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Stephacidin A and Notoamide B   

27 February 2007 6,515 views 8 Comments

stephacidin-a.jpg

Williams, Tsukamoto, Greshock and Grubbs. ACIEE, 2007, EarlyView. DOI: 10.1002/anie.200604378.

As suggested in the comments on a previous article (thanks, “tired by chemistry”!), this synthesis of these related compounds 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 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 IMDA relatively quickly:

stephacidin-a_1.jpg
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.
stephacidin-a_2.jpg

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8 Comments

  • earth23 says:

    DOI not working

  • European Chemist says:

    A funny synthesis of some natural molecule just came out in JACS. DOI: 10.1021/ja0691728 Is it “Totally Synthetic” material? :-P

  • tired says:

    The Williams group has been working for a long time on this family of compounds (brevienamide, paraherquamide…). I think this is a very nice and short synthesis of Stephacidin A although it is not enantioselective.

  • WillisWill says:

    Or even that diastereoselective. I wonder if Jacobsen’s salen or someother catalyst would work…

  • Michael says:

    I found it very odd that they made a point to begin their synthesis with an enantioenriched starting material only to reach an achiral “flat” intermediate for their key IMDA step.

  • milkshake says:

    There are optically active oxazirines based on camphorsultam. (I think some are commercial.) For advanced intermediate like Streptacidine A the use of stoechiometric enantiopure reagent is non-issue. My guess is that they tried the homochiral oxazirin it on their racemic Streptacidin A and it did not work so great.

  • [...] a similarity to the stephacidin family, which has appeared in two previous posts here, one by Robert Williams, the other by Phil Baran.  However, there doesn’t appear to be a ‘family name’ – [...]