No fail no gain

While astronomers recently have been celebrating great discoveries (gravitational waves from colliding black holes keep rolling), at the opposite end of matter size ruler things don’t look as brightly. For instance, the search for ‘sterile’ neutrinos didn’t spot anything, despite the IceCube, a massive 2-km long neutrino detector buried in the Antarctic ice.

Continue reading “No fail no gain”

Skepticism about synaptic nanocolumns

Couple of days ago I’ve come across a recent paper in Nature with quite an eyebrow-raising title “A trans-synaptic nanocolumn aligns neurotransmitter release to receptors“. The title made me think as if the authors have observed hitherto unknown structures in the synaptic cleft. That would be quite a sensation! But then this sentence comes in the abstract:

These presynaptic RIM nanoclusters closely align with concentrated postsynaptic receptors and scaffolding proteins4, 5, 6, suggesting the existence of a trans-synaptic molecular ‘nanocolumn’.

Now it looked like they propose some kind of neuroscience equivalent of dark matter. You know, something that nobody knows what it is, but that certainly must be there, otherwise there’s no explanation to what we see. Continue reading “Skepticism about synaptic nanocolumns”

Extracting ChemDraw schemes as .cdx files from MS Word/Excel/PowerPoint documents

I couldn’t find a free software that would easily do exactly what I want (see the subject). So here’s my ghetto solution, which can be easily automated. Continue reading “Extracting ChemDraw schemes as .cdx files from MS Word/Excel/PowerPoint documents”

Can blog writing get you a real job?

Regular readers of this blog (all five of you, guys) have probably noticed that nothing appeared here in the past two months. As one could guess from the energy conservation law, my activity was mainly concentrated offline during this time. As a quick summary, I have left academia and landed an industry job as a research chemist in a small biotech company. And, quite surprisingly, this blog played a crucial role in this dramatic transition. Continue reading “Can blog writing get you a real job?”

Molecular tribology

It’s hard to imagine more intriguing title in Angewandte Chemie International Edition than “Astringent Mouthfeel as a Consequence of Lubrication Failure“. The first impression doesn’t deceive, and the paper is really interesting and fun to read. Somehow manifestations of molecular interactions in the macroscopic world never stop amusing me. And this communication is exactly about such emergent effect. Continue reading “Molecular tribology”

MedChem shortcuts

Simplification of complex structures is one way medicinal chemists avoid lengthy (and risky) synthetic routes to the analogs of natural products. And it’s absolutely rational, if one can get the same pharmacological effect with a simple molecule, why bother making a complex 3D scaffold? One classic med-chem textbook example is simplification of morphine scaffold to pethidine that led eventually to the development of fentanyl.

morphine-pethidine-fentanyl

Continue reading “MedChem shortcuts”

Pheromone puzzle

A couple of weeks ago I attended a presentation given by Lisa Stowers from Scripps, entitled “Decision-making in the nose: a molecular rationale for the unpredictable nature of female behavior”. The catchy title did its job, so I was there, learning that reaction of female mice on male pheromones depends on (suprise-surprise!) phase of their estrous cycle. The neurobiology behind it is quite amazing, definitely worth reading about. However, my interest was triggered by one question asked after the presentation.

Continue reading “Pheromone puzzle”

OC tidbits #5

Kawamura et al. (Baran lab, Nature)

A paper with a very straightforward title, “Nineteen-step total synthesis of (+)-phorbol” (neither “concise”, nor “efficient”, “elegant” nor any other vague adjective)  was published by Baran lab.

The step that impressed me the most was oxidation of compound 7. Chemo-, regio-, and stereoselectivity of this reaction was “easily predictable based on 100 years of C–H oxidation literature”, according to follow-up blog post, but I wonder how many chemists in the world would bet for this reaction to work so cleanly. Before reading the publication, of course.

TFDO-multistep

Koh et al. (Hoveyda lab, Nature)

Expanding horizons of the metathesis reaction, Hoveyda lab teamed up with Schrock and developed a new catalyst and synthetic methodology for terminal Z-haloalkenes.

metathesis

Battilocchio, Feist et al (Nat Chem)

Remember Morken reaction? I was daydreaming about streamlining it into bond-by-bond stitching of complex compounds. Turns out that Steven Ley was looking in the same direction, although through slightly different chemistry.

sLey

Yang et al. (Org Lett)

mol_gymnastics-ok

A nice example of ‘molecular gymnastics’ (proposed mechanism is quite a funny thing). Heads up from amphoteros blog.

Potter et al (JOC)

Safety first! Opt for hydrosulfate salt next time you prepare a diazotransfer reagent. I didn’t have problems with hydrochloride before, but will better give a try to hydrosulfate.

jo-2016-00177a_0004

Adamo et al (Science)

…but hurry up with your diazotransfer, otherwise machines will soon do it for you! A fridge-sized synthesizer of known pharmaceuticals was constructed by chemists and engineers in MIT. Check out more detailed (and realistic) coverage by Derek Lowe.

 

Chemical Panoptikum #1

Creating new substances, sometimes just for the sake of the creation act itself, is an undeniable part of chemists’ nature. Having flawless analytical data of a newly prepared sample always fills one with mystical joy and feeling of omnipotence. And some chemical creatures are so bizarre that the very fact of their isolation and characterization causes reverence of fellow chemists. So welcome to the chemical Panoptikum, a collection of all sorts of weird structures from the recent literature. Don’t be surprised to meet boron very often here, it’s a really weird element. Continue reading “Chemical Panoptikum #1”

From algae to crystalline sponge

Although not as exciting as it used to be, Fujita’s crystalline sponge technology has reached another milestone. This time the group could determine the absolute configuration of a natural product elatenyneBurton lab from Oxford attempted (and not once) the total synthesis of the product with a sole purpose to assign its structure and absolute configuration. But to achieve that, one needs a good reference analytical data of the natural sample in the first place. And this was the bottleneck for the featured compound. Owing to its almost symmetrical structure, the molecule doesn’t rotate the polarized light by a lot (the latest [α]D values from Burton and Kim labs were −1.6° and +0.80° for two enantiomers). But reported data for ‘natural’ elatenyne varied from +19° to −10°. Which would make ambiguous even a qualitative judgement about the synthesized compound.

elatenyne.png
Structure of elatenyne is almost σ-symmetric

And as you can imagine, the molecule doesn’t easily crystallize in a conventional way. So it was an ideal case to try soaking a crystalline sponge in a solution of the compound. Remarkably, Fujita’s group needed only 5 μg of the freshly isolated compound for the analysis. As the result, they confirmed that Burton’s structure was correct.

No comments on bioactivity though.