Dr. Trevor Ellis

EDUCATION

Design, Synthesis, and Application of a New Generation of Highly Acidic Nucleophilic Glycine Equivalents

Dr. Trevor K. Ellis (Mentor)

-Amino acids (-AAs) are indispensable building blocks of life, and one of the few classes of organic compounds which garner wide recognition among laymen. Besides their primary function as structural units of peptides and proteins, they also serve countless biological functions in most living things. Thus, apart from the twenty proteinogenic/coded -AAs, hundreds of structurally varied -AAs have been found in the peptides of cell walls and capsules of numerous bacteria and fungi, as well as in various natural antibiotics. Furthermore, naturally occurring -AAs have been continually used as a ‘chiral pool’ for the preparation of a plethora of biologically and pharmacologically active compounds and are widely applied in the pharmaceutical, agrichemical, and food industries.

Tailor-made -AAs are being increasingly employed in the preparation of new synthetically modified enzymes, hormones, and immunostimulants. More recently, sterically constrained -AAs have found fundamental applications in the rational de novo design of peptides and peptidomimetics with enhanced metabolic stability and physiological functions. Despite their broad application across various scientific disciplines and specialties, the high cost of reagents and extreme reaction conditions, required by current synthetic protocols for the synthesis of -AAs, have rendered their application to many industrial processes prohibitively expensive.

Current synthetic organic methodologies offer countless approaches for the preparation of -AAs of any imaginable structural or functional complexity. However, as one can learn from recent reviews, virtually all of the methods available suffer from serious drawbacks. In fact, virtually all -AAs are currently produced on the industrial scale using biocatalytic (enzymatic) methods. Thus, even in the case of the racemate resolutions, usually plagued with low efficiency (<50% yield), enzymes are the preferred choice for providing enantiomerically pure target -AAs at a substantially lower cost compared with that from the use of any of the most-efficient synthetic asymmetric methods.

With this in mind the current focus of this research project will be the investigation of synthetic methodologies, associated with the preparation of -AAs, which are general, broadly applicable, and cost efficient. The current method of interest involves the homologation or deracemization of -AAs via the application of Ni(II) complexed amino acid Schiff’s Bases. This approach has recently demonstrated vast potential with the introduction of a new generation of Ni(II) complexes in which the framework allows for the modification of many of its physiochemical properties. Due to the flexibility of this approach various methods of symmetric or asymmetric homologation may be realized (alkylation, aldol addition, Michael addition reactions) in addition to deracemization of chiral -AAs. Of particular interest is the modification of the pKa of the -protons of the enolizable amino acid subunit. It is envisioned that this may be accomplished through manipulation of the electronic factors contributed by the phenone module (i.e. the introduction of electron withdrawing substituents on one of the aromatic rings should decrease the pKa of the protons of interest). Additional interest in this area includes the incorporation of a chiral center into the ligand framework of the complex. It is envisioned that the addition of chiral center into the complex will allow for the asymmetric synthesis of optically pure a-AAs. While previous investigations have laid the foundation for the pursuits, the focus of these investigations will be the design and synthesis of new di or tri anionic pentadentate ligands which are expected to lead toward square pyramidal metal complexes with various metal di and trivalent metal salts.

CONTACT INFORMATION

Email: trevor.ellis@swosu.edu Office Number: CPP 205-E
Phone Number: 580-774-3200

TEACHING: BASIC COURSES

CHEM 1004 Gen Chem
CHEM 1004L Gen Chem Lab
CHEM 1252 Gen Chem I Lab

TEACHING: ORGANIC CHEMISTRY

CHEM 3013/3015 Org Chem I
CHEM 3111/3015L Org Chem I Lab
CHEM 4113/4115 Org Chem II
CHEM 4021/4115L Org Chem II Lab
CHEM 4213 Advanced Organic Synthesis

OTHER ACTIVITIES

AUG 2011-AUG 2021
Chemistry Club Sponsor

RECENT PUBLICATIONS

Bergagnini-Kolev, M.; Howe, M.; Burgess, E.; Wright, P.; Hamburger, S.; Zhong, Z.; Ellis, S. B.; Ellis, T. K. Synthesis of trifluoromethyl substituted nucleophilic glycine equivalents and the investigation of their potential for the preparation of α-amino acids. Tetrahedron, 2020, 77, 131741.

Maestro, M. A.; Avecilla, F.; Sorochinsky, A. E.; Ellis, T. K.; Acena, J. L.; Soloshonok, V. A. Chiral N(H)-tBu and N(H)-Ad NiII Complexes of Glycine Schiff Bases: Deduction of a Mode of Kinetic Diastereoselectivity. European Journal of Organic Chemistry. 2014, 20, 4309.

Bergagnini, M.; Fukushi, K.; Han, J.; Shibata, N.; Roussel, C.; Ellis, T. K.; Aceña, J. L.; Soloshonok, V. A. NH-Type of chiral Ni(II) complexes of glycine Schiff base: design, structural evaluation, reactivity and synthetic application. Organic and Biomolecular Chemistry. 2014, 12, 1278.

Sorochinsky, A. E.; Ueki, H.; Acena, J. L.; Ellis, T. K.; Moriwaki, H.; Sato, T.; Soloshonok, V. A. Chemical Deracemization and (S) to (R) Interconversion of Some Fluorine – containing α-Amino Acids. Journal of Fluorine Chemistry. 2013, 152, 114-118.

Sorochinsky, A. E.; Ueki, H.; Acena, J. L.; Ellis, T. K.; Morawaki, H.; Sato, T.; Soloshonok, V. A. Chemical Approach for Interconversion of (S)- and (R)- α-Amino Acids. Organic and Biomolecular Chemistry. 2013, 27, 4503-4507.

Fu, J.; Jin, J.; Cichewicz, R. H.; Hageman, S. A.; Ellis, T. K.; Xiang, L.; Peng, Q.; Jiang, M.; Arbez, N.; Hotaline, K. Ross, C.A.; Duan, W. trans-(-)-ε-Viniferin Increases Mitochodrial Sirtuin 3 (SIRT3), Activates AMP-activated Protein Kinase (AMPK), and Protects Cells in Models of Huntington Disease. J. Biological Chemistry. 2012, 287, 24460.