Christopher Hulme

Professor, Pharmacology and Toxicology

Professor, BIO5 Institute

Primary Department

Pharmacology and Toxicology

Department Affiliations

Pharmacology and Toxicology

Contact

(520) 626-5322

hulme@arizona.edu

Work Summary

The Hulme group is focused on small molecule drug design and developing enabling chemical methodologies to expedite the drug discovery process. The development of small molecule inhibitors of kinases is of particular interest.

Research Interest

Christopher Hulme, PhD, focuses on small molecule drug design and developing enabling chemical methodologies to expedite the drug discovery process. Target families of particular current interest for the group are kinases, protein-protein interactions and emerging DNA receptors for indications in oncology. Such efforts are highly collaborative in nature and students will be exposed to the full array of design hurdles involved in progressing molecules along the value chain to clinical evaluation. These efforts will be aided by the group’s interest in both microwave assisted organic synthesis (MAOS) and flow chemistry. Both technologies enable ‘High-throughput Medicinal Chemistry’ (HTMC) and will be supported by similar High-throughput Purification capabilities.The group also has a long standing interest in the development of new reactions that produce biologically relevant molecules in an efficient manner. Front loading screening collections with molecules possessing high ‘iterative efficiency potential’ is critical for expediting the drug discovery process. The discovery of such tools that perturb cellular systems is of high value to the scientific community and may be facilitated by rapid forays into MCR space that can produce a multitude of novel scaffolds with appropriate decoration for evaluation with a variety of different screening paradigms.Novel hypervalent iodine mediated C-H activation methodologies is also an active area of interest. Probing the scope of the transformation below and investigating applications toward the synthesis of new peptidomimetics will be an additional pursuit in the Hulme group.

Publications

Novel applications of convertible isonitriles for the synthesis of mono and bicyclic γ-lactams via a UDC strategy

Hulme, C., Liang, M. a., Cherrier, M., Romano, J. J., Morton, G., Duquenne, C., Salvino, J., & Labaudiniere, R. (2000). Novel applications of convertible isonitriles for the synthesis of mono and bicyclic γ-lactams via a UDC strategy. Tetrahedron Letters, 41(12), 1883-1887.

Abstract:

This communication reveals a novel application of the so-called convertible isonitriles for the solution/solid phase generation of γ-lactam analogues. Use of tethered N-BOC aldehydes in the Ugi multi-component reaction (MCR), followed by BOC removal and base treatment (a '3-step, 1-pot procedure') affords γ-lactams in good yield. The UDC (Ugi/De-BOC/Cyclize) strategy, coupled with a convertible isonitrile, is now feasible from all three substitution sites of the Ugi product. A conceptually novel approach, combining a bi-functional precursor with a post-condensation modification to give fused lactam-ketopiperazines, is also revealed. (C) 2000 Elsevier Science Ltd.

Two step route to diverse N-functionalized peptidomimetic-like Isatins through an oxidation/intramolecular oxidative-amidation cascade of Ugi-azide and Ugi-3CR reaction products.

Hulme, C., Foley, C., & Shaw, A. (2016). Two step route to diverse N-functionalized peptidomimetic-like Isatins through an oxidation/intramolecular oxidative-amidation cascade of Ugi-azide and Ugi-3CR reaction products.. Organic Letters, 18, 4904-4907.

The solution phase synthesis of diketopiperazine libraries via the Ugi reaction: Novel application of Armstrong's convertible isonitrile.

Hulme, C., Morrissette, M. M., Volz, F. A., & Burns, C. J. (1998). The solution phase synthesis of diketopiperazine libraries via the Ugi reaction: Novel application of Armstrong's convertible isonitrile.. Tetrahedron Letters, 39(10), 1113-1116.

Abstract:

This communication describes the generation of high-yielding solution phase diketopiperazine libraries via a '3-step, 1-pot' procedure, employing the Ugi multi-component reaction (MCR), followed by BOC deprotection and cyclization to diketopiperazine (DKP). Exploitation of Armstrong's convertible isonitrile in the Ugi reaction utilising an 'internal nucleophile' approach for diketopiperazine formation is presented.

Molecular diversity: from small to large, emerging to enabling

Hulme, C., & Maggiora, G. M. (2008). Molecular diversity: from small to large, emerging to enabling. Current Opinion in Chemical Biology, 12(3), 257-259.

Synthesis of di- and tri-substituted imidazole-4-carboxylates via PBu3-mediated [3+2] cycloaddition

Hsu, M., Dietrich, J., Hulme, C., & Shaw, A. Y. (2013). Synthesis of di- and tri-substituted imidazole-4-carboxylates via PBu3-mediated [3+2] cycloaddition. Synthetic Communications, 43(11), 1538-1542.

Abstract:

Some new di- and trisubstituted imidazole-4-carboxylates were prepared from amidoacetic acids 3 in the present report. The key step to establish such imidazole- 4-carboxylates stemmed from the PBu3-mediated [3+2] cycloaddition between in situ-generated Δ2-oxazolinone 4 and ethyl cyanoformate6. Our results indicated that trisubstituted imidazoles 7-20 were afforded in better yields than those of disubstituted imidazoles 21-27. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications1 to view the free supplemental file. Copyright © Taylor & Francis Group, LLC.

Christopher Hulme