21 A new natural product assignment from the Fenical lab (JOC 2007, 72, 323-330) called piperazimycin. It shows potent anti-cancer activity against several cell lines. My guess is it has something with cation binding ’cause the pocket is pretty large. It could also be intercalative. It’s totally flippin sweet, what with that chloride in there. I can’t recall the guy’s name Indeed, I’m pretty Chris Walsh came here to give a lecture on the incorporation (the specific enzymes) involved in halogenation of organic molecules by sea slime. (thx commenters!) Some crazy shit out there.
Piperazimycin A
Here is a 2D version for you philistines.
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what a random halogen atom. i like it. plus thats a whole lot of oxygen atoms on the interior of that pocket…good old marine bacteria.
Wheres the post about ur pal Stoddart’s new ’switching memory’ chemistry published in nature yesterday? think of the amount of porn you could fit on there, plus it burns out after a short time so it cleans away the evidence after ur done with it. such possibilities.
Excellent work by Stoddart, glad to see you picked up on it.
I am insulted by your calling philistines.
I don’t know any philistines, so I didn’t call them. Must have been Kyle.
Oh, I didn’t see that “2D version for philistines” comment. I was too busy playing with the interactive 3D model.
I don’t get it.
From Wikipedia. http://en.wikipedia.org/wiki/Philistine
“In non-historical usage, the word philistine refers to a person deficient in the culture of the liberal arts or can also connote a smug and intolerant opponent of the bohemian who exhibits a restrictive moral code.”
i imagine its mode of action is not dissimilar to the lipopeptide antibiotic daptomycin, http://en.wikipedia.org/wiki/Daptomycin
Don’t know ’bout that. Daptomycin looks to me like its one of those amphiphillic structures that probably goes around disrupting cell membranes. The piperazimycin structure doesn’t give me the same impression.
The halogen is stuck right in the middle of nowhere. Bizzare structure. Most interesting to me is the origin of the piperazic acid moeities.
I wonder if the halogen is there to pick up interactions with oxygen lone pairs. Something I learned about last week is this whole notion of halogens interacting with lone pairs on oxygen to form what’s called a “halogen bond”, as opposed to hydrogen, I guess.
Bromine and iodine are better than chlorine for this, but for obvious stability reasons, chlorine pops up more often.
You mean ‘polarizability’, right? Bromine and Iodine are not that much more electronegative than carbon, but are much more polarizable. Well, chlorine is not going to form any kind of “bond” at all to oxygen that will matter.
Another small matter is that the chlorine is 100 meters away from any oxygens on the molecule, or the pocket where all the action probably occurs. It’s either for specific enzyme binding which results in its toxicity, and so a Me group can be used instead, or its a marker that was used in the biosynthetic pathway.
I doubt the activity would differ too much if a methyl group replaced the chlorine. Of course, I’m not a medicinal or natural products chemist, so I may be wrong.
If you look at the CPK spacefil, the chloride appears to have some interaction with that methyl heptane chain (what a fuckin’ odd amino acid), which may stabilize it in solution to some degree… though that’s possibly just an artifact of the solid state.
I also remember that enzymatic halogenation guy also gave a talk… but I can’t remember his name either. Hooray for sea slime!
I think the halogenation guy is Chris Walsh of MIT. Here’s a C&E News article about it:
http://pubs.acs.org/cen/covers.....ation.html
Walsh is at Harvard. He’s also a dick.
Really? What makes you say that? He seemed like a nice enough guy when I met him.
He’s certainly wasn’t shy about pointing out that Floyd Romesberg is full of shit. Then again, untempered honesty has its merits.
The structure in your 2D representation of piperazimycin is incorrect. The AMNA residue contains a conjugated diene. If you are interested there are some other very nice chlorinated molecules (cyanosporasides; Org. Lett. 2006,8, 1021-1024)that have recently been isolated by our group as well.
Ah. Quite right. I invite the reader to add the requisite degrees of unsaturation with a Sharpie.
Or read the article.
Verbose and insulting! A simple fuck off would have been enough.
That’s not what I was saying at all. I’m just saying… don’t hold your breath for a correction.