Nichol, G. S., Gunawan, S., Zhigang, X. u., Dietrich, J., & Hulme, C. (2010). 2-Propyl 3,3-dibromo-2-hydroxypyrrolidine-1-carboxylate. Acta Crystallographica Section E: Structure Reports Online, 66(3), o597.
PMID: 21580358;PMCID: PMC2983708;Abstract:
The title compound, C8H13Br2NO 3, crystallizes as a non-merohedral twin with twin law -0.6 0 0.4/0 - 1 0 /1.6 0 0.6, and the structure has a refined twin domain ratio of 0.546 (5). The structure shows a compact conformation, with the ester unit roughly coplanar with a mean plane fitted through the non-H atoms of the pyrrolidine ring [dihedral angle = 8.23 (9)°]. In the crystal, inversion dimers linked by pairs of O - H⋯O hydrogen bonds generate an R 22(12) motif.
Hulme, C., Mathew, R., Moriarty, K., Miller, B., Ramanjulu, M., Cox, P., Souness, J., Page, K. M., Uhl, J., Travis, J., Labaudiniere, R., Huang, F., & Djuric, S. W. (1998). Orally active indole N-oxide PDE4 inhibitors. Bioorganic and Medicinal Chemistry Letters, 8(21), 3053-3058.
PMID: 9873675;Abstract:
This communication describes the synthesis and in vitro and in vivo evaluation of a novel potent series of phosphodiesterase type (IV) (PDE4) inhibitors. Several of the compounds presented possess low nanomolar IC50's for PDE4 inhibition and excellent in vivo activity for inhibition of TNF-α levels in LPS challenged mice (mouse endotoxemia model). Emesis studies (dog) and efficacy in a SCW arthritis model for the most potent PDE4 inhibitors are presented.
Hulme, C., Liang, M. a., Romano, J. J., Morton, G., Tang, S., Cherrier, M., Choi, S., Salvino, J., & Labaudiniere, R. (2000). Novel applications of carbon dioxide/MeOH for the synthesis of hydantoins and cyclic ureas via the Ugi reaction. Tetrahedron Letters, 41(12), 1889-1893.
Abstract:
This communication reveals novel applications of the CO2/MeOH reagent combination coupled with the UDC (Ugi/DeBOC/Cyclize) strategy. The Ugi five component condensation (5CC) affords carbamate protected amino-amides in good yield. When one of the supporting reagents employed in the Ugi reaction possesses a tethered amino-BOC protected functional group, subsequent acid treatment and proton scavenging results in rapid cyclization to cyclic ureas. Additionally, treatment of the 5CC product with base affords hydantoins in good yield, representing a novel and short approach to this class of molecule. (C) 2000 Elsevier Science Ltd.
Magnus, P., Roe, M. B., & Hulme, C. (1995). New trialkylsilyl enol ether chemistry: Direct 1,2-bis-azidonation of triisopropylsilyl enol ethers: An azido-radical addition process promoted by TEMPO. Journal of the Chemical Society, Chemical Communications, 263-265.
Abstract:
Treatment of triisopropylsilyl enol ethers with PhIO/TMSN3/TEMPO (cat.) -45°C results in 1,2-bis-azidonation, which appears to occur through a radical addition process; the 1-azido group can be replaced by carbon nucleophiles such as allyl, methyl, cyano, acetylene and acetonyl.
Baldwin, J. E., Hulme, C., Schofield, C. J., & Edwards, A. J. (1993). Synthesis of potential β-turn bicyclic dipeptide mimics. Journal of the Chemical Society - Series Chemical Communications, 935-936.