Synthesis of β-Deuterated Amino Acids via Palladium-Catalyzed H/D Exchange

Sheng, Fei-Fei; Gu, Jian-Guo; Liu, Kai-Hui; Zhang, Hong-Hai

doi:10.1021/acs.joc.2c01654

Synthesis of β-Deuterated Amino Acids via Palladium-Catalyzed H/D Exchange

Journal Article · Wed Nov 16 23:00:00 EST 2022 · Journal of Organic Chemistry

DOI:https://doi.org/10.1021/acs.joc.2c01654· OSTI ID:1908081

Sheng, Fei-Fei ^[1]; Gu, Jian-Guo ^[1]; Liu, Kai-Hui ^[1]; ^[2]

Nanjing Tech University (China)
Nanjing Tech University (China); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Center for Nanophase Materials Sciences (CNMS)

Despite several synthetic approaches that have been developed for α-deuterated amino acids, the synthesis of β-deuterated amino acids has remained a challenge. Herein, we disclose a palladium catalyzed H/D exchange protocol for a β-deuterated N-protected amino amide, which can be converted to a β-deuterated amino acid simply by removal of protecting groups. Further, this protocol is highly efficient, simply manipulated, and appliable for deuterium-labeling of many amino amides. In addition, deuterium labeling of phenylalanine derivatives was also successful when pivalic acid served as an additive to promote the H/D exchange process.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); National Natural Science Foundation of China (NSFC)

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1908081

Journal Information:: Journal of Organic Chemistry, Journal Name: Journal of Organic Chemistry Journal Issue: 23 Vol. 87; ISSN 0022-3263

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

References (58)

Simple and efficient preparation of (R)- and (S)-enantiomers of ?-carbon deuterium-labelled ?-amino acids Mitulovi, Goran; L�mmerhofer, Michael; Maier, N. M. Journal of Labelled Compounds and Radiopharmaceuticals, Vol. 43, Issue 5 https://doi.org/10.1002/(SICI)1099-1344(200004)43:5<449::AID-JLCR331>3.0.CO;2-0	journal	April 2000
Afterglow Organic Light-Emitting Diode Kabe, Ryota; Notsuka, Naoto; Yoshida, Kou Advanced Materials, Vol. 28, Issue 4 https://doi.org/10.1002/adma.201504321	journal	November 2015
Cryptocatalytic 1,2-Alkene Migration in a σ-Alkyl Palladium Diene Complex Evans, Louise A.; Fey, Natalie; Lloyd-Jones, Guy C. Angewandte Chemie International Edition, Vol. 48, Issue 34 https://doi.org/10.1002/anie.200901468	journal	July 2009
On the Interpretation of Deuterium Kinetic Isotope Effects in CH Bond Functionalizations by Transition-Metal Complexes Simmons, Eric M.; Hartwig, John F. Angewandte Chemie International Edition, Vol. 51, Issue 13 https://doi.org/10.1002/anie.201107334	journal	March 2012
Nonnatural Amino Acid Synthesis by Using Carbon-Hydrogen Bond Functionalization Methodology Tran, Ly Dieu; Daugulis, Olafs Angewandte Chemie International Edition, Vol. 51, Issue 21 https://doi.org/10.1002/anie.201200731	journal	April 2012
Palladium-Catalyzed ortho -Selective CH Deuteration of Arenes: Evidence for Superior Reactivity of Weakly Coordinated Palladacycles Ma, Sandy; Villa, Giorgio; Thuy-Boun, Peter S. Angewandte Chemie International Edition, Vol. 53, Issue 3 https://doi.org/10.1002/anie.201305388	journal	November 2013
Enantiospecific CH Activation Using Ruthenium Nanocatalysts Taglang, Céline; Martínez-Prieto, Luis Miguel; del Rosal, Iker Angewandte Chemie International Edition, Vol. 54, Issue 36 https://doi.org/10.1002/anie.201504554	journal	August 2015
Iridium-Catalyzed Formyl-Selective Deuteration of Aldehydes Kerr, William J.; Reid, Marc; Tuttle, Tell Angewandte Chemie International Edition, Vol. 56, Issue 27 https://doi.org/10.1002/anie.201702997	journal	June 2017
Deuterium- and Tritium-Labelled Compounds: Applications in the Life Sciences Atzrodt, Jens; Derdau, Volker; Kerr, William J. Angewandte Chemie International Edition, Vol. 57, Issue 7 https://doi.org/10.1002/anie.201704146	journal	January 2018
C−H Functionalisation for Hydrogen Isotope Exchange Atzrodt, Jens; Derdau, Volker; Kerr, William J. Angewandte Chemie International Edition, Vol. 57, Issue 12 https://doi.org/10.1002/anie.201708903	journal	February 2018
Internal Peptide Late-Stage Diversification: Peptide-Isosteric Triazoles for Primary and Secondary C(sp³ )−H Activation Bauer, Michaela; Wang, Wei; Lorion, Mélanie M. Angewandte Chemie International Edition, Vol. 57, Issue 1 https://doi.org/10.1002/anie.201710136	journal	December 2017
Efficient Access to Deuterated and Tritiated Nucleobase Pharmaceuticals and Oligonucleotides using Hydrogen‐Isotope Exchange Palazzolo, Alberto; Feuillastre, Sophie; Pfeifer, Viktor Angewandte Chemie International Edition, Vol. 58, Issue 15 https://doi.org/10.1002/anie.201813946	journal	April 2019
Palladium‐Catalysed C(sp ³ )−H Glycosylation for the Synthesis of C‐Alkyl Glycoamino Acids Liu, Yichu; Wang, Yibing; Dai, Wenhao Angewandte Chemie International Edition, Vol. 59, Issue 9 https://doi.org/10.1002/anie.201914184	journal	January 2020
C−H Functionalization—Prediction of Selectivity in Iridium(I)‐Catalyzed Hydrogen Isotope Exchange Competition Reactions Valero, Mégane; Kruissink, Thomas; Blass, Jennifer Angewandte Chemie International Edition, Vol. 59, Issue 14 https://doi.org/10.1002/anie.201914220	journal	February 2020
Kinetic Isotope Effects in Asymmetric Reactions Giagou, Thomas; Meyer, Matthew P. Chemistry - A European Journal, Vol. 16, Issue 35 https://doi.org/10.1002/chem.201001018	journal	July 2010
Raman and Neutron Scattering Study of Partially Deuterated L-Alanine: Evidence of a Solid-Solid Phase Transition de Souza, Joelma M.; Freire, Paulo T. C.; Argyriou, Dimitri N. ChemPhysChem, Vol. 10, Issue 18 https://doi.org/10.1002/cphc.200900482	journal	December 2009
Stereoretentive H/D Exchange via an Electroactivated Heterogeneous Catalyst at sp 3 C-H Sites Bearing Amines or Alcohols : Stereoretentive H/D Exchange via an Electroactivated Heterogeneous Catalyst at sp Bhatia, Souful; Spahlinger, Greg; Boukhumseen, Nehal European Journal of Organic Chemistry, Vol. 2016, Issue 24 https://doi.org/10.1002/ejoc.201600719	journal	July 2016
Pd- and Pt-catalyzed H/D exchange methods and their application for internal MS standard preparation from a Sanofi-Aventis perspective Atzrodt, Jens; Derdau, Volker Journal of Labelled Compounds and Radiopharmaceuticals, Vol. 53, Issue 11-12 https://doi.org/10.1002/jlcr.1818	journal	September 2010
A stereoselective synthesis of α-deuterium-labelled (S)-α-amino acids O’Reilly, Elaine; Balducci, Daniele; Paradisi, Francesca Amino Acids, Vol. 39, Issue 3 https://doi.org/10.1007/s00726-010-0541-3	journal	March 2010
Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules Kopf, Sara; Bourriquen, Florian; Li, Wu Chemical Reviews, Vol. 122, Issue 6 https://doi.org/10.1021/acs.chemrev.1c00795	journal	February 2022
Development of a QuEChERS-Based Stable-Isotope Dilution LC-MS/MS Method To Quantitate Ferulic Acid and Its Main Microbial and Hepatic Metabolites in Milk Waterstraat, Martin; Hildebrand, Andreas; Rosler, Margit Journal of Agricultural and Food Chemistry, Vol. 64, Issue 45 https://doi.org/10.1021/acs.jafc.6b03318	journal	November 2016
Palladium-Catalyzed H/D Exchange Reaction with 8-Aminoquinoline as the Directing Group: Access to ortho-Selective Deuterated Aromatic Acids and β-Selective Deuterated Aliphatic Acids Zhao, Donghong; Luo, Haofan; Chen, Binhui The Journal of Organic Chemistry, Vol. 83, Issue 15 https://doi.org/10.1021/acs.joc.8b00734	journal	July 2018
Development and Scale-Up of Stereoretentive α-Deuteration of Amines Michelotti, Alessia; Rodrigues, Fabien; Roche, Maxime Organic Process Research & Development, Vol. 21, Issue 11 https://doi.org/10.1021/acs.oprd.7b00227	journal	October 2017
H–D Exchange Deuteration of Arenes at Room Temperature Sawama, Yoshinari; Nakano, Akihiro; Matsuda, Takumi Organic Process Research & Development, Vol. 23, Issue 4 https://doi.org/10.1021/acs.oprd.8b00383	journal	February 2019
Mesoionic Carbene–Iridium Complex Catalyzed Ortho -Selective Hydrogen Isotope Exchange of Anilines with High Functional Group Tolerance Liu, Wei; Cao, Lei; Zhang, Zengyu Organic Letters, Vol. 22, Issue 6 https://doi.org/10.1021/acs.orglett.0c00402	journal	March 2020
Synthesis of Multideuterated (Hetero)aryl Bromides by Ag(I)-Catalyzed H/D Exchange Hu, Guang-Qi; Bai, Jing-Wen; Li, En-Ci Organic Letters, Vol. 23, Issue 5 https://doi.org/10.1021/acs.orglett.0c04139	journal	February 2021
Selective α-Deuteration of Amines and Amino Acids Using D ₂ O Chatterjee, Basujit; Krishnakumar, Varadhan; Gunanathan, Chidambaram Organic Letters, Vol. 18, Issue 22 https://doi.org/10.1021/acs.orglett.6b02978	journal	November 2016
C–H Functionalization of N-Methylated Amino Acids and Peptides as Tool in Natural Product Synthesis: Synthesis of Abyssenine A and Mucronine E Kinsinger, Thorsten; Kazmaier, Uli Organic Letters, Vol. 20, Issue 23 https://doi.org/10.1021/acs.orglett.8b03475	journal	November 2018
Palladium-Catalyzed Remote meta -C–H Bond Deuteration of Arenes Using a Pyridine Template Xu, Hui; Liu, Min; Li, Ling-Jun Organic Letters, Vol. 21, Issue 12 https://doi.org/10.1021/acs.orglett.9b01784	journal	June 2019
Ag ₂ CO ₃ -Catalyzed H/D Exchange of Five-Membered Heteroarenes at Ambient Temperature Li, En-Ci; Hu, Guang-Qi; Zhu, Yu-Xing Organic Letters, Vol. 21, Issue 17 https://doi.org/10.1021/acs.orglett.9b02369	journal	August 2019
Biocatalytic, Stereoselective Deuteration of α-Amino Acids and Methyl Esters Chun, Stephanie W.; Narayan, Alison R. H. ACS Catalysis, Vol. 10, Issue 13 https://doi.org/10.1021/acscatal.0c01885	journal	June 2020
Site-Selective Silver-Catalyzed C–H Bond Deuteration of Five-Membered Aromatic Heterocycles and Pharmaceuticals Tlahuext-Aca, Adrian; Hartwig, John F. ACS Catalysis, Vol. 11, Issue 3 https://doi.org/10.1021/acscatal.0c04917	journal	January 2021
Cobalt-Catalyzed Stereoretentive Hydrogen Isotope Exchange of C(sp ³ )–H Bonds Palmer, W. Neil; Chirik, Paul J. ACS Catalysis, Vol. 7, Issue 9 https://doi.org/10.1021/acscatal.7b02051	journal	August 2017
Experimental and Computational Studies on Remote γ-C(sp³)–H Silylation and Germanylation of Aliphatic Carboxamides Deb, Arghya; Singh, Sukriti; Seth, Kapileswar ACS Catalysis, Vol. 7, Issue 12 https://doi.org/10.1021/acscatal.7b03056	journal	November 2017
Hydrogen/Deuterium (H/D) Exchange Catalysis in Alkanes Sattler, Aaron ACS Catalysis, Vol. 8, Issue 3 https://doi.org/10.1021/acscatal.7b04201	journal	January 2018
Site-Selective Nickel-Catalyzed Hydrogen Isotope Exchange in N -Heterocycles and Its Application to the Tritiation of Pharmaceuticals Yang, Haifeng; Zarate, Cayetana; Palmer, W. Neil ACS Catalysis, Vol. 8, Issue 11 https://doi.org/10.1021/acscatal.8b03717	journal	September 2018
Ruthenium-Catalyzed Selective α,β-Deuteration of Bioactive Amines Neubert, Lorenz; Michalik, Dirk; Bähn, Sebastian Journal of the American Chemical Society, Vol. 134, Issue 29 https://doi.org/10.1021/ja3041338	journal	July 2012
Stereoselective Synthesis of β-Alkylated α-Amino Acids via Palladium-Catalyzed Alkylation of Unactivated Methylene C(sp³)–H Bonds with Primary Alkyl Halides Zhang, Shu-Yu; Li, Qiong; He, Gang Journal of the American Chemical Society, Vol. 135, Issue 32 https://doi.org/10.1021/ja406484v	journal	August 2013
Ligand-Enabled β-C–H Arylation of α-Amino Acids Using a Simple and Practical Auxiliary Chen, Gang; Shigenari, Toshihiko; Jain, Pankaj Journal of the American Chemical Society, Vol. 137, Issue 9 https://doi.org/10.1021/ja512690x	journal	March 2015
Site-Selective Deuteration of Amino Acids through Dual-Protein Catalysis Doyon, Tyler J.; Buller, Andrew R. Journal of the American Chemical Society, Vol. 144, Issue 16 https://doi.org/10.1021/jacs.2c00608	journal	April 2022
Lipidomics Reveals Dramatic Physiological Kinetic Isotope Effects during the Enzymatic Oxygenation of Polyunsaturated Fatty Acids Ex Vivo Navratil, Aaron R.; Shchepinov, Mikhail S.; Dennis, Edward A. Journal of the American Chemical Society, Vol. 140, Issue 1 https://doi.org/10.1021/jacs.7b09493	journal	December 2017
Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design Meanwell, Nicholas A. Journal of Medicinal Chemistry, Vol. 54, Issue 8 https://doi.org/10.1021/jm1013693	journal	April 2011
Using Deuterium in Drug Discovery: Leaving the Label in the Drug Gant, Thomas G. Journal of Medicinal Chemistry, Vol. 57, Issue 9 https://doi.org/10.1021/jm4007998	journal	December 2013
Carbon–Deuterium Bonds as Probes of Protein Thermal Unfolding Yu, Wayne; Dawson, Phillip E.; Zimmermann, Jörg The Journal of Physical Chemistry B, Vol. 116, Issue 22 https://doi.org/10.1021/jp303521t	journal	May 2012
Synthesis of Deuterated Benzopyran Derivatives as Selective COX-2 Inhibitors with Improved Pharmacokinetic Properties Zhang, Yanmei; Tortorella, Micky D.; Wang, Yican ACS Medicinal Chemistry Letters, Vol. 5, Issue 10 https://doi.org/10.1021/ml500299q	journal	August 2014
Novel Acetoxylation and C−C Coupling Reactions at Unactivated Positions in α-Amino Acid Derivatives Reddy, B. V. Subba; Reddy, Leleti Rajender; Corey, E. J. Organic Letters, Vol. 8, Issue 15 https://doi.org/10.1021/ol061389j	journal	June 2006
The isotopic effects of deuteration on optoelectronic properties of conducting polymers Shao, Ming; Keum, Jong; Chen, Jihua Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms4180	journal	January 2014
Heavy drugs draw heavy interest from pharma backers Katsnelson, Alla Nature Medicine, Vol. 19, Issue 6 https://doi.org/10.1038/nm0613-656	journal	June 2013
Isotope effect in spin response of π-conjugated polymer films and devices Nguyen, Tho D.; Hukic-Markosian, Golda; Wang, Fujian Nature Materials, Vol. 9, Issue 4 https://doi.org/10.1038/nmat2633	journal	February 2010
Geometric isotope effect of deuteration in a hydrogen-bonded host–guest crystal Shi, Chao; Zhang, Xi; Yu, Chun-Hua Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-018-02931-8	journal	February 2018
Bringing biocatalytic deuteration into the toolbox of asymmetric isotopic labelling techniques Rowbotham, J. S.; Ramirez, M. A.; Lenz, O. Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-020-15310-z	journal	March 2020
γ-Selective C(sp3)–H amination via controlled migratory hydroamination Lee, Changseok; Seo, Huiyeong; Jeon, Jinwon Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-25696-z	journal	September 2021
Palladium-catalyzed Br/D exchange of arenes: selective deuterium incorporation with versatile functional group tolerance and high efficiency Zhang, Hong-Hai; Bonnesen, Peter V.; Hong, Kunlun Organic Chemistry Frontiers, Vol. 2, Issue 9 https://doi.org/10.1039/C5QO00181A	journal	January 2015
Cascade alkylation and deuteration with aryl iodides via Pd/norbornene catalysis: an efficient method for the synthesis of congested deuterium-labeled arenes Guo, Lei; Xu, Chen; Wu, Ding-Chuan Chemical Communications, Vol. 55, Issue 59 https://doi.org/10.1039/C9CC03988K	journal	January 2019
Ag( i )-Mediated hydrogen isotope exchange of mono-fluorinated (hetero)arenes Hu, Guang-Qi; Li, En-Ci; Zhang, Hong-Hai Organic & Biomolecular Chemistry, Vol. 18, Issue 34 https://doi.org/10.1039/D0OB01273D	journal	January 2020
Silver-catalyzed regioselective deuteration of (hetero)arenes and α-deuteration of 2-alkyl azaarenes Dong, Baobiao; Cong, Xuefeng; Hao, Na RSC Advances, Vol. 10, Issue 43 https://doi.org/10.1039/D0RA02358B	journal	January 2020
Photoredox-catalyzed deuteration and tritiation of pharmaceutical compounds Loh, Yong Yao; Nagao, Kazunori; Hoover, Andrew J. Science, Vol. 358, Issue 6367 https://doi.org/10.1126/science.aap9674	journal	November 2017
Efficient and Selective Pt/C-Catalyzed H–D Exchange Reaction of Aromatic Rings Ito, Nobuhiro; Esaki, Hiroyoshi; Maesawa, Tsuneaki Bulletin of the Chemical Society of Japan, Vol. 81, Issue 2 https://doi.org/10.1246/bcsj.81.278	journal	February 2008

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
amides
catalysts
hydrogen isotopes
monomers
peptides and proteins

Synthesis of β-Deuterated Amino Acids via Palladium-Catalyzed H/D Exchange

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