Molecules developed for use as drugs and materials are becoming increasingly complex. Our catalysis program is directed at developing new ways to rationally assemble core structures of such compounds. We are particularly interested in developing new process for assembly of decorated hetero- and carbocyclic structures from simple feedstocks. A central theme in our work is the pursuit of novel metallcyclic intermediates. Access to such structures from simple components can improve the efficiency of known reactions, but more importantly, provide inspiration for development new and diverted reaction pathways to molecular complexity.
For lead references see: Chem. Eur. J. 2013, pp7982; Chem. Eur. J. 2015, pp531; Dalton trans. 2015, pp5347; Chem. Eur. J. 2017, asap
Chemical and systems biology
Much progress has been made in cancer treatment using cytostatic drugs. A remaining challenge is suppression of recurrence and metastasis. We are working to develop a mechanistic understanding of how small molecule ionophores selectively targets stem-like cancer cells, a cell type that has been invoked as the culprit in failed treatments. In this respect the potassium selective ionophore salinomycin is of particular interest. We are pursuing both improved synthetic analogs of this structure and rationally designed derivatives aimed to develop a mechanistic understanding of the molecular basis for its activity.
For lead references see: Chem. Commun 2013, pp9944; ACS Med. Chem. Lett. 2016, pp635; BMC Cancer 2016, pp145; Chem. Eur. J. 2017, pp2077; ACS Central Sci. 2018 asap.
Complex molecule synthesis and semi-synthesis.
Several projects concerns target oriented synthesis of both carbo- and heterocyclic natural products. The structures are selected on the basis of a combination of biological activity and complexity of the molecular architectures. Both on a strategy level (planning) and in practice (bench work) we use target oriented synthesis to provide inspiration for advances in synthetic methodology.
In the context of total and semi-synthesis of natural products, we have a recently initiated program on new agents with activity against tuberculosis in collaboration with groups in Mexico, Uganda, and South Africa.
For lead references see: ACS Chem Biol 2014, pp1587.
Materials and odd molecules
Simple molecules can exhibit strange properties and be surprisingly difficult to synthesize. An example we have looked at is formyl silanes – a pyrophoric class of aldehydes. We also rely on crystallography in many of our projects. As part of this work we have in collaboration with Sven Lidins group described examples of allotwinning in molecular crystals. Allotwinning is an interesting phenomenon where a single structure can be solved from two (or more) intergrowing phases.
For lead references see: Acta Cryst B 2013, pp509; J. Org. Chem. 2013, pp12268.