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Palau’amine   

23 February 2007 13,483 views 18 Comments

palauamine.jpg

Köck and Grube.  ACIEE, 2007, EarlyView. DOI: 10.1002/anie.200604076.

An interesting debate has sprung up in the comments on this little beastie (thanks for the tip, folks!), as several groups around the world are working on palau’amine as a target. However, this Angewantde reports the isolation of a family member, tetrabromostyloguanidine, with different relative stereochemistry. Most interestingly, the deviation appears to be centred on the ring junction on the fused saturated 5,5 rings – with a trans ring junction in the newly isolated product. The NMR evidence in itself is convincing, and the molecular modeling adds to that opinion, so perhaps it’s time for a rethink?

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18 Comments

  • Hap says:

    Is your top right ring accurate? That looks like a 3H-pyrrole; if that is the correct tautomer, there should be a stereocenter at the uppermost 6.5 junction (or it should be the 1H-pyrrole tautomer with no stereocenters at the uppermost 6.5 junction.)

  • ranfiddler says:

    It’s time to rethink the structure, I totally agree… any core-structure model study will be helpful to tell the relative stereochemistry at C12 and C17.

  • ... says:

    Given that Baran is acknowledged on this Angew. paper, does anyone know if we should expect to see a synthesis soon or is this paper perhaps what spawned the earlier rumors?

    Also, Paul, there are two other papers that deal with this topic noted in the Papulacandin D comments. Perhaps you could add DOI’s for them to this post.

  • Jimbo says:

    How many grad student years has Palau’amine wasted?

    Someone (prolly Baran) needs to make it already and end everyone else’s misery.

  • anon says:

    If this new structure is correct, and the axinallamine core and palau’amine core are one and the same, Carreira is not far off and Romo is not too far behind him.

  • anon says:

    Natural Products, Stylissadines A and B, Specific Antagonists of the P2X7 Receptor, an Important Inflammatory Target1
    Malcolm S. Buchanan, Anthony R. Carroll, Rama Addepalli, Vicky M. Avery, John N. A. Hooper, and Ronald J. Quinn
    Web Release Date: 22-Feb-2007; (Article) DOI: 10.1021/jo062007q

    This article revises the structure of 4,5-dibromopalau’amine as well.

  • anon says:

    and another one

    Carteramine A, an inhibitor of neutrophil chemotaxis, from the marine sponge Stylissa carteri
    Pages 2127-2129
    Hirotsugu Kobayashi, Koki Kitamura, Koji Nagai, Yoichi Nakao, Nobuhiro Fusetani, Rob W.M. van Soest and Shigeki Matsunaga

  • anon says:

    sorry – thought I had copied the journal:

    Tetrahedron Letters 48 (2007) 2127–2129

  • anan......... says:

    with Reference to comment one

    Top right ring has no stereocenter. It is 1H-pyrrole. The styloguanidines and plauamines differ in therir connections at this ring juncture. Palau’amine has C-N pyrrole connection where as Styloguanidine has C_C pyrrole connection.

    It is still puzzling to accept that the ring (5,5) fusion is trans as opposed to the Kinnel’s cis proposed strcture.

    Can any body get Prof. Baran to comment on this, based on his total synthesis of Palau’amine and there by save the time of other groups in solving the structural assignments. Instead they can switch their strategies. That would help with tight budgets.

    These turned out to be versatile molecules to go after.

    anan………

  • TWYI says:

    Could this be diazonamide all over again..

  • compchem says:

    It appears also the stereocentre of C20 (hydroxyl) of palau’amine has been revised in this paper but the authors don’t mention this – have I missed something? The isolation paper of palau’amine (JOC 1998, 63, 3281) has C20 as (S) but in this paper it is (R)…
    Cheers…

  • Beth Halford says:

    It’s relative stereochemistry, not absolute stereochemistry. Also, I think that alcohol’s configuration was originally assigned correctly (JACS 1993, 115, 3376), then reassigned, then rereassigned. It’s confusing. I could be wrong.

  • anonym says:

    yea, obviously there was something wrong with the structure…Otherwise how do you explain that Overman published a JACS paper of palau’amine fragment in 1997 and since that time there was no follow up from that group….Usually it means something.

    Also I worked with palau’amine myself, trying to identify its mechanism of action. In the original paper it is said that palau’amine is a potent immunosuppressant (inhibits T-cell proliferation) IC50 5-10 nM. I never was able to reproduce those IC50, although we collaborated with the immunology lab. My IC50 (natural sample) were about 5-10 uM, and I did not know what the deal was. So I abandoned the project and successfully graduated anyway….May be I did something wrong, or there was something wrong with my natural sample, but…those are kinda results I got..

  • skelly b says:

    Is T-Cell inhibition the same as a “mixed lymphocyte assay”. I was always bothered by the lack of experimental description of the immunosupression assay in the original palau’amine isolation paper.

  • axicon says:

    FYI: the Baran article just dropped in Nature

    http://www.nature.com/nature/journal/v446/n7134/pdf/nature05569.pdf

  • Tot. Syn. says:

    Yep, just finished reading it. Post on it soon…

  • [...] One quick inspection, and you know we’re looking at a dinoflagellate neurotoxin, with more guanidine groups and derivatives than you can shake a stick at.  Unlike other large families of natural products with common functionalities, there doesn’t seem to be a universal strategy that (whilst ugly) could synthesise the majority of the family.  This means we get to see a whole variety of strategies towards these targets (and ultimately, the daddy, palau’amine). [...]