Hien Nguyen

Hien Nguyen

Research interest(s)/area of expertise

Medicinal chemistry, chemical biology, organic chemistry, cancer drug discovery, vaccine adjuvant immunotherapy, Alzheimer's disease, diabetes, catalytic stereoselective carbohydrate methods, transition-metal catalysis.

Research

Hien M. Nguyen was born in Ho Chi Minh City (Saigon), Vietnam. Prof. Nguyen came to the US in 1989 and first settled with his family in Boston, Massachusetts. He graduated with honors from Tufts University in Medford, Massachusetts where he majored in chemistry and conducted research with Professor Marc d'Alarcao. Hien left Boston and moved to attend the University of Illinois at Urbana-Champaign and he subsequently joined the group of the late David Y. Gin. His Ph.D. thesis focused on developing new carbohydrate methodologies for efficient assembly of complex oligosaccharides. As an NIH postdoctoral fellow in the group of Prof. Barry Trost at Stanford University, Prof. Nguyen pursued training in the area of transition-metal catalysis. Prof. Nguyen began his independent career in 2006 and was promoted with tenure at the University of Iowa. In 2018, he relocated to Wayne State University as the Carl Johnson/Pfizer endowed chair and professor of chemistry.

The overarching goal of Prof. Nguyen's research program is to identify novel targets that can be utilized for vaccine adjuvant cancer immunotherapy as well as for the treatment of multiple myeloma (MM), pancreatic ductal adenocarcinoma (PDAC), metastatic breast cancer, diabetes, and Alzheimer’s disease (AD). The molecules we discover are identified through diverse approaches, including the synthesis and isolation of natural saponin adjuvants, the derivatization of readily available aminoglycosides, and the synthesis of diverse oligosaccharide compounds, all supported by computational insights. Throughout the process, we often develop novel methods for the assembly of oligosaccharides, glycopeptides, and pharmaceuticals containing fluorine and amine functionalities, in addition to conducting biological assays, which often need to be developed. These efforts substantially expand the application of chemistry in the discovery of new therapies aimed at improving human health.

Education

• B.S., Tufts University, 1996
• Ph.D., University of Illinois at Urbana-Champaign, 2003
• NIH Postdoctoral Fellow, Stanford University, 2003 - 2006

Awards and grants

• R01GM098285 (06/01/2019 - 05/31/2025) "Tailoring Structure of Sulfated Oligosaccharides for Modulating Heparanase Activity"
• R01GM136968 (04/01/2020 - 03/31/2024) "Strategies for Expedited Synthesis of Sulfated Aminoglycans"
• R01AI169505 (06/01/2022 - 05/31/2027) "Synthesis and Evaluation of Carbohydrate Vaccine Adjuvants"
• R35GM149213 (09/01/2023 - 08/31/2018) "Development of Catalytic Glycosylations and Biologically Important Glycosaminoglycans"

Selected publications

• Ghorai, J.; Almounajed, L.; Noori, S. Nguyen, H. M. "Cooperative Catalysis in Stereoselective O- and N-Glycosylations with Glycosyl Trichloroacetimidates Mediated by Singly Protonated Phenanthrolinium Salt and Trichloroacetamide" J. Am. Chem. Soc. 2024, 146, 34413-34426
• Wakpal, J.; Pathiranage, P.; Walker, A.; Nguyen, H. M. "Rational Design and Expedient Synthesis of Heparan Sulfate Mimetics from Natural Aminoglycosides for Structure and Activity Relationship Studies" Angew. Chem. Int. Ed. 2023, 62, e2020304325
• Usman, F.; Gogoi, A. R.; Mixdorf, J. C.; Gutierrez, O.; Nguyen, H. M. "Rhodium-Catalyzed Asymmetric Synthesis of 1,2-Disubstituted Allylic Fluorides." Angew. Chem. Int. Ed. 2023, 62, e202314843
• Rodrigo, S.; Hazra, A.; Mahajan, J. P.; Nguyen, H. M.; Luo, L. "Overcoming the Potential Window-Limited Functional Group Compatibility by Alternating Current Electrolysis." J. Am. Chem. Soc. 2023, 145, 21851-21859
• Arachchi, M. K.; Schaugaard, R. N.; Schlegel, H. B.; Nguyen, H. M. "Asymmetric Synthesis of alpha-Trisubstituted-alpha-Tertiary Amines via Rhodium-Catalysis." J. Am. Chem. Soc. 2023, 145, 19642-19654
• Abdulsalam, H.; Li, J.; Loka, R. S.; Sletten, E. T.; Nguyen, H. M. "Heparan Sulfate Mimicking Glycopolymers Bind SARS-CoV-2 Spike Protein in a Length and Sulfation Pattern Dependent Manner" ACS Med. Chem. Lett. 2023, 14, 1411-1418
• Li, J.; Nguyen, H. M. "Phenanthroline Catalysis in Stereoselective 1,2-cis Glycosylations." Acc. Chem. Res. 2022, 55, 3738-3751
• Loka, R. S.; Song, Z.; Sletten, E. T.; Kayal, Y.; Vlodavsky, I.; Zhang, K.; Nguyen, H. M. "Heparan Sulfate-Like Glycopolymer Prevents Pancreatic Beta Cell Destruction and Suppresses Islet Inflammation under the Challenge of Upregulated Heparanase." ACS Chem. Biol. 2022, 17, 1387-1400
• Xu, H.; Schaugaard, R. N.; Li, J.; Schlegel, H. B.; Nguyen, H. M. "Phenanthroline-Catalyzed Stereoselective 1,2-cis Furanosylations." J. Am. Chem. Soc. 2022, 144, 7441-7456
• Arachchi, M. K.; Nguyen, H. M. "Iridium-Catalyzed Enantioselective Allylic Substitutions of Racemic Branched Trichloroacetimidates with Hetereoatom Nucleophiles." Adv. Synth. Catal. 2021, 363, 4239-4246
• Schaugaard, R. N.; Nguyen, H. M.; Schlegel, H. B. "Alkyl Radical-Free Cu(II) Photocatalytic Cross-Coupling: A Theoretical Study of Anomerically Specific Photocatalyzed Glycosylation of Pyranosyl Bromide." Inorg. Chem. 2021, 60, 12801-12812
• Li, J.; Nguyen, H. M. "A Mechanistic Probe into 1,2-cis Glycoside Formation Catalyzed by Phenanthroline and Further Expansion of Scope." Adv. Synth. Catal. 2021, 363, 4054-4066
• DeMent, P. M.; Lu, C.; Wakpal, J.; Schaugaard, R. N.; Schlegel, H. B.; Nguyen, H. M. "Phenanthroline-Catalyzed Stereoselective Formation of alpha-1,2-cis-2-Deoxy-2-Fluoro Glycosides." ACS Catalysis, 2021, 11, 2108-2120
• Vlodavsky, I.; Barash, U.; Nguyen, H. M.; Yang, S.-M.; Ilan, N. "Biology of Heparanase-Heparan Sulfate Axis and Its Role in Disease Pathogenesis." Sem. Thromosis Hemostasis 2021, 47, 240-253
• Zhu, S.; Li, J.; Loka, R. S.; Vlodavsky, I.; Zhang, K.; Nguyen, H. M. “Modulating Heparanase Activity: Tuning Sulfation Pattern and Glycosidic Linkage of Oligosaccharides” J. Med. Chem. 2020, 63, 4227-4255
• Zhang, K.; Liu, H.; Song, Z.; Jiang, Y.; Kim, H.; Samavati, L.; Nguyen, H. M.; Yang, Z.-Q. "The UPR Trasducer IRE1 Promotes Breast Cancer Malignancy by Degrading Tumor Suppressor microRNAs." iScience 2020, 23, 101503
• Rodrigo, S.; Um, C.; Mixdorf, J. C.; Gunasekera, D.; Nguyen, H. M.; Long, L. "Alternating Current Electrolysis for organic Electrosynthesis: Trifluoromethylation of (Hetero)arenes." Org. Lett. 2020, 22, 6719-6723
• Yu, F.; Dickson, J. L.; Loka, R. S.; Xu, H.; Schaugaard, R. N.; Schlegel, H. B.; Luo, L.; Nguyen, H. M. "Diastereoselective sp3 C-O Bond Formation via Visible Light-Induced Copper-Catalyzed Cross Couplings of Anomeric Alkyl Bromides with Aliphatic Alcohols." ACS Catalysis, 2020, 10, 5990-6001
• Sorlin, A. M.; Fuad, U. O.; English, C. K.; Nguyen, H. M. "Advances in Nucleophilic Allylic Fluorination." ACS Catalysis 2020, 10, 11980-12010
• Loka, R. S.; Sletten, E. T.; Barash, U.; Vlodavsky, I.; Nguyen, H. M. “Specific Inhibition of Heparanase by Glycopolymer with Well-Defined Sulfation Pattern Prevents Breast Cancer Metastasis in Mice.” ACS Appl. Mater. Interfaces 2019, 11, 244-254
• Yu, F.; Li, J.; DeMent, P. M.; Tu, Y.-J.; Schlegel, H. B.; Nguyen, H. M. “Phenanthroline-Catalyzed Stereoselective Glycosylations.” Angew. Chem. Int. Ed. 2019, 58, 6957-6961
• Sletten, E. T.; Tu, Y.-T.; Schlegel, H. B.;* Nguyen, H. M.* “Are Brønsted Acids the True Promoter of Metal Triflate Catalyzed Glycosylations? A Mechanistic Probe into 1,2-cis-Aminoglycoside Formation by Nickel Triflate.” ACS. Catalysis 2019, 9, 2110-2123
• Zhu, S.; Samala, G.; Sletten, E. T.; Stockdill, J. L.; Nguyen, H. M. “Facile Triflic Acid-Catalyzed a-1,2-cis-Thiol Glycosylations: Scope and Application to the Synthesis of S-Linked Oligosaccharides, Glycolipids, Sublancin Glycopeptides, and TN/TF Antigens.” Chem. Sci. 2019, 10, 10475-10480
• Sorlin, A. M.; Mixdorf, J. C.; Rotella, M.; Martin, R.; Gutierrez, O.; Nguyen, H. M. “The Role of Trichloroacetimidate to Enable Irididium-Catalyzed Regio- and Enantioselective Allylic Fluorination.” J. Am. Chem. Soc. 2019, 143, 14843-14882
• Mixdorf, J. C; Sorlin, A. M.; Dick, D.; Nguyen, H. M. “Iridium-Catalyzed Radiosynthesis of Branched Allylic [18F]Fluorides.” Org. Lett. 2019, 21, 60-64

Courses taught by Hien Nguyen

Winter Term 2025 (current)

• CHM6220 - Organic Reactions and Synthesis
• CHM7220 - Organic Reactions and Synthesis

Fall Term 2024

• CHM6200 - Organic Structures and Mechanisms
• CHM7200 - Organic Structures and Mechanisms

Winter Term 2024

• CHM6220 - Organic Reactions and Synthesis
• CHM7220 - Organic Reactions and Synthesis

Fall Term 2023

• CHM5510 - Chemical Synthesis Laboratory

Winter Term 2023

• CHM4850 - Frontiers in Chemistry
• CHM6220 - Organic Reactions and Synthesis
• CHM7220 - Organic Reactions and Synthesis
• CHM8850 - Frontiers in Chemistry