Organic Chemistry
http://rsc.anu.edu.au/research/banwell.php
A major focus of activities is the development of new methods and strategies for the synthesis of biologically active natural products and their analogues. The use of cis- and trans-1,2-dihydrocatechols, (-)-3-dehydroshikimic acid [(-)-3-DHS], gem-dibromocyclopropanes, and pyrroles as readily available building blocks for that end represents a continuing theme. Aspects of this work are funded by Australian companies. For example, two APA(I)-funded PhD scholars have been working on research relevant to the activities of Melbourne-based Mimotopes Pty Ltd and Biota Holdings Ltd. Furthermore, Brisbane-based Progen Industries Ltd is funding two postdoctoral fellows who have been working on a collaborative project focused on novel carbohydrate chemistries. Two patent filings resulted from this last project in 2002.
Research highlights include the completion, in collaboration with colleagues at the University of Munich, of a total synthesis of the pharmacologically significant and structurally novel marine alkaloid halitulin. Poly-functionlised bis-piperidines related to the ecologically important haliclonacyclamine-class of marine alkaloid have also recently been obtained through a novel cross-coupling procedure whilst the stereo-controlled synthesis of enantiomerically pure sialic acids [from abundant (-)-3-DHS] has been achieved, as has a total synthesis of the cytotoxic styryllactone (+)-goniodiol. Various important methodological developments have occurred. These include the establishment of methods for converting (-)-3-DHS into derivatives of the (+)-enantiomer and the development of two distinct strategies for introducing the side-chains of the phomoidrides A and B onto a bicyclo[2.2.2]octanyl precursor to the carbobicyclic core of these biologically important and structurally complex natural products.
The electrocyclic ring-opening of ring-fused gem-dibromocyclopropanes continues to be exploited within the group as a key step in the construction of various natural products. A very concise method for construction of the polycyclic framework of the hapalindole class of alkaloids has recently been accomplished by such means.
Other work has focused on continuing the development of chemoenzymatic routes to the spinosyn class of insecticides. Indeed, a route to the carbotricyclic core of this compound has now been established but this will require improvement before it can be exploited in a total synthesis of the target insecticides. Utilising modifications of established cycloaddition methodologies, a concise route to the stilbenolignan aiphanol has been completed. Biological evaluation of this compound and various congeners has revealed that the compounds possess very potent and unusual biological properties. (with D.A.S. Beck, S. Chand, M.J. Coster, M.J. Harvey, B.D. Kelly, O.J. Kokas, P. Stanislawski, M.O. Sydnes, R. Taylor, D.J. Wong, and A.M. Bray [Mimotopes Pty Ltd, Melbourne], R.H. Don, V. Ferro [Progen Industries Ltd, Brisbane], C.C. Freeman, K.A. Jolliffe [U. Sydney], C.R. Parish [JCSMR, ANU], G.P. Savage [CSIRO Molecular Science, Melbourne], J.A. Smith [U. Tasmania])