Professor D.R. Boyd
BSc (Queen's University of Belfast), 1963
PhD (Queen's University of Belfast), 1966
DSc (Queen's University of Belfast), 1977
Emeritus Professor of Organic Chemistry
Tel: + 44 (0) 28 9097 4421
Fax: + 44 (0) 28 9097 6524
The growing degree of overlap between chemistry and biology has been facilitated by recent advances in instrumental techniques which now allow biology to be studied at the molecular level. This is reflected in the search for new routes to enantiopure molecules involving the use of both enzymatic and non-enzymatic methods which has been driven by the pharmaceutical and agrochemical industries where the structures of active sites and receptor sites have been established and where biological responses often differ according to chirality. Enzymes behave as natural robots which can assemble or breakdown molecules using an assembly-line approach. The use of intact cells (bacterial and fungal) as wild type, inducible and constitutive mutant, or recombinant strains and pure enzymes are currently being used to obtain a wide range of non-racemic chiral bioproducts. This work forms part of a multidisciplinary network involving research chemists (postdoctoral fellows, postgraduate students, and technicians), molecular biologists and microbiologists based in Belfast, and collaborating laboratories in England, Ireland, Poland and the United States.
The mechanism, stereochemistry and sequence of enzyme-catalysed reactions are being studied in order to understand the fate of anthropogenic molecules in the environment, to detect new types of metabolic intermediates, and to understand the origin of chemically induced carcinogenesis at the molecular level. Utilisation of the state-of-the-art chromatographic,spectral and biotransformation facilities within the School, has allowed the detection and isolation of many bioproducts which were previously unknown or only postulated as transient intermediates. Some examples of the new metabolite types derived from small molecule substrates currently under study are shown below:
The majority of enzymes currently in use are of the redox type (dioxygenases, monooxygenases, dehydrogenases and reductases). Using these enzymes both asymmetric synthesis and kinetic resolution methods are being applied in the quest for single enantiomer products from xenobiotic substrates. Alkane, alkene and arene mono- and poly-hydroxylation, epoxidation, heteroatom oxygenation, dealkylation, dehydrogenation, and deoxygenation reactions are among the enzyme-catalysed reactions currently under study. These enzymatic methods have provided a wide range of new single enantiomer products as starting materials for chiral reagents, chiral ligands and chiral target molecules, e.g. carbasugars and alkaloids, which are not readily available by other routes.
The availability of different types of enzyme and enantiodivergent synthetic procedures now allow us to isolate an increasing number of bioproducts as single enantiomers of opposite configuration. The use of new recombinant strains in combination with techniques such as site directed mutagenesis are under study and hold out the promise of being able to improve stereoselectivity and yield, and may indeed allow enzymes to catalyse types of reaction not previously found in nature.
Single enantiomer compounds (e.g. monols, diols, triols, tetrols, ketols, sulfoxides, and derived epoxides, aminoalcohols) now readily obtainable in gram quantities from the biotransformation methods, are currently being investigated for their applicability in synthesis. Thus new chiral reagents for non-enzymatic asymmetric synthesis (oxidation, reduction), the kinetic resolution and enantiopurity determination and new synthetic routes to natural (e.g. alkaloids, marine metabolites) and unnatural (e.g. carbasugars). The potential of larger bioproducts and of smaller polyfunctionalised bioproducts obtained using enzymes having larger active sites and of tandem biotransformations in the synthesis of molecules having a particular type of biological response is currently under study. While to date the enzyme-catalysed work has largely involved the use of available substrates, the next phase will involve a higher proportion of chemical synthesis steps in the production of substrates and chemoenzymatic route to target molecules of interest to the pharmaceutical and agrochemical industry.