Some Natural Product Weirdness

Let's take a moment to take a look at the oddity of natural products. For an organic chemist, these things can sometimes be surprisingly bizarre, with structures that continue to provide the answer "Well, I would never have thought of it". I collect mostly oddnesses as I see them in the current literature, so let me unload some of them.

First of all, populosone, made by desert poplar (Populus euphratica) for its own reasons. You chemists will have seen many bicyclooctane frames over the years, but I bet you've never seen one with a ten-membered ring fused to it. Looking back, how many of us have ever seen a real ten-member ring merged or not merged with something else? It's a punch in the ring size area too difficult to form, and you really don't meet many of them. I've never done it in my life, at least not on purpose and therefore not like I've ever known (Modify: I originally watered its stereochemistry, but not its weird setting; it's now fixed).

Then there is Dragocin B, a natural marine product. The keen eyes will have already spotted this origin because of this malicious chlorine - marine organisms often introduce strange chlorine and bromine atoms into it, and it is a particularly strange place to put one. The rest of the structure is pretty funky as well - you usually don't get used to seeing furanoses (or any sugar with the anomeric center and the C-6 hydroxyl both attached back on the same partner to make a large ring (nine members in this case). It is interesting to note that this is closely related to an antibiotic compound isolated from a species of Streptomyces; some rather different organisms have had the same idea in general.

Drawing these things can be a little difficult, I must add. I found that the easiest way to get ChemDraw Dragomycin B was to start with the nine-membered ring, then remove a carbon and wedge it into furanose, and work from there.

Too many chiral centres, you say? Then look at Pusilatin B on the right. It looks more like a materials science experiment that went wrong than something that comes from a Japanese liver disease, but the plant makes a whole series of these animals by coupling two molecules from Riccardin C (which is also produced by a species of Siberian hares), simpler but still looking industrial. Liberal artists will recall that Ariel, in Shakespeare's The Storm, was considering taking a break from a cowhide flower; these compounds may have led her to rethink her thinking.

All right, one more. It is a slightly older compound, telomestatin. Would you have thought to make a ring from eight distinct azoles heterocycles? You wouldn't do it. And even if that were the case, you wouldn't have added those little grace notes of natural products like those two extra methyl groups or the thiazolidine that suddenly makes it all chiral.

It's another gift of the Streptomyces kind, always inventive, and it was discovered as a telomerase inhibitor, of all things. The drawing is surprisingly easy - you start with the horizontal link at the top, and when you put the next two five-member rings in, you rotate them to force the horizontal links. Then copy this unit, turn it over horizontally and draw the two vertical connections, align the two halves until they look straight. After that, it's just a matter of adding more heteroatoms and links; it's essentially an eight-element stop panel that has exploded. I tried to glue the SMILES chain of this Wikipedia article to save time, but as is often the case with funky structures, the look was so ugly that it hurt. You would have to attach a pork chop to it for a dog to play with this version, to adapt a sentence from my Arkansas education, so I made a little drawing.

That should be enough for a Monday. I have a lot more in my files, so I'll bring up some more alien weirdness another time. Have a good time!