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Totally Synthetic by Paul H. Docherty, 6 August 2007

Total Synthesis of Geigerin


S. Carret, J.-P. Deprés, Angew. Chem. Int. Ed. 2007, 46, 6870-6873.

DOI: 10.1002/anie.200702031

Isolated from the plant colloquially known as the “vomiting bush”, Geigerin is a member of the guaianolide family, represented in the 5,7,5-tricyclic structure. No further mention of the biological activity is noted in this paper, but they do point out that this isn’t the first synthesis of this family, referencing Lee and Bartons works.

The synthesis starts with a bit of chemistry quite familiar to the group, doing a regioselective [2+2] cycloaddition with 2,2,2-trichloroacetyl chloride and 7-methylcycloheptatriene. In their previous papers, they had to use a metal to take diphosgene to dichloroketene, but in this case, a bit of ultrasound worked rather well. They then perform ring-expansion to give the 5,7-motif required.

A few steps further along, they used DMDO to generate the hydroxyl group with good substrate control, which formed the lactone under acid conditions. Not new chemistry, but a nice total synthesis!

The lactone product was then subjected to a rather tricky sp2-sp3 Suzuki coupling; the vinyl chloride starting material can’t be the best nucleophilic partner, and the methyl boronic acid is also a less than ideal partner. However, using rather standard conditions, they achieved the coupling with a reasonable yield.

I did like this approach to the target, and the use of some smart literature reactions.