Alex Solivan

A DNA‐Encoded Chemical Library Incorporating Elements of Natural Macrocycles Making millions: Inspired by polyketide and mixed peptide-polyketide natural products, a DNA-encoded macrocycle library with rich backbone diversity has been developed. The library comprises millions...

I’m a fan of this paper from Gillingham that looks at some macrocyclic DELs as a more standard pick (onlinelibrary.wiley.com/doi/full/10....) and this work on a protein-templated DEL system might be an interesting curveball!
www.nature.com/articles/s41...

You’ve heard of ubiquitination, meet deazaguanylation: Doug Wassarman in our lab discovered phage defense pathways have co-opted Q nucleobase biosynthetic enzymes to catalyze a new form of protein conjugation chemistry @science.org

www.science.org/doi/10.1126/...

“Hypervalent iodide giveth and hypervalent iodide taketh away”

Well it’s chemistry of course. The reason why organic chemists historically make p-tosylates rather than the simpler benzenesulfonates is that p-tosyl chloride is a cheap byproduct from saccharin synthesis. The ortho isomer is used for saccharin. #chemsky 🧪

>1700 examples???

SNAP-tag2 for faster and brighter protein labeling - Nature Chemical Biology SNAP-tag is a widespread tool for labeling protein for bioimaging. Now, Kühn et al. report SNAP-tag2 with increased labeling kinetics and brightness, which translates into a better performance in live...

Finally out in Nature Chem Bio:
SNAP-tag2 for faster and brighter protein labeling
www.nature.com/articles/s41...
Thank you Steffi and Veselin.

How do you turn a carbonyl into sulfur?

In this work, Zining from our lab developed a carbonyl-to-sulfur swap enabled by a rationally designed N′-alkyl-hydrazonamide (NAHA) reagent that promotes double C-C bond activation.

www.science.org/doi/10.1126/...

Seems a good time to post the “Top types of med chem papers” #ChemSky

Yeah it’s currently cold enough in my building (heater is down) that the dmso spontaneously froze when I started pipetting which 100% didn’t help with my 3mm tube problem

Never am I more convinced that I angered an eldritch god in a past life than when I’m trying to pipette a sample in dmso-d6 into a 3mm NMR tube #chemsky

Ooh I might steal this shade of green y’all use…

I was having a hard time describing how a plate of cultured cells didn’t look healthy to a new undergrad in the lab. He looked at them and said, “oh yeah, the vibes are off.” Thank god for Gen Z.

Escherichia coli ribosomes support translation of (R) and (S) β2-hydroxyacids in vitro: a structural and biochemical study The ribosomal incorporation of backbone-modified amino acid analogs into peptides and proteins enables the programmed synthesis of sequence-defined biopolymers with tunable properties. However, the su...

Check out our latest preprint describing two structures of ribosomes complexed with the two enantiomers of a β2-hydroxy acid. Our structures show that despite stereochemical differences, both are ultimately well positioned for bond formation within the ribosome!
chemrxiv.org/engage/chemr...

Wait that’s interesting. Different type of system I think but still very cool. Also I love the phrase “polymer lore”

For an article in the 1970s to specify a reagent was “cautiously added” is really something…

Will update if I can get this route to work 😭

Amazing!! Thank you!!

Hmm wait that makes sense. Ok I might just push the NaN3 route forward and see if adding an external lewis acid gets me similar reactivity in the aggregate. Worst case scenario I make the lithium azide…

Maybe this is a shout into the void but any thoughts on why someone would choose to use lithium azide over sodium azide to ring open an epoxide? Like every lit precedent cites the same original synthetic route and one group even goes about making LiN3 from NaN3. Kinda at a loss

Oh this wasn’t even the example I was thinking of but you just reminded me of a set of papers I saw that “improved” on a lanthanum triflate catalyzed reaction by switching to Pb(NO3)2

Ah we love a classic case of “is this unstable, toxic, and generally annoying reagent *actually* necessary to get this rxn to work or is it just how the first guy did it and no one bothered to change it in the last 30 years??”

:))) #chemsky

If you're interested in a break from the doom-and-gloom, may I recommend our article, online today @nature.com

A solution to the pyrazole alkylation problem, leveraging S-to-NR atom replacement. Skeletal editing has strategic value, outside of late-stage!

www.nature.com/articles/s41...

📰 Great "First Reactions" by @aprillukowski.bsky.social featuring C-GEM's recent thioribose work!

pubs.acs.org/doi/10.1021/...

Phosphate-enabled mechanochemical PFAS destruction for fluoride reuse - Nature This study highlights a protocol that converts various perfluoroalkyl and polyfluoroalkyl substances (PFASs), including fluoroplastics, into valuable fluorochemicals through a solvent-free mechan...

Fluorochemical synthesis directly from PFAS is insane. Beautiful beautiful work from the Gouverneur group #chemsky

(Strategies to bypass HF? Now chemistry to enable a circular fluoride economy? When do the conversations about Nobels tend to begin…)

www.nature.com/articles/s41...

Ohhh haven’t given too much thought into mixed solvents so I’ll get back to you if I end up trying that but switching to iPrOH is honestly a great idea, idk why I was trying to force it into ethanol

Set up my initial attempts in EtOH with cyclohexane as a vapor diffusion cosolvent but not holding my breath

Definitely not freely in ether, moderate solubility in DCM/EA. EtOH/ACN were better but still not great

a man with a mustache is sitting on a swing in a park ALT: a man with a mustache is sitting on a swing in a park

Stuck waiting for crystals to assign absolute stereochem. Any secret magic conditions for very polar compounds that are somehow also surprisingly greasy?

Woahhhh

Talk about a game changer from the Baran lab #chemsky

Usually HATU, PyBOP, and EDC will get me through 95% of my couplings and TCFH-NMI tends to blast through the remaining tricky ones