Have you ever noticed that, once a given idea gains acceptance in the community, everyone starts seeing its exemplification practically everywhere? I am not saying this is without merit, but I am sure you might agree that there was a time when no one looked at water as an “extra” in DFT calculations. Then water turned into an integral part of virtually every mechanism. Another example is when everyone started showing concerted metalation/deprotonation in C-H activation mechanisms. The list goes on and on. One particular modern trend that I notice is towards involving single electron transfer i ..read more

In the 19thcentury chemistry papers people routinely described how they had eaten or smelled the compounds they were making in the lab. By today’s standards, this practice is foolish, although there are enthusiasts who still resort to this dubious methodology. But let’s dig a little deeper. While tasting the products of one’s synthesis is reckless, let’s remember the teachings of Helmholtz. Among many of his original research contributions is an argument about the role of visual sensation in science (http://study.sagepub.com/sites/default/files/Hermann%20von%20Helmholtz.pdf). All of our scient ..read more

From time to time I will write short essays on artificial intelligence (AI). AI is something that I know little about, so please forgive my ignorance. Wait… What I just said already sounds dangerously foolish because, if I am not an expert, I should probably pipe down. But I won’t be quiet because AI is now everywhere and, at its core, it commonly employs linear regression analysis, which has been around forever. At least this is what I would like to believe at this stage. I am starting to read Bostrom’s “Superintelligence” and it paints a rather gloomy picture that is in store for us if thing ..read more

As you may recall from basic biochemistry courses, introns represent long stretches of noncoding DNA between exons. The latter are the bread and butter of genetic processes because they carry the code that makes us who we are. Introns (junk DNA) may have a functional role in biology, but no one has been able to show it in any rigorous manner. Now there are definitive accounts that suggest that junk DNA has a meaning. In yeast, introns persist after splicing and appear to be associated with cell growth regulation under stress. You can read about this fascinating find in the link below, but I ca ..read more

I have to get back to blogging, partly because I miss it and partly because RSC mentioned that I had a blog when they ran an announcement related to my new position as an Associate Editor of Chemical Science (http://blogs.rsc.org/sc/2018/12/20/meetandreiyudinchemicalscienceassociateeditor/?doing_wp_cron=1547228932.9969739913940429687500). Some people are wondering what has been going on, why I am not posting anything. So I guess this is as good a time as ever to get back to writing. Fittingly, we had Prof. Kei Murakami of Nagoya University visit us yesterday as part of his Canadian tour ..read more

In part due to my long-standing interest in heterocycle-driven drug discovery, I was kind of surprised to see this Org. Lett. paper. In this article, Boger and colleagues showcase a fascinating new way of making vinylogous formamides from 1,2,3-triazines. What is curious here is the very fact that triazines can participate in nucleophilic addition reactions. I have seen many attempts to introduce these rings into bioactive substances, but now that triazines have been shown to be excellent electrophiles toward amines, I should adjust my expectations for this class of molecules. In the Boge ..read more

I was visiting Novartis in Basel, Switzerland, over the past 3 days. It is an amazing site, with astounding architecture. They even have a Frank Gehry building, a dinosaur skeleton, and a Japanese restaurant on campus. I went out for dinner with Dr. Fabrice Gallou last night and learned about the “business of cyclosporine A” at Novartis. The graphic below showcases the degree of sophistication achievable with complex molecules. The overall goal of the methylation reaction is to site-selectively cleave cyclosporine, run Edman degradation in order to remove the N-terminal amino acid, couple ..read more

My lab and I have been heavily entrenched in the design of boron-containing covalent inhibitors of proteases. In my view, synthetic students optimally relate to the challenges of chemical biology when they think about the fundamentals of polar bimolecular reactivity. This is exactly what I like to teach in my classes when I describe enzymes as giant nucleophiles. If you then take a look at the electrophilic options out there, you might first consider epoxides, aziridines, and acrylates. These molecules are useful, but are somewhat boring because they offer a singular outcome upon interaction w ..read more

I typically do not comment on deprotection conditions, but there is something special in the two papers below. When I read the one by Lattanzi and colleagues, I thought that their nice asymmetric chemistry had been somewhat overshadowed by a single carbamate cleavage condition using TBAF. I am not sure how many of you are experienced with aziridines, but they do not easily withstand typical Boc removal with TFA. When I saw the yield of 98%, I was literally floored. In the interest of full disclosure, I learned about this deprotection from a paper I recently refereed. I dug a bit deeper and fou ..read more

I am a fan of small amine-containing compounds with relatively short history in synthetic organic chemistry. Such molecules are admittedly hard to come by, but when I see them, I marvel at what might be done with them and why people have not considered them more broadly. The other day I was flipping through the 2017 Strem catalog for no logical reason other than I got this shiny new booklet in the mail and felt guilty to toss it straight into the blue recycling bin, the destination of all catalogs I receive on a weekly basis. My attention got piqued by 2-aminoethane-1,1-disulfonic acid (let’s ..read more