Our research effort is primarily focused on the total synthesis of natural products, exploring new strategies and concepts in chemical synthesis, and developing new synthetic methodology.
Total Synthesis: We have synthesized (and anticipated) a broad range of complex natural product structures, including alkaloids, terpenes, polyketides, shikimate-derived structures, and carbohydrate-derived structures. Through a relentless focus on step-economy, and by adopting a biomimetic philosophy, we aim to develop very short and efficient total syntheses. Our syntheses are characterised by new domino reaction sequences that rapidly and selectively generate molecular complexity (i.e., new bonds, rings and stereogenic elements). An area of particular interest has been examining how nature creates complexity through dimerisation processes, wherein relatively simple metabolites are converted into far more complex structures that contain no element of symmetry; a synthetic strategy which transcends all major biosynthetic pathways. In the Lawrence Group, we believe total synthesis research provides some of the best training in synthetic organic chemistry. Students encounter a wide variety of chemistry, use a number of experimental and analytical techniques, and need to constantly solve problems associated with reactivity and selectivity. Below you can see a selection of natural product targets we have successfully made (for further details see our publication list).
Methodology: We take strategic inspiration from biological processes to develop new synthetic methodology. For example, many domino reaction sequences can be found within biosynthetic pathways. A domino reaction involves two or more bond-forming reactions occurring under identical conditions, in which the latter transformations take place at the functionalities obtained in the previous reactions. Domino reactions are preeminent in contemporary synthetic organic chemistry as they have the ability to rapidly and selectively increase structural complexity. We are interested in developing novel domino reactions, such as the biomimetic domino oxa-Michael/Diels–Alder/oxa-Michael reaction sequence shown below, where we selectively generate 4 new bonds, 4 new rings and 8 new stereogenic centres in a single step. We also have an active interest in developing biocatalytic methodology, working in collaboration with colleagues in the Campopiano Group and our industry partners. For example, we recently reported a new bio-inspired amine donor NPP (N-phenylputrescine), inspired by the biosynthesis of the dipyrroloquinoline alkaloids, for use in transaminase mediated reactions. More generally, during our target-orientated research we often need to develop new synthetic methods ‘on-the-fly’. For example, we recently reported the first example of an enantioselective para-Claisen rearrangement, developed during our work on the illicium-derived prenylated phenylpropoanoids.
Enantioconvergent Reactions: An enantioconvergent reaction can convert a racemic starting material into a single highly enantioenriched product with a maximum yield of 100%. There are three established concepts for achieving enantioconvergency (see below). We are currently exploring a new concept within this field (unpublished), which we believe will have a transformative impact upon the entire field of asymmetric synthesis. This new approach will enable the use of racemic substrates which contain multiple and/or robust stereogenic elements in enantioconvergent reactions.