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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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December 11, 2012

Natural Products Continue to Weird Me Out

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Posted by Derek

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.

Comments (16) + TrackBacks (0) | Category: Chemical News | Natural Products


1. JAB on December 11, 2012 12:23 PM writes...

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

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2. S. on December 11, 2012 12:46 PM writes...

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?

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3. Sili on December 11, 2012 12:46 PM writes...

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

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4. Foolery on December 11, 2012 1:04 PM writes...

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.

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5. Foolery on December 11, 2012 1:10 PM writes...

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

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6. pgwu on December 11, 2012 2:16 PM writes...

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.

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7. gippgig on December 11, 2012 2:49 PM writes...


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8. DWJ on December 11, 2012 2:50 PM writes...

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

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9. Sisyphus on December 11, 2012 3:02 PM writes...

The word "selective" has a whole spectrum of interpretations.

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10. mad dog on December 11, 2012 3:20 PM writes...

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.

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11. Morten G on December 11, 2012 3:50 PM writes...

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.

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12. Hap on December 11, 2012 4:01 PM writes...

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.

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13. Curt F. on December 11, 2012 10:20 PM writes...

@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?

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14. hn on December 12, 2012 3:16 PM writes...

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.

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15. TheEdge on December 13, 2012 9:06 PM writes...

@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.

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16. s2dsayer on June 21, 2013 10:18 PM writes...

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

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