Total synthesis of natural products
We are working on the synthesis of a family of New Zealand marine natural products, the labillarides. These molecules were discovered by Peter Northcote’s group at Victoria University of Wellington and have unique structures. Their synthesis requires the development of new methodology, and will confirm the structures assigned to these natural products, allow their stereochemistry to be determined, and enable us to study their bioactivities more fully.
The fungal metabolite TAN-2483B may have potential as a treatment for cancer and osteoporosis. We have recently produced the central core of the structure.
The natural product pateamine has been shown to be an inhibitor of the initiation of protein biosynthesis (translation). We are working towards a synthesis of this compound and structural analogues in order to gain a greater understanding of the structure-activity relationships in this type of molecule.
Synthesis of natural product analogues
Following our total synthesis of the natural product aigialomycin D, we are preparing several new structural analogues for biological testing. The resorcylic acid lactones (RALs), of which aigialomycin D is a member, have a fascinating array of bioactivities, which we want to probe in order to design next-generation analogues with improved properties. Our compounds will be tested at the School of Biological Sciences to obtain new structure-activity relationships in the RALs family.
We are working towards the syntheses of several simplified analogues of the New Zealand natural product peloruside A, a microtubule targeting agent discovered by the Northcote group at Victoria University of Wellington. Our objective is to design an active analogue that can be easily synthesised with methods suitable for industrial scale-up. This would solve the current supply problems encountered with peloruside A and could enable a peloruside-type molecule to enter the market.
Synthesis of new designed compounds
We have discovered that sugar molecules with an attached cyclopropane ring partake in ring opening reactions to give various products depending on the reaction conditions. We are investigating the mechanism by which these processes occur and the scope of the resultant products.
The preparation of new carbohydrate mimics is important for medicinal purposes, as enzyme inhibitors and for incorporation into oligosaccharides. We are currently working on two approaches to the synthesis of these unnatural carbohydrates:
- derivatisation of C2-branched sugars (formed from cyclopropanated carbohydrates), by metal-catalysed coupling reactions
- formation of new C-glycosides (including C-disaccharides) by Wittig-type reactions and cyclisation.
Development of synthetic methodology
This work includes determining reaction mechanisms and finding new synthetic methods.
We are investigating an interesting side reaction in the well-known Horner-Wadsworth-Emmons reaction. The side reaction decreases the yield of the desired product but may be useful for producing alkene-phosphonates. We are currently fine-tuning the reaction conditions and learning how to control one pattern of reactivity over the other.
Available research projects
The following projects are available for postgraduate students:
- total synthesis of TAN-2483B
- synthesis of zampanolide analogues
- synthesis of peloruside A analogues