Medda, F., & Hulme, C. (2014). Exploiting the Divalent Nature of Isonitriles: a novel Pictet-Spengler Amidination process. Tetrahedron letters, 55(22), 3328-3331.
An isocyanide-based multicomponent reaction (IMCR) utilized for the rapid assembly of novel, biologically relevant dihydropyrrolo[1,2-a]quinoxalines-amidines is herein presented. Starting from 1-(2-aminophenyl)pyrroles, aldehydes, and isonitriles, the target heterocyclic scaffold is assembled in a one-pot, operationally friendly process. With three points of diversity and formation of three chemical bonds in one step, this strategy proves to be very general. Novel, mild methodology for the generation of amidines from secondary amine anilines and isonitriles is also introduced.
Lynch, V. M., Hulme, C., Magnus, P., & Davis, B. E. (1995). Novel 2- and 5-azido-N-(diphenylcarbamoyl)proline methyl esters. Examples of a novel proline oxidation.. Acta crystallographica. Section C, Crystal structure communications, 51, Pt 12/-.
PMID: 8588859;Abstract:
The crystal structures of two azido-substituted proline derivatives are reported. Racemic 2-azido-1-(diphenyl-carbamoyl)proline methyl ester, (I), C19H19N5O3, is resolved upon crystallization from methylene chloride-diethyl ether. The azido moieties are nonlinear with N--N--N angles of 173 (1) and 170.3 (2) degrees for (I) and (II) [cis-5-azido-N-(diphenylcarbamoyl)proline methyl ester, C19H19N5O3], respectively. Close intramolecular contacts between the carbonyl O atom of the amide and the central N atom of the azido group are found. The contact distances between N7 and O14 are 2.780 (14) and 2.815 (2) A for (I) and (II), respectively.
Lin, C., Lu, P., Yang, C., Hulme, C., & Shaw, A. Y. (2013). Structure-activity relationship study of growth inhibitory 2-styrylchromones against carcinoma cells. Medicinal Chemistry Research, 22(5), 2385-2394.
Abstract:
The structure-activity relationship study of 2-styrylchromones against carcinoma cell growth is discussed in the present report. Taking advantage of 2-styrylchromone as a molecular template, a series of structural modifications was carried out and examined on several carcinoma cell lines. Interestingly, AGS cells exhibited more sensitivity in response to methoxy-bearing compounds, of which compound 23 (3,4,5-trimethoxy group on ring B) showed the most potent activity with a GI50 value of 1.3 μM. Surprisingly, as methoxy groups in 12 and 24-27 were demethylated to generate their hydroxyl counterparts 28-32, none of them displayed appreciable activity against all carcinoma cells. We further confirmed the pivotal role of rigidity for growth inhibitory activity between the rigid 12 and its flexible counterpart 33. Taken together, in the present report, we have clearly demonstrated the structure-activity relationship study of 2-styrylchromones targeting carcinoma cell growth. © 2012 Springer Science+Business Media, LLC.
Hulme, C., Shaw, A. Y., Xu, Z., & Hulme, C. -. (2012). Ugi/Robinson-Gabriel reactions directed toward the synthesis of 2,4,5-trisubstituted oxazoles. Tetrahedron letters, 53(15).
This Letter discloses a novel concise synthesis of a series of 2,4,5-trisubstituted oxazoles via a tandem Ugi/Robinson-Gabriel sequence. Herein, 2,4-dimethoxybenzylamine 1 was used as an ammonia equivalent in combination with arylglyoxal 3 and supporting Ugi reagents, an isonitrile and carboxylic acid. As such the product of the acid treated Ugi intermediate is ideally configured to undergo a Robinson-Gabriel cyclodehydration reaction to yield the desired oxazole scaffold 5.
Hulme, C., Peng, J., Tang, S., Burns, C. J., Morize, I., & Labaudiniere, R. (1998). Improved procedure for the solution phase preparation of 1,4- benzodiazepine-2,5-dione libraries via Armstrong's convertible isonitrile and the Ugi reaction. Journal of Organic Chemistry, 63(22), 8021-8023.
