Helena Dennison (currently teaching Science in a secondry school in Bornmouth), Andy Bayly (currently post-docing with Chris Abell in Cambridge), Bingli (currently working in Los Angeles, USA), Vicky (just back from a post-doc with Samir Zard at Ecole Polytechnique, Paris) and Sarah Warren (currently post-docing with Thorsten Bach in TUM, Munich) were back to graduate with their PhDs in a ceremony in the Royal Albert Hall on Wed the 9th May:

S.A. Warren, S. Stokes, C.S. Frampton, A.J.P. White, A.C. Spivey, 'Synthesis of anti and syn Hydroxy-iso-Evoninic Acids', Org. Biomol. Chem. 2012, ASAP (PDF, 664KB).

The first synthesis of hydroxy-iso-evoninic acid, a pyridyl diacid found as a macrodilactone bridging ligand in bioactive Celastraceae sesquiterpenoid-based natural products, has been achieved in 9 steps and an overall yield of 26%. The synthesis utilizes a benzilic ester rearrangement (BER) and a late stage benzylic oxidation to give access to all four stereoisomers whose absolute stereochemistry was assigned following chromatographic separation and anomalous dispersion X-ray crystallography.

Evgeny Larionov, Mohan Mahesh, Alan C. Spivey, Yin Wei, Hendrik Zipse, 'Theoretical Prediction of Selectivity in Kinetic Resolution of Secondary Alcohols Catalyzed by Chiral DMAP Derivatives', J. Am. Chem. Soc. 2012, 134, ASAP (PDF, XMB).

The mechanism of esterification of the secondary alcohol 1-(1-naphthyl)ethanol by isobutyric anhydride catalyzed by 4-pyrrolidinopyridine (PPY) and a series of seven single enantiomer atropisomeric 4-dialkylaminopyridines has been studied computationally at the B3LYP/6-311+G(d,p)//B3LYP/6-31G(d) level. Comparison of the levels of enantioselectivity predicted computationally with the results obtained experimentally allowed the method to be validated. The value of the approach is demonstrated by the successful prediction that a structural modification of an aryl group within the catalyst from phenyl to 3,5-dimethylphenyl would lead to improved levels of selectivity in this type of Kinetic Resolution (KR) reaction, as was subsequently verified following synthesis and evaluation of this catalyst. Experimentally, the selectivity of this type of KR is found to exhibit a significant deuterium isotope effect  for 1-(1-naphthyl)ethanol vs. 1-duterio-1-(1-naphthyl)ethanol.

Tori Bob-Egbe completed her PhD viva on 2/03/12; external examiner Prof. Christian Bochet, University of Fribourg, Switzerland.

Daniel A. Offermann, John E. McKendrick, Jimmy J.P. Sejberg, Bingli Mo, Mary D. Holdom, Birgit A. Helm, Robin J. Leatherbarrow, Andrew J. Beavil, Brian J. Sutton, Alan C. Spivey, 'Synthesis and Incorporation into Cyclic Peptides of Tolan Amino Acids and their Hydrogenated Congeners: Construction of an Array of A-B-loop Mimetics of the Cε3 Domain of Human IgE', J. Org. Chem. 2012, 77, ASAP [PDF (2.39MB)].

The disruption of the human Immunolobulin E – high affinity receptor I (IgE-FceRI) protein-protein interaction (PPI) is a validated strategy for the development of anti-asthma therapeutics. Here, we describe the synthesis of an array of conformationally constrained cyclic peptides based on an epitope of the A-B loop within the Ce3 domain of IgE. The peptides contain various tolan (i.e. 1,2-biarylethyne) amino acids and their fully and partially hydrogenated congeners as conformational constraints. Modest antagonist activity (IC₅₀ ~660 mM) is displayed by the peptide containing a 2,2’-tolan which is the one predicted by molecular modeling to best mimic the conformation of the native A-B loop epitope in IgE.

Helena Dennison completed her PhD viva on 21/12/11; external examiner Dr Patrick Steel, University of Durham. She leaves the group to complete her Postgraduate Certificate of Education (PGCE, Bath University) and to become a Science teacher in Bournmouth, UK.