We have a keen interest in the function and use of enzymes as remarkable biocatalysts. Not only can their use in synthesis often allow reactions to be performed in a much more convenient way but their mechanisms and mode of action provide a wonderful insight into novel chemistries.

Much of our work focuses on the use of enzymes in the formation of sugars and their mimics. We are engaged in the isolation of some powerful new examples of the catalysts that nature uses to put sugars together.

This has led to the development of novel screening strategies that may be applied to all enzyme classes.[pub 59] Use of this powerful system has allowed us to dissect the mechanism and kinetics of glycosyltransferases.[pub 66][pub 67][pub 77][pub 83][pub 164 and the discovery of other synthetic carbohydrate biocatalysts.[pub 87][pub 143]

Some of these glycosyltransferases have been used, for example, to remodel antibiotics to create non-natural variants with higher efficacy.[pub 66]

Although the use of glycosyltransferases may in time allow the synthesis of all naturally occurring oligosaccharides, there is also a need for simple, easy-to-handle enzyme systems for the synthesis of oligosaccharides and non-natural glycoconjugates. We have identified novel catalysts and functions based on other enzyme types such as the glycosylhydrolases and tailored their use for synthesis.[pub 62][pub 87][pub 145]

We are interested in the use of engineered enzymes in which active-site residues have been specifically mutated or modified, and readily available enzymes, such as lipases and proteases (see Figure below). From this work, structural, kinetic and biochemical information links up to create a fascinating picture of the mechanisms of known and novel enzyme systems. Armed with this knowledge we can go on to exploit enzymes in a variety of ways from synthetic to medicinal.[pub 155][pub 163]

This work is conducted in collaboration with Prof. Gideon Davies.

Carbohydrates are powerful sources of chirality for use in synthetic asymmetric processes and often prove to be superior to more simple sources. Despite such clear indications, systematic structure-function relationships of carbohydrate ligands, reagents or catalysts are rare. This seems all the more remarkable given that they are a prime source of contiguous, stereogenic centres that may be readily manipulated both in configuration and functionality to allow rapid fine tuning of their function.

We explore the use of sugars to induce asymmetry, particularly in 1,2-additions to carbonyls,[pub 46][pub 56][pub 75] attaining promising stereoselectivities that outstrip those of existing systems. Systematic configurational alteration of scaffolds has allowed us to conduct some of the most detailed structure-activity relationship (SAR) studies to date. Recent work is developing carbohydrate organocatalysts.[pub 126]

Glucose is the most abundant organic moiety on the planet. Current estimates of oil supplies will allow only 20-30 years of our current petroleum-based synthetic strategies. Taught and adopted strategies have ironically moved away from chiral pool to simple oil-based building blocks, which while allowing conceptually elegant elaborations rely heavily on dwindling resource.

We explore new strategies (starting largely from sugars) and the re-birth of chiral pool/chiron methods that focus on biological origin, sustainable availability and true 'atom economy' (ie taking the energy that is supplied from the sun as the primary determinant of chemical strategy - "chemistry that grows on trees"). Ambitious chiron-type transposition taking advantage of existing selectivity bias (substrate control) allows minimal use of protecting group strategy during synthetic elaboration to key intermediates and target structures.