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Natural Products Continue to Weird Me Out

acetylene compound
Here’s a funny-looking compound for you – Ivorenolide A, isolated from mahogany tree bark, it has an 18-membered ring with conjugated acetylenes in it. That makes the 3-D structure quite weird; it’s nearly flat. And it has biological activity, too (immunosuppression, as measured by T-cell and B-cell proliferation assay in vitro). Got anything that looks like this in your compound libraries? Me neither.

16 comments on “Natural Products Continue to Weird Me Out”

  1. JAB says:

    After the enediyne antitumor antibiotics, nothing in the natural products world surprises me! Very cool…

  2. S. says:

    I read this paper yesterday. It has everything, isolation, elucidation of the structure, total synthesis of the compound, and biological results. My problem with it, is that the compound is not so potent, the synthesis has nothing special and is not considered biomimetic as they claim. Nothing really new derived from this paper, so why is it in JACS?

  3. Sili says:

    Finally something to do with those poly-yne compounds that don’t work as molecular wires.

  4. Foolery says:

    Who here thinks that %ee is bs? I know bromine has been used to enhance the ee of a CBS, historically; however, the alkyne has the Br pointed way far off into space if you draw the transition state out. I would argue that both side arms are of very similar steric bulk in the environment of the CBS catalyst.

  5. Foolery says:

    Also, the ee is just magically reported in the supplemental! No chromatogram no nothing! What kind of journal is JACS turning into these days?

  6. pgwu says:

    Wonder if they analyzed Chinese mohagany tree as well. I like to eat the tree leaves of toona and curious what makes it taste so good.

  7. gippgig says:

    Mycomycin

  8. DWJ says:

    sigh…
    another worthless natural product synthesis.
    We were doing the same 30 years ago

  9. Sisyphus says:

    The word “selective” has a whole spectrum of interpretations.

  10. mad dog says:

    The structure has some of the features of the lipoxins, which are anti-inflammatory agents derived from the leukotriene pathway. Sort of a lipoxin macrocycle with immunosupressive activity.

  11. Morten G says:

    mad dog is fairly right
    Thromboxane A2
    Hepoxilin A3
    Epoxyeicosatrienoic acid
    I assumed that the epoxide is required. Eicosanoid and non-eicosanoid signalling contains a completely unreasonable amount of molecules that look a bit like that one. But they aren’t cyclic. I guess this molecule could hit any number of enzymes and receptors in any mode.

  12. Hap says:

    1) “Biomimetic” seems like an overstatement – its probably an eicosanoid, so some of its biosynthesis might be known, but the key step doesn’t look like anything an organism might use. Conformational constraint doesn’t seem terribly biomimetic on its own.
    2) An epoxide and two propargyl alcohols seems like an invitation to acid-catalyzed addition/cyclization heaven. Guess it’ll be dosed IV?
    This synthesis just doesn’t seem really exciting to me.

  13. Curt F. says:

    @2: Nothing really new derived from this paper, so why is it in JACS?
    I think you do the paper — and the field of chemistry in general — a disservice.
    There isn’t a whole lot of true discovery science left in chemistry. It’s mostly all methods and applications. The chemistry of the natural world is one of those few places left where there’s a lot of natural discovery to do. What molecules are there on Earth? In general, we don’t know. This paper finds one more — and one with several novel structural and chemical features: a macrocycle with conjugated alkynes. Isn’t that a reason enough for the paper to be in JACS?

  14. hn says:

    Curt F., I agree with you. If it’s a cool new molecule, then it’s cool chemistry. Otherwise, we will paint ourselves into a corner. If chemistry is to reassert itself as the central science, then we chemists have to broaden our perspectives and reconnect with other fields.

  15. TheEdge says:

    @Foolery: There are a number of reasons to grumble about this paper, but the CBS reduction probably isn’t one of them. The difference between an alkyne and an olefin is significant enough to give good to excellent ee, even without the bromine. See the Evans Azaspiracid synthesis for one good example in TS (although that was a trans olefin).
    The authors here clearly should have given some proof of ee, though.

  16. s2dsayer says:

    I’d be willing to bet an endophyte’s responsible for the production of this thing…very interesting structure

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