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Totally Synthetic by Paul H. Docherty, 27 February 2007

Total Synthesis of Stephacidin A & Notoamide B


T. J. Greshock, A. W. Grubbs, S. Tsukamoto, R. M. Williams, Angew. Chem. Int. Ed. 2007, 46, 2262-2265.

DOI: 10.1002/anie.200604378

This synthesis by Robert Williams and his group is really quite nice. We’ve already had a look at this family, back in June of last year, with Phil Baran’s total synthesis of avrainvillamide and stephacidins A & B, and the relationship between the members of the family are reasonably well established, as is the biosynthesis. However, a recent report now brings the notoamides to this family, and Williams group were well set to complete the first syntheses (especially as Williams is a named author on the isolation paper, which was the neigbouring article in ACIEE!).

Their synthesis starts with a complex structure, apparently derived from tryptophan, which allowed them to build the flat precursor to their key intramolecular Diels-Alder reaction (IMDA) relatively quickly:

A sweet cyclisation, I think you’ll agree, completing the skeleton, and the synthesis after treatment with HCl. They then took their sample of stephacidin A, and were able to convert it to notoamide B, simply by treating it with an oxaziridine.