Total Synthesis of Acetogenins and Lupin Alkaloids
Direct oxidative cyclisation of dienes using metal oxo reagents is one of the most elegant and concise approaches to the synthesis of tetrahydrofuran motifs present in an array of bioactive natural products. Structural and stereochemical complexity is introduced in a single reaction step, including up to four new stereogenic centres and a THF ring. Furthermore, absolute stereochemistry may be controlled through application of chiral auxiliaries, or by chiral phase catalysis in the permanganate-mediated variant of the reaction. This talk will provide an overview of the permanganate oxidative cyclisation reaction and illustrate applications in total synthesis.
The second part of the talk will look at an imino-aldol (or Mannich-type) approach towards lupin alkaloids. By controlling the relative stereochemistry (syn vs anti) in acyclic intermediates, sparteine or b-isosparteine stereoisomers can be synthesised. Recognition of a common quinolizidine motif, present in sparteine and matrine series (based on structurally isomeric skeletons) allows the approach to be applied in a structurally as well as stereodivergent fashion. The total syntheses of alkaloids in the matrine and sparteine will be described.