It’s Clickalicious and Web-Two-Zeroey!
December 2nd, 2009 by LiqCAs bioorthogonal as CBC is, we still have some respect to biofolk.[1] See, these people won’t be anywhere without chemistry. The sun of Barry Sharpless shines real close to me and burns me with the hot fire of click chemistry.[2] While the initial message was directed at medchem people as a new way to think about creating diversity, the reliable reactions that work on any scale is something that everyone likes. Even biologists, with their inability to step outside of the Eppendorfs full of hella dilute and sensitive stuff. Especially biologists. This is why our lab looked into what makes The Click Reacion fail on biological substrates, and how to prevent it in ways other than making unhappy compounds resembling the crazy scribble of the neophytes who don’t know any better. Bertozzi’s cyclooctynes are incredibly cool in their own right, their only problem is relatively low reaction rates and lengthy synthesis. The ability to adapt the original click conditions to mid-micromolar concentrations of vulnerable macromolecules is, in my view, quite impressive. You’d better agree.
Now, you’ll be surprised how easy it is to screw up this great reaction. I couldn’t get it work in a chemical setting myself from the first time. So, we’ll be holding an online help session on clicking things. If you ever had any difficulties with copper-catalyzed azide–alkyne cycloaddition in any setting, please report here. You can write us an e-mail, but for obvious reasons (blogging powers!) I prefer it to be discussed here. It will help us address the problems that other people are facing, and, hopefully, solve some of them right away.
[1] Right?..
[2] Try mixing neat phenylacetylene and benzyl azide with copper (I) source if you don’t believe me.
“we still have some respect to biofolk.” lol no.
A trace of respect. Mostly for people who do biomaterials
Click? Click this – a novel about organic chemistry graduate school, ghosts, revenge, and high explosives.
http://www.amazon.com/Novel-Efficient-Synthesis-Cadaverine/dp/1448627176
I have clicked this a long time ago. Just so you know, the more suggestions of doing this I see, the less likely I am to read it. But it does sound interesting.
Has anybody created a liquid carbon? I have a low pressure, highly explosive gas with twice the power of gasoline, that produces zero parts per million hydrocarbons, seen on a readout from a smog analyzer. I also have a non flammable, oily liquid that has a boiling point above 500 degrees Fahrenheit, which I think might be liquid carbon, because both the liquid and gas are made from gasoline. Go to You Tube, White Gasoline Vapor, read everything, including comments. Help me find a chemistry lab, not connected to oil, to have the gas analyzed.
Please do us a favor, report your findings in a proper manner.
Wow. This is like Uncle Al without the high IQ. Is this what the rest of the internet has to put up with?
Take more vicious shots at the biologists next time. Coffee-sipping slackers, don’t make their lives easier, especially not with cool chemistry.
There’s just one problem with this: it is them who are the end users… chemists aren’t terribly excited about making triazoles.
I love triazoles, well actually I don’t but the name makes me laugh. I seriously wish I wasn’t so damn jealous of the biologists and their coffee.
Wait, chemists aren’t supposed to drink coffee? Huh?
Of course we’re supposed to drink coffee. Coffee is a gift from the caffeine gods. They become angry if we reject their blessings.
I have searched long and deep and never really found a good reason to make a triazole…
lets not hammer click chemistry – 4,5-dinitrotetrazole does not like to be dissed
triazole, sorry
Now you’re talking about O. Christe chemistry! Kapow!
So are there any examples of well-known medicinal compounds that have triazoles? (I don’t really know of any, but that doesn’t mean much.)
Lots of anti-fungals… but they are mostly 1,2,4 triazoles, not the “click” 1,2,3’s.
Tazobactam – a beta-lactamase inhibitor used with the penicillin drug Piperacillin contains a 1,2,3-triazole.
Rufinamide – a recently approved anti-seizure drug contains a 1,2,3-triazole
Part of the problem with 1,2,3-triazoles as medicinal compounds is the scale-up required by the pharmaceutical industry. Large amounts of organoazides and copper-azides are a concern for explosions when you need them beyond kilogram scale.
Oh, come on. I thought we’re through this.
Here: azides on ton scale.
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Fixed. It’s a paper from Roche about improved synthesis of Tamiflu from shikimic acid.
Try mixing neat phenylacetylene and benzyl azide with copper (I) source if you don’t believe me Were there any C-C single bonds among the 15 carbons in the pot? Oh yeah, two. What did your one-eyed granny say about dry copper acetylides? Copper azides?
Micromolar aqueous is a silly thing only found in alien milieux. Micellize! TEMPO – because a stable free radical is always publishable re “Hardon” McConnell at Stanford. Oh, wait… 21st century. Make that a stable carbene ligand on Cu(I) to control solubility and clustering, then triazole HIV inhibitors. Do it membrane-anchored – always a rock-solid excuse for
failuremore studies needed. “Who cares if it works? We have three years of grant funding!”http://en.wikipedia.org/wiki/1,3-dipole
So maybe.. nitrile oxides? (with a pulsed EM field!)
The concentrated click blows up because of the energy within a triple bond and three nitrogens is released in one fell swoop. Higher copper (and silver) acetylides are quite benign.
It’s all been done.
Process scale-up: maybe one could do a concentrated click on water, with some lazy copper source like Cu2O and sonication. Water soaks up lots of heat. I think the more unpleasant part is working with large quantities of some low-MW azide, but many times these can be easily generated and handled as solutions.
I am contemplating myself working with methyl azide soon, for Aube-Schmidt reaction. (I will report on the size of the resulting hole)
I can’t wait know why do you have to use such a perverted method to make methyl amide.
Well, take care. It’s not too bad. I’ve seen people who handled grams of pentaerythtryl tetraazide. Symmetry makes a good stabilizer. Triazidopentaerythritol is sitting in our freezer as a solution in 1 L of ether with unknown concentration, that scares me more.
I think you mistook my post comment about coffee earlier. I have no problems with Chemists drinking coffee. I have a problem with biologists that every time I see them it is with a coffee in hand or in a cafe drinking coffee. It was more of a reference to how much spare time they have than a slander on the coffee drinkers of the world. Similarly Engie’s are too often in the pub, I love beer but don’t have as much time as time to drink it.
well, you know. Engineers are all about efficiency. Less time in the lab = more time in the bar. Work smarter, not harder. Most organic chemists do not have this mentality.