistry 2023, 26 (21) https://doi.org/10.1002/ejoc.202300166
    24. Emanuele F. Pissinati, José A. C. Delgado, Pedro A. M. Moro, José T. M. Correia, Roberto G. S. Berlinck, Márcio W. Paixão. Expanding the Chemical Space of Non‐Proteinogenic N 4 ‐Substituted Asparagine: Racemic, Enantioenriched, and Deuterated Derivatives. European Journal of Organic Chemistry 2023, 26 (21) https://doi.org/10.1002/ejoc.202300274
    25. Oleksandr O. Grygorenko, Kostiantyn P. Melnykov, Serhii Holovach, Oleksandr Demchuk. Fluorinated Cycloalkyl Building Blocks for Drug Discovery. ChemMedChem 2022, 17 (21) https://doi.org/10.1002/cmdc.202200365
    26. Jacob R. Immel, Steven Bloom. carba ‐Nucleopeptides ( c NPs): A Biopharmaceutical Modality Formed through Aqueous Rhodamine B Photoredox Catalysis. Angewandte Chemie 2022, 134 (28) https://doi.org/10.1002/ange.202205606
    27. Jacob R. Immel, Steven Bloom. carba ‐Nucleopeptides ( c NPs): A Biopharmaceutical Modality Formed through Aqueous Rhodamine B Photoredox Catalysis. Angewandte Chemie International Edition 2022, 61 (28) https://doi.org/10.1002/anie.202205606
    28. Xia Peng, Kun Xu, Qian Zhang, Li Liu, Jiajing Tan. Dehydroalanine modification sees the light: a photochemical conjugate addition strategy. Trends in Chemistry 2022, 4 (7) , 643-657. https://doi.org/10.1016/j.trechm.2022.04.008
    29. David M. Kitcatt, Simon Nicolle, Ai-Lan Lee. Direct decarboxylative Giese reactions. Chemical Society Reviews 2022, 51 (4) , 1415-1453. https://doi.org/10.1039/D1CS01168E
    30. Alemayehu Gashaw Woldegiorgis, Zhao Han, Xufeng Lin. Chiral Phosphoric Acid‐Catalyzed Enantioselective Synthesis of Pyrazole‐Based Unnatural α‐Amino Acid Derivatives. Advanced Synthesis & Catalysis 2022, 364 (2) , 274-280. https://doi.org/10.1002/adsc.202101011
    31. Andrey Shatskiy, Markus D. Kärkäs. Photoredox-Enabled Decarboxylative Synthesis of Unnatural α-Amino Acids. Synlett 2022, 33 (02) , 109-115. https://doi.org/10.1055/a-1499-8679
    32. V. Hutskalova, C. Sparr. 15.9.4 Synthesis and Applications of Acridinium Salts (Update 2022). 2022https://doi.org/10.1055/sos-SD-115-00850
    33. Mengran Wang, Chao Wang, Yumei Huo, Xiaobo Dang, Hongxiang Xue, Liangyu Liu, Hongli Chai, Xiuling Xie, Zhixuan Li, Doudou Lu, Zhaoqing Xu. Visible-light-mediated catalyst-free synthesis of unnatural α-amino acids and peptide macrocycles. Nature Communications 2021, 12 (1) https://doi.org/10.1038/s41467-021-27086-x
    34. Mengqian Zhang, Peiyang He, Yanmei Li. Contemporary Approaches to α,β-Dehydroamino Acid Chemical Modifications. Chemical Research in Chinese Universities 2021, 37 (5) , 1044-1054. https://doi.org/10.1007/s40242-021-1307-z
    35. Sukhen Karmakar, Arundutt Silamkoti, Nicholas A. Meanwell, Arvind Mathur, Arun Kumar Gupta. Utilization of C( sp 3 )‐Carboxylic Acids and Their Redox‐Active Esters in Decarboxylative Carbon−Carbon Bond Formation. Advanced Synthesis & Catalysis 2021, 363 (15) , 3693-3736. https://doi.org/10.1002/adsc.202100314
    36. Jacob R. Immel, Maheshwerreddy Chilamari, Steven Bloom. Combining flavin photocatalysis with parallel synthesis: a general platform to optimize peptides with non-proteinogenic amino acids. Chemical Science 2021, 12 (29) , 10083-10091. https://doi.org/10.1039/D1SC02562G
    37. Shruti A. Biyani, Yuta W. Moriuchi, David H. Thompson. Advancement in Organic Synthesis Through High Throughput Experimentation. Chemistry–Methods 2021, 1 (7) , 323-339. https://doi.org/10.1002/cmtd.202100023
    38. Guangjun Bao, Peng Wang, Guofeng Li, Changjun Yu, Yiping Li, Yuyang Liu, Zeyuan He, Tiantian Zhao, Jing Rao, Junqiu Xie, Liang Hong, Wangsheng Sun, Rui Wang. 1,3‐Dipolar Cycloaddition between Dehydroalanines and C,N‐Cyclic Azomethine Imines: Application to Late‐Stage Peptide Modification. Angewandte Chemie 2021, 133 (10) , 5391-5398. https://doi.org/10.1002/ange.202012523
    39. Guangjun Bao, Peng Wang, Guofeng Li, Changjun Yu, Yiping Li, Yuyang Liu, Zeyuan He, Tiantian Zhao, Jing Rao, Junqiu Xie, Liang Hong, Wangsheng Sun, Rui Wang. 1,3‐Dipolar Cycloaddition between Dehydroalanines and C,N‐Cyclic Azomethine Imines: Application to Late‐Stage Peptide Modification. Angewandte Chemie International Edition 2021, 60 (10) , 5331-5338. https://doi.org/10.1002/anie.202012523
    40. Adam Cook, Roxanne Clément, Stephen G. Newman. Reaction screening in multiwell plates: high-throughput optimization of a Buchwald–Hartwig amination. Nature Protocols 2021, 16 (2) , 1152-1169. https://doi.org/10.1038/s41596-020-00452-7
    41. Francisco José Aguilar Troyano, Kay Merkens, Khadijah Anwar, Adrián Gómez‐Suárez. Radikal‐basierte Synthese und Modifikation von Aminosäuren. Angewandte Chemie 2021, 133 (3) , 1112-1130. https://doi.org/10.1002/ange.202010157
    42. Francisco José Aguilar Troyano, Kay Merkens, Khadijah Anwar, Adrián Gómez‐Suárez. Radical‐Based Synthesis and Modification of Amino Acids. Angewandte Chemie International Edition 2021, 60 (3) , 1098-1115. https://doi.org/10.1002/anie.202010157
    43. Kay Merkens, Francisco José Aguilar Troyano, Jonas Djossou, Adrián Gómez‐Suárez. Synthesis of Unnatural α‐Amino Acid Derivatives via Light‐Mediated Radical Decarboxylative Processes. Advanced Synthesis & Catalysis 2020, 362 (12) , 2354-2359. https://doi.org/10.1002/adsc.202000300
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    Organic Letters

    Cite this: Org. Lett. 2020, 22, 6, 2196–2200
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.orglett.0c00371
    Published February 28, 2020
    Copyright © 2020 American Chemical Society
    Request reuse permissions

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