Christopher Hulme

Christopher Hulme

Professor, Pharmacology and Toxicology
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-5322

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

Hulme, C., Liang, M. a., Kumar, N. V., Krolikowski, P. H., Allen, A. C., & Labaudiniere, R. (2000). Novel applications of resin bound α-amino acids for the synthesis of benzodiazepines (via Wang resin) and ketopiperazines (via hydroxymethyl resin). Tetrahedron Letters, 41(10), 1509-1514.

Abstract:

This communication reveals a novel application of resin bound α-amino acids coupled with the UDC (Ugi/DeBOC/cyclize) strategy. Reaction with either N-BOC-α-amino aldehydes or N-BOC anthranilic acids and subsequent acid treatment allows the preparation of highly pure and diverse arrays (approx. 10000 in size) of 1,4-benzodiazepines (Wang resin) and ketopiperazines (hydroxymethyl resin), respectively. Notable for the benzodiazepine series of compounds are the five potential points of diversity available from this two-step protocol. (C) 2000 Elsevier Science Ltd.

Ayaz, M., Xu, Z., & Hulme, C. (2014). Novel succinct routes to Quinoxalines and 2-Benzimidazolylquinoxalines via the Ugi reaction. Tetrahedron letters, 55(23), 3406-3409.

This communication reveals a unique, user-friendly, concise two-step, one-pot protocol for the synthesis of highly substituted quinoxalines. Conducting the Ugi reaction with appropriately functionalized classical Ugi reagents with subsequent acid treatment of the Ugi adduct affords collections of diversified quinoxalines in good to excellent yields. The methodology exploits what may be viewed as a 'convertible carboxylic acid', which in addition may be captured in an intramolecular sense to generate structurally complex 2-benzimidazolylquinoxalines in a mere two steps.

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