Greaney, Mike

Lusby, Paul

Shi, Lei

Engineering and Physical Sciences Research Council (EPSRC)

ORS

2011-11-25T15:41:18Z

2011-11-25T15:41:18Z

2011-11-23

Merrilactone A (1) was isolated in only 0.004% yield from the methanol extracts of the pericarps of Illicium merrillianum. Structural elucidation of Merrilactone A revealed a compact, cage-like pentacyclic architecture of high molecular complexity, featuring seven stereocentres, five of which as contiguous fully substituted carbon atoms, two γ-lactones and a central oxetane ring. Merrilactone A also exhibits an important neurotrophic activity, significantly promoting neurite outgrowth in the primary cultures of foetal rat cortical neurons at very low concentrations. Structurally, merrilactone A is related to anislactones A and B, a pair of epimeric sesquiterpene dilactones discovered ten years earlier by Kouno and co-workers from the related Illicium anisatum plant. Fukuyama has shown that anislactone B can be converted into merrilactone A using a simple three step sequence, suggesting that the anislactones may be biogenetic precursors to merrilactone A. Described in this thesis are our research efforts directed towards developing a conceptually novel synthetic route enabling regiodivergent total synthesis of both anislactone A / B and merrilactone A. Our synthetic route (around 22 steps) features several key reactions, which include a [2+2] photo-cycloaddition reaction, Tiffeneau-Demjanov ring expansion and titanium(III) mediated radical cyclization.

http://hdl.handle.net/1842/5705

en

The University of Edinburgh

natural products

total synthesis

Merrilactone

neurite outgrowth

Total synthesis of (±)-Merrilactone A and (±)-Anislactone A

Thesis or Dissertation

Doctoral

PhD Doctor of Philosophy