Campus Ring 1, 28759 Bremen, Germany
The Nugent group is interested in the synthesis of organic molecules of consequence, that is, those having an immediate societal impact (pharmaceutical and natural product drugs) and those containing challenging architectural features. These molecules require many chemical operations to synthesize (build) them and sometimes require years of research to do so.
More often than not, a specific sequence of chemical operations (multistep organic synthesis) may only be accomplished when new synthetic methods (single organic transformations) are developed. In particular synthetic methods based on enantioselective catalysis, employing transition metals (organometallic catalysts) or organic catalysts, are at the forefront of our modern know-how in synthetic organic chemistry.
Development of these reactions is important because they enable the transformation of inexpensive prochiral (i.e. without handedness) organic starting materials into high value chiral (i.e. with handedness) synthons. These chiral synthons (building blocks) allow the efficient synthesis of pharmaceutical and natural product drugs to occur and are consequently a major focus of our research efforts.
Current Research:
In Water Reaction Concepts
Ø Control of imine formation capabilities for in water reactions (2021)
Ø First aldol over Knoevenagel chemoselectivity (2021)
Ø Cucurbituril based host-guest reaction rate acceleration (2021)
Enantioselective Organocatalysis
- Enamine based bifunctional catalyst concepts (2017)
¡ Salt bridge transition state organizing principles
¡ Hydrogen bond transition state organizing principles
- Site-Selectivity within tri- and diketones (2016 and 2021)
¡ Highly selective mono-aldolization
¡ Desymmetrization
¡ Access to new aldol diastereomers
- Michael substrate expansion: tolerance to acidic spectator functional groups (2017)
¡ Carboxylic acids
¡ Aniline-based amides
¡ Catechols and phenols
Natural Product/Pharmaceutical Drug Synthesis
- First enantioselective synthesis of a class of Alzheimer research drugs (2016)
¡ γ-secretase modulators
² Highest yielding synthesis of Merck Sharp & Dohme’s top research drug candidate
² Medicinal chemistry opportunities
¡ β-secretase modulator (current pursuit)
- Step efficient synthesis (2017)
¡ Shortest enentioselective synthesis of (R)-Pristiq (commercial anti-depressive)
Asymmetric Chiral Amine Synthesis
- Reductive Amination – Primary Amine Synthesis
¡ Ketone to Primary Amine in two reaction steps
¡ Ytterbium based methods allowing increased stereoselectivity
¡ Titanium based methods allowing increased ketone substrate breadth
- Carbanion based Primary Amine Synthesis
¡ One-pot imine formation and carbanion addition method
| 1990 | B.Sc. in Chemistry, Virginia Polytechnic Institute & State University, Blacksburg, Virginia, USA |
|---|---|
| 1995 | Ph.D. in Organic Chemistry, Virginia Polytechnic Institute & State University, Blacksburg, Virginia, USA |
| 1996-1997 | Postdoctoral Fellow, University of Liverpool, Liverpool, Great Britain |
- Postdoctoral fellowship, University of Liverpool, Liverpool, Great Britain (1996-1997)
- Professor's Social Involvement Award (Student governmentt awarded in 2005)
- Teacher of the Year 2016 (within the Natural Science programs)
- Teacher of the Year 2020 (within the Natural Science programs)
- Process Research Chemist, Catalytica Fine Chemicals / DSM Pharmaceuticals, Mountain View, California, USA (1998-2000)
- Process Research Chemist, Pharmacia / Pfizer Corporation, South San Francisco, California, USA (2001-2003)
- Assistant Professor of Organic Chemistry, International University of Bremen, Bremen, Germany (January 2004)
- Associate Professor of Organic Chemistry, Jacobs University Bremen gGmbH, Bremen, Germany (September 2017)
Taught Courses:
Since February 2018 I am the Study Program Coordinator for the Medicinal Chemistry & Chemical Biology B. Sc. program.
Courses taught yearly since 2018:
Medicinal Chemistry & Chemical Biology (7.5 ECTS)
General Organic Chemistry (5.0 ECTS)
Advanced Organic Chemistry (5.0 ECTS)
Advanced Organic Synthesis (5.0 ECTS, taught every other year)
Seminar (Presentation Course, 2.5 ECTS, discontinued starting Spring 2022)
Book (editor)
- Chiral Amine Synthesis. Methods, Developments and Applications; Nugent, T. C. Ed.; Wiley-VCH: Weinheim, 2010.
Book Chapters
- Nugent, T. C. Asymmetric Reductive Amination. In Chiral Amine Synthesis. Methods, Developments and Applications, Nugent, T. C. Ed.; Wiley-VCH: Weinheim, 2010, p. 225-245.
- Nugent, T. C. Chiral Amine Synthesis – Strategies, Examples, and Limitations. In Process Chemistry in the Pharmaceutical Industry, Second Edition: Challenges in an Ever-Changing Climate, Braish, T. F.; Gadamasetti, K. Eds.; CRC Press-Taylor and Francis Group: New York, 2008, p. 137-156.
Manuscripts
- Invited contribution to a Special Collection on ‘Organocatalysis’:
T. C. Nugent*, A. E. de Vos, I. Hussain, H. A. E. D. Hussein, A 2000 to 2020 Practitioner’s Guide to Chiral Amine Based Enantioselective Aldol Reactions: Ketone Substrates, Best Methods, in Water Reaction Environments, and Defining Nuances,
Eur. J. Org. Chem. 2022, e202100529. (EurJOC no longer has page numbers, instead an eLocator).
https://doi.org/10.1002/ejoc.202100529 - F. N. Tehrani, K. I. Assaf, * R. Hein, Casper M. E. Jensen, T. C. Nugent, W. M. Nau, *Supramolecular Catalysis of a Catalysis-Resistant Diesl-Alder Reaction: Almost Theoretical Acceleration of Cyclopentadiene Dimerization inside Cucurbit [7]uril,
ACS Catalysis2022, 12, 2061-2269
https://doi.org/10.1021/acsatal.1c05659 - T. C. Nugent*, F. Goswami, S. Debnath, I. Hussain, H. A. E. D. Hussein, A. Karn, and S. Nakka, Harnessing Additional Capability from in Water Reaction Conditions: Aldol versus Knoevenagel Chemoselectivity,
Adv. Synth. Catal. 2021, 363, 3539 – 3545.
https://doi.org/10.002/adsc.202100301 - A. Sadiq and T. C. Nugent*, Catalytic Access to Succinimide Products Containing Stereogenic Quaternary Carbons,
ChemistrySelect 2020, 5, 11934 – 11938.
https://doi.org/10.1002/slct.202003664 - T. C. Nugent*, H. A. E. D. Hussein, S. Ahmed, F. T. Najafian, I. Hussain, T. Georgiev, M. K. Al-Joumhawy, Carboxylate Salt Bridge-Mediated Enamine Catalysis: Expanded Michael Reaction Substrate Scope and Facile Access to Antidepressant (R)-Pristiq,
Adv. Synth. Catal. 2017, 359, 2824–2831.
https://doi.org/10.1002/adsc.201700801 - T. C. Nugent*, P. Spiteller, I. Hussain, H. A. E. D. Hussein, F. T. Najafian, A Catalyst-Directed Remote Stereogenic Center Switch During the Site-Selective Aldol Desymmetrization of Cyclohexanone-Based Diketones,
Adv. Synth. Catal. 2016, 358, 3706-3713.
https://doi.org/10.1002/adsc.201600833 - T. C. Nugent*, F. T. Najafian, H. A. E. D. Hussein, I. Hussain, Beyond Chemoselectivity: Catalytic Site-Selective Aldolization of Diketones and Exploitation for Enantioselective Alzheimer Drug Candidate Synthesis,
Chem. Eur. J. 2016, 22, 14342-14348.
https:/doi.org/10.1002/chem.201602900 - T. C. Nugent*, R. V. Williams*, A. Dragan, A. A. Méndez, A. V. Iosub, An investigation of the observed, but counterintuitive, stereoselectivity noted during chiral amine synthesis via N-chiral-ketimines,
Beilstein J. Org. Chem. 2013, 9, 2103-2112. - T. C. Nugent*, S. M. Marinova, Step Efficient Access to Chiral Primary Amines,
Synthesis 2013, 45, 153-166. - T. C. Nugent*, A. Bibi, A. Sadiq, M. Shoaib, M. N. Umar, F. N. Tehrani, Chiral Picolylamines for Michael and Aldol Reactions: Probing Substrate Boundaries,
Org. Biomol. Chem. 2012, 10, 9287-9294. - T. C. Nugent*, A. Sadiq, A. Bibi, T. Heine, L. L. Zeonjuk N. Vankova, B. S. Bassil, Noncovalent Bifunctional Organocatalysts: Powerful Tools for Contiguous Quaternary-Tertiary Stereogenic Carbon Formation, Scope, and Origin of Enantioselectivity,
Chem. Eur. J. 2012, 18, 4088-4098. - T. C. Nugent*, D. E. Negru, M. El-Shazly, D. Hu, A. Sadiq, A. Bibi, M. N. Umar, Sequential Reductive Amination-Hydrogenolysis: A One-Pot Synthesis of Challenging Chiral Primary Amines,
Adv. Synth. & Catal. 2011, 353, 2085-2092. - T. C. Nugent*, M. Shoaib, A. Shoaib, Practical access to highly enantioenriched quaternary carbon Michael adducts using simple organocatalysts, Org. Biomol. Chem. 2011, 9, 52-56.
- T. C. Nugent*, M. N. Umar, A. Bibi, Picolylamine as an Organocatalyst Template for Highly Diastereo- and Enantioselective Aqueous Aldol Reactions, Org. Biomol. Chem. 2010, 8, 4085-4089.
- T. C. Nugent*, M. El-Shazly, Chiral Amine Synthesis – Recent Developments and Trends for Enamide Reduction, Reductive Amination, and Imine Reduction, Adv. Synth. & Catal. 2010, 352, 753-819.
- T. C. Nugent*, M. El-Shazly, V. N. Wakchaure, Ytterbium Acetate Promoted Asymmetric Reductive Amination: Significantly Enhanced Stereoselectivity,
J. Org. Chem. 2008, 73, 1297-1305. - T. C. Nugent*, A. Ghosh, Selective Synthesis of Unnatural a-, b-, and g-Amino Esters,
Eur. J. Org. Chem. 2007, 3863-3869. - V. N. Wakchaure, R. R. Mohanty, A. J. Shaikh, T. C. Nugent*, A One-Pot Asymmetric Sequential Amination-Alkylation Reaction: Expedient Synthesis of a-Alkyl,-Alkyl Substituted Chiral Amines,
Eur. J. Org. Chem. 2007, 959-964. - T. C. Nugent*, A. K. Ghosh, V. N. Wakchaure, R. R. Mohanty, Asymmetric Reductive Amination: Convenient Access to Enantioenriched Alkyl-Alkyl or Aryl-Alkyl Substituted a-Chiral Primary Amines,
Adv. Synth. & Catal. 2006, 348, 1289-1299. - T. C. Nugent*, R. Seemayer, An Efficient Enantiopure Synthesis of a Pivotal Precursor to Substance P Antagonists,
Org. Process Res. Dev. 2006, 10, 142-148. - T. C. Nugent*, V. N. Wakchaure, A. K. Ghosh, R. R. Mohanty, Evolution of Ti(OiPr)4 and Raney-Nickel for the Asymmetric Reductive Amination of Prochiral Ketones,
Org. Lett. 2005, 7, 4967-4970. - J. J. Chen*, T. C. Nugent, C. V. Lu, S. Kondapally, P. Giannousis, Y. Wang, J. T. Wilmot, Rapid Improvement of a Reductive Sulfonylation Using Design of Experiment Methods,
Org. Process Res. Dev. 2003, 7, 313-317. - T. C. Nugent, T. Hudlicky*, Chemoenzymatic Synthesis of all Four Stereoisomers of Sphingosine from Chlorobenzene: Glycosphingolipid Precursors,
J. Org. Chem. 1998, 63, 510-520. - B. M. Adger, J. V. Barkley, S. Bergeron, M. W. Cappi, B. E. Flowerdew, M. P. Jackson, R. McCague, T. C. Nugent, S. M. Roberts*, Improved Procedure for Juliá-Colonna Asymmetric Epoxidation of a, b-Unsaturated Ketones: Total Synthesis of Diltiazem and Taxol Side Chain,
J. Chem. Soc., Perkin Trans. 1 , 1997, 3501-3507. - P. A. Bentley, S. Bergeron, M. W. Cappi, D. E. Hibbs, M. B. Hursthouse, T. C. Nugent, R. Pulido, S. M. Roberts*, Asymmetric Epoxidation of Enones Employing Polymeric a-Amino Acids in Non-Aqueous Media,
J. Chem. Soc., Chem. Commun. 1997, 739-740. - M. G. Banwell, N. Haddad, T. Hudlicky*, T. C. Nugent, M. F. Mackay, S. L. Richard, Regio- and Stereo-Chemical Outcomes in the Nucleophilic Ring Cleavage Reactions of Monoepoxides Derived from cis-1,2-Dihydrocatechols,
J. Chem. Soc., Perkin Trans. 1, 1997, 1779-1791. - T. Hudlicky*, T. C. Nugent, W. Griffith, Chemoenzymatic Synthesis of D-erythro-C18- and L-threo-C18-sphingosines,
J. Org. Chem. 1994, 59, 7944-7946. - T. Hudlicky*, M. G. Natchus, T. C. Nugent, Improved Practical Synthesis of a Prostaglandin and Carbocyclic Nucleoside Synthon,
Synth. Comm., 1992, 22, 151-157. Citations: 15 (Scopus) - T. Hudlicky*, H. Luna, H. F. Olivo, C. Anderson, T. C. Nugent, J. D. Price, Biocatalysis as a Strategy in the Exhaustive Enantiocontrolled Synthesis of Conduritols,
J. Chem. Soc., Perkin Trans. 1, 1991, 2907-2917.
- American Chemical Society (ACS)
- Gesellschaft Deutscher Chemiker (GDCh)