The MJH research group are based in the School of Chemistry, Newcastle University. We are a synthetic organic chemistry reseach group working in a number of areas of organic chemistry and chemical biology. This includes (1) the development of new synthetic methodogy, (2) the isolation and synthesis of novel small molecule antibiotics, (3) the synthesis of functional fluorophores for biological imaging and (4) the design of small molecule reagents for application in proteomics. The MJH group are based in the recently refurbished Johnson Laboratories in the Bedson Building, Newcastle University.
Natural Product Antibiotics from Actinomycetes
Actinomycetes are bacteria rich in bioactive natural products, many of which show antibiotic properties. Working in collaboration with a microbiology team we are interested in the isolation, structural solution and bioactivity investigation of new antibiotic natural products.
- Tyler A, Sejzi HM, Morton S, Waddell PG, Wills C, McFarlane W, Gray J, Goodfellow M, Errington J, Allenby N, Zenkin N, Hall MJ. Structural reassignment and absolute stereochemistry of madurastatin C1 (MBJ-0034) and the related “aziridine” siderophores: madurastatins A1, B1 and MBJ-0035. Journal of Natural Products 2017, 80(5), 1558–1562.
- Baksh A, Kepplinger B, Isah H, Probert MR, Clegg W, Wills C, Goodfellow M, Errington J, Allenby N, Hall MJ. Production of 17-O-demethyl-geldanamycin, a cytotoxic ansamycin polyketide, by Streptomyces hygroscopicus DEM20745. Natural Product Research 2017, 31(16), 1558–1562.
- Limited free e-prints available at http://www.tandfonline.com/eprint/TdAICE5cjEJ46Psbezw8/full
Chiral BODIPY Fluorophores
The synthesis and resolution of a class of chiral organic fluorophores, axially chiral 4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (Ax*-BODIPY), is described. Ax*-BODIPYs were prepared through a modular synthesis combined with a late stage Heck functionalisation. Resolution was achieved by preparative chiral HPLC. Absolute stereochemical assignment was performed by comparison of experimental ECD spectra with TD-DFT calculations.
- Clarke R, Ho KL, Alsimaree AA, Waddell PG, Bogaerts J, Herrebout W, Knight J, Pal R, Penfold T, Hall MJ. Circularly Polarised Luminescence from Helically Chiral ‘Confused’ N,N,O,C-Boron-Chelated Dipyrromethenes (BODIPYs). ChemPhotoChem 2017. In Press.
- Alnoman RB, Rihn S, OConnor DC, Black FA, Costello B, Waddell PG, Clegg W, Peacock RD, Herrebout W, Knight JG, Hall MJ. Circularly Polarized Luminescence from Helically Chiral N,N,O,O-Boron Chelated Dipyrromethenes.Chemistry - A European Journal 2016, 22(1), 93-96.
- Lerrick RI, Winstanley TPL, Haggerty K, Wills C, Clegg W, Harrington RW, Bultinck P, Herrebout W, Benniston AC, Hall MJ. Axially Chiral BODIPYs. Chemical Communications 2014, 50(36), 4714-4716.
Grignard Reagents as Reducing Agents
2,2,2-Trichloro-1-arylethanones undergo high yielding reductions to the corresponding 2,2-dichloro-1-arylethanones in the presence of RMgX. A single electron transfer mechanism for the reaction is proposed based on trapping experiments. Reaction of the intermediate enolates with a range of electrophiles is described, providing a convenient route to substituted α,α-dichloro-β-hydroxyketones and related molecules.
- Essa AH, Lerrick RI, Çiftçi E, Harrington RW, Waddell PG, Clegg W, Hall MJ. Grignard-mediated reduction of 2,2,2-trichloro-1-arylethanones. Organic & Biomolecular Chemistry 2015, 13(20), 5793-5803.
- Essa AH, Lerrick RI, Tuna F, Harrington RW, Clegg W, Hall MJ. Reduction of 2,2,2-trichloro-1-arylethanones by RMgX: mechanistic investigation and the synthesis of substituted α,α-dichloroketones. Chemical Communications 2013, 49(27), 2756-2758.
Recent Research Funding
2016: Studying the development of a new natural product antibiotic for the treatment of ESKAPE infections, Rosetrees Trust, £54,171
2014: A New Antibiotic for Gram Positive Bacterial Infections, Medical Research Council (MRC), £29,282
2013: A Novel Crosslinking Strategy for MS Structural Biology, Biotechnology and Biological Sciences Research Council (BBSRC), £116,056
2012: Probing the Mechanisms of dSTORM Reporters, Biotechnology and Biological Sciences Research Council (BBSRC), £118,521
2010: Towards commercial application of a novel method to prevent and remove bacterial biofilms, Natural Environment Research Council (NERC), £137,802
2010: Diels-Alder/Ene Reactions for the Multi-Component Synthesis, Engineering and Physical Sciences Research Council (EPSRC), £96,013