Total synthesis of Merrilactone A and Anislactone A&B
Lei Shi
School of Chemistry, The University of Edinburgh, UK
Frontier Institute of Science and Technology (FIST), Xi’an Jiaotong University, China
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 report are our research efforts directed towards developing a conceptual 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.
References:
- Micheal Greaney*, Lei Shi, N. Nazef, Total synthesis of (±) Anislactone A and (±) Merrilactone A, Strategies and Tactics in Organic Synthesis, 2013, Vol 9, 105-147.
- Lei Shi, K. Meyer and M. F. Greaney*, Synthesis of (±) Merrilactone A and (±) Anislactone A. Angew. Chem. Int. Ed., 2010, 49, 9250-9253.
