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Totally Synthetic by Paul H. Docherty, 15 June 2006

Total Synthesis of Avrainvillamide and Stephacidin A & B


P. S. Baran, B. D. Hafensteiner, N. B. Ambhaikar, C. A. Guerrero, J. D. Gallagher, J. Am. Chem. Soc. 2006, 128, 8678-8693.

DOI: 10.1021/ja061660s

Detailing their syntheses of three related natural products in this article, Phil Baran’s group has been working rather hard on this funky dimeric natural product. Created via the spontaneous dimerisation of avrainvillamide, their total synthesis of this series is incredibly compact. To the business end:.

Thus, the synthesis plan now requires a construction of the monomeric unit, which begins with an impressive piece of new technology. Using palladium catalysis, they have developed a route to substituted tryptophans from simple precursors, inspired by some work published by Merck (DOI: 10.1021/jo970278i). After optimisation, they isolated the desired tryptophan in 75%.

Using this product, deprotection/protection led to the precursor for their benzopyran formation, which, itself, was created by propargylation of the free alcohol using an interesting literature procedure (DOI: 10.1016/S0040-4020(03)00862-7), involving generation of a vinylidene carbene generated in situ from propargylic carbonate, base, and catalytic CuCl.

All in, this is some pretty neat work. I urge you to read the paper (all sixteen pages!) - it’s top stuff!