Let us take a moment to gaze upon the weirdness of natural products. For an organic chemist, these things can at times be startlingly weird, with structures that keep bringing on the “Well, I never would have thought of that” response. I collect especially odd ones as I see them in the current literature, so allow me to unload a few.
First off is populosone, made by the desert poplar (Populus euphratica) for reasons of its own. You chemists will have seen plenty of bicyclooctane frameworks over the years, but I’ll bet you’ve never seen one with a ten-membered ring fused to it. Come to think of it, how many of us have ever seen a real ten-membered ring fused to anything else or not? That’s smack in the too-hard-to-form ring size zone, and you really don’t come across them much. I’ve never made one in my life, at least not on purpose and thus not that I’ve ever known that I made. (Edit: I’d originally hosed up its stereochemistry, although not its weirdo framework; it’s now fixed).
Then you have Dragocin B, a marine natural product. The keen-eyed will have spotted that origin already because of that rogue chlorine – marine organisms often slap odd chlorines and bromines in, and that’s a particularly odd place to put one. The rest of the structure is rather funky as well – you’re generally not used to seeing furanoses (or any sugar with the anomeric center and the C-6 hydroxyl both tied back onto the same partner to make a large ring (nine-membered in this case). Interestingly, this is closely related to an antibiotic compound isolated from a Streptomyces species; some rather different organisms have hit on basically the same idea.
Drawing these things can be a bit of a challenge, I should add. I found the easiest way to ChemDraw Dragomycin B was to start with the nine-membered ring, then wipe out one carbon and wedge in the furanose, and work from there.
Too many chiral centers, you say? Then check out Pusilatin B at right. This looks more like a materials science experiment gone wrong than it looks like something that came from a Japanese liverwort, but the plant makes a whole series of these beasts by coupling two molecules of the simpler but still industrial-looking Riccardin C (which is also produced by a species of Siberian cowslip). Liberal arts types will recall that Ariel from Shakespeare’s The Tempest envisioned taking some break time in a cowslip flower; these compounds might have made her rethink.
All right, one more. This is a somewhat older compound, Telomestatin. Would you have thought to make a ring out of eight separate azoles heterocycles? You would not. And even if you did, you wouldn’t have tossed in those little natural-product grace notes like those two extra methyl groups, or the thiazolidine that suddenly turns the whole thing chiral.
This is another gift from the ever-inventive Streptomyces genus, and it was discovered as a telomerase inhibitor, of all things. Drawing it is surprisingly easy – you start off with the horizontal bond at the top, and when you put the next two five-membered rings in you rotate them to force horizontal bonds. Then copy that unit, flip it horizontal, and draw the two vertical bonds, aligned the two halves until they look right. After that, it’s just slapping in heteroatoms and extra bonds; it’s basically a blown-up eight-membered stop sign. I tried pasting in the SMILES string from that Wikipedia article in an attempt to save time, but as often happens with funky structures, it came out looking so ugly that it was painful. You’d have to tie a pork chop to it to get a dog to play with that version, to adapt a phrase from my Arkansas upbringing, so I did a quick redraw.
That should be enough head-scratching for a Monday. I have plenty more of such things in my files, so I’ll bring out more alien oddities another time. Enjoy!