Bioorganic Chemistry
Overview
Our group is interested in the synthesis of small molecules that can act as catalysts without the addition of metals – organocatalysts. Organocatalysis can be utilised for the construction of enantiopure complex organic molecules, thus providing an alternative or a complement to organometallic and enzymatic catalysts. It is interesting to note that a simple aminoacid, proline, is an excellent organocatalyst for several transformations, emphasising the “greener” properties of organocatalyts compared with traditional ones. We prepared a range of structural related organocatalysts, derived from tartaric and glyceric acids, with variation of the configuration of key functional groups and could draw interesting conclusions of the spacial and chemical features more determinant for the enantio- and diastereoselectivity outcome of the reactions studied. New organocatalysts are being synthesised and tested for several reactions.
Another area of interest is carbohydrate chemistry. One of our aims is to construct a library of carbohydrate derived hypersolutes using solid supported synthesis, which will provide us with a wide range of new compounds that will be tested by the Cell Physiology and NMR group for their ability to prevent protein aggregation and for protein thermostabilisation. In our studies, new glycosyl donors were used as well as a much simpler glycosylation method that has afforded the desired alpha anomeric selectivity and avoided the need of using expensive reagents. The synthesis of new solutes, with more chalenging structures, are being synthesised in solution and in solid phase, requiring better glycosylation selectivities. The synthesis of higher saccharides with important biological properties is another goal.
We are also collaborating with the Bacterial Signaling group in the synthesis of AI-2, a quorum sensing autoinducer, well known for its ability to mediate inter-species communication regulating important bacterial group behaviours such as biofilm formation, virulence, and antibiotic production. Because AI-2 regulates behaviors of human pathogens such as Vibrio cholerae, there is great interest in the discovery of non-natural quorum sensing modulators for applications in the treatment of bacterial infections. We developed a new synthetic approach for synthesizing the precursor of AI-2, 4,5-dihydroxy-2,3-pentanedione (DPD). The new strategy allowed the preparation of labelled DPD and new analogues. The labelled DPD constitute an important reagent for the ongoing elucidation of the biochemical fate of this molecule at the cellular level and the production of DPD. New DPD analogues are being synthesised, based on our highly reproducible DPD synthesis. These new compounds will be tested for agonist and antagonist quorum sensing properties. These results will open the way to novel methods to manipulate quorum sensing for controlling bacteria. A quantum dot (QD) will be linked to DPD to produce fluorescent labeled AI-2 (AI-2-QD), which will be a valuable tool to study several aspects of AI-2 signalling.
NOTE: AI-2 and related compounds are available for sale.
