Electrifying chemistry...
La Jolla, CA
Joined January 2014
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Radical cross-coupling, simplified. No specialized equipment. No exogenous redox. No stoichiometric organometallics. The best part is no part.
A perspective on the field, appearing today in @ChemRxiv : chemrxiv.org/doi/full/10.264…
Baran Lab retweeted
💥 Introducing Warp Sciences, a new company applying AI and robotics to help the world develop new medicines faster.
We’ve raised a $215M Series A led by @lightspeedvp to bring frontier AI out of the browser and into the lab, and build scientific capacity here in America.
I co-founded Warp with my long-time friend @dpatil, FAIR co-founder @manohar_paluri, and drug hunter Sol Reisberg. The early team is full of incredible people like @bkspears9, who helped achieve Q>1 fusion at LLNL.
Final version appearing today in new @ACSPublications journal ACS Applied Catalysis: pubs.acs.org/aacabd/article/…
Two directions. One radical move.
Simultaneous two-directional catalytic radical cross-coupling, a great collaboration with Abbvie (@KaidHarper), is out now in @ChemRxiv (chemrxiv.org/doi/full/10.264…)
Diacid-derived bis-RAEs undergo Ag–Ni electrocatalytic decarboxylative arylation → functionalized dibenzyl amines & linkers.
Diamine-derived bis-sulfonyl hydrazides deliver redox-neutral deaminative RCC → decorated carbon skeletons.
Chemoselective. Scalable. Modular access to valuable products from simple, symmetrical starting materials — including PROTAC-style linkers with C–C bonds instead of amides.
The classic two-directional logic of @SchreiberStuart, now fully radical.
Stop sampling accessible isomers. Start building the target matrix.
Saturated heterocycles bearing covalent reactive groups already appear in more than a dozen FDA-approved medicines, including ritlecitinib and ibrutinib, making systematic exploration of this space directly relevant to medicine. When covalently reactive molecules are screened by proteomics to discover new protein engagements, the relevant unit of design is no longer a single compound—it is the complete set of regio- and stereoisomers of a privileged scaffold. Incomplete libraries, constrained by synthetic bias, systematically miss the very interactions they set out to find.
Radical cross-coupling removes that constraint. By pairing stereorandomizing and stereopreserving manifolds from simple commercial precursors, we constructed exhaustive piperidine (40) and pyrrolidine (24) matrices and expanded the collection to 108 covalent stereoprobes. Proteome-wide ABPP revealed highly differentiated, stereoselective engagements that further diversified with the choice of covalent reactive group. Selected hits were characterized by X-ray, and protein-directed ABPP expanded the observable ligandability landscape still further.
A collaboration with @VividionRx and the Cravatt lab, appearing today in @ChemRxiv: chemrxiv.org/doi/full/10.264…
Wow—this is a spectacular demonstration of what targeted covalent stereoprobes can unlock: biorxiv.org/content/10.64898…
Huge congratulations to the Merbl lab and especially to Bruno Melillo and colleagues for identifying a selective covalent ligand for a dynamic pocket in the non-catalytic proteasome regulator PSME4. The finding that blocking or reducing PSME4 stabilizes STAT1, restores interferon-associated transcription, enhances antigen presentation, and suppresses tumor growth in vivo defines a beautiful PSME4–STAT1–STAT3 axis that couples proteasome composition to tumor immunity.
Exactly the kind of proteome-wide discovery that becomes possible when chemical biology is paired with rigorous functional follow-up.
Baran Lab retweeted
Happy to share our latest work out now in @NatureChemistry. We show the cross coupling of alkyl carboxylic acids and boronic acids.
Congrats to Jessica, @ortho_maxb, and the team! @NUChemistry
Link: nature.com/articles/s41557-0…
Baran Lab retweeted
Resolving
Structural Ambiguity through Total Synthesis:
Evolution of a Synthetic Strategy for Secalosides A and B pubs.acs.org/jacsat/article-…
Baran Lab retweeted
Happy to share our Total Synthesis
of (−)-Methyl Gummiferolate @J_A_C_S. Pattern recognition identified key starting materials and again the BROC chemistry @BaranLabReads formed key C-C bond and stereocenters. Congratulations to Weizhao and Jingsong!
pubs.acs.org/jacsat/article/…
Baran Lab retweeted
From dynamic tautomers to stable isosteres. Our electrochemical method converts readily available CF₃ alkenes into independently accessible fluorinated isosteres corresponding to keto and enol forms. Now out in JACS! doi.org/10.1021/jacs.6c15284
Final version out today in @NatureSynthesis : nature.com/articles/s44160-0…
Ni-Catalyzed C–H Alkylation of (hetero)arenes: Super simple, broad scope, enabled by sulfonylhydrazides! Appearing today in @ChemRxiv (chemrxiv.org/engage/chemrxiv…). An awesome joint venture with the amazing @EngleLab.
Quick Summary:
A new method for facile C–H alkylation of a range of (hetero)arenes is described using Ni-catalysis. This reaction takes place at 50 °C, is scalable, tolerates heterocyclic substrates, and can be applied to both primary and complex secondary alkyl donors. Success hinges on the use of sulfonylhydrazide-based alkyl donors that mildly generate alkyl radicals thereby obviating the need for alkyl halide precursors that require more harsh conditions to activate. The demonstrated substrate scope is broad (>70 examples), and the reaction was also applied to natural product synthesis. Mechanistic studies (both computational and experimental) suggest that an asynchronous, amine-assisted C–H activation pathway is operative which may have larger implications for the field.
Baran Lab retweeted
Skip the Mitsunobu, go straight to the hydrazide.
Our growing collection of sulfonyl hydrazides are the cheapest on the market and get to your bench quickly with same-day shipping.
#knightchem #medchem #sulfonylhydrazides
Baran Lab retweeted
The final version of our work is now online in JACS!
Scalable total synthesis of nonthmicin and ecteinamycin revealed a dual antibacterial and antitoxin profile against Clostridioides difficile.
Many thanks to all our collaborators! pubs.acs.org/jacsat/article/…
Our latest work shows how modern total synthesis can enable therapeutically meaningful discovery, uncovering selective anti-C. difficile activity and toxin-protective effects of structurally complex polyether ionophores. Now available on ChemRxiv: chemrxiv.org/doi/full/10.264…
Baran Lab retweeted
Scripps Research, @UCLA and @SuntheticsML have received a $19.5M @NSF award to establish a nationally accessible, fully automated chemistry lab. The AI-enabled “Chemistry Node” will serve as a discovery engine and training tool for a new generation of chemists.
More: ow.ly/Zcne50ZFQxA
Baran Lab retweeted
Here comes a short review on the current state of electrochemical hydrogenation of arenes and heteroarenes, with a particular focus on how electrochemistry can precisely control partial vs. full reduction of the targeted aromatic rings.
Open access link: sciencedirect.com/science/ar…
Baran Lab retweeted
Our latest paper is now out in @J_A_C_S!
Carbenoid species have had a profound impact on synthetic chemistry and are now indispensable tools for building molecular complexity. Yet one of their smallest main-group relatives, the borylene, has remained notably absent from the synthetic chemist’s toolbox, despite its fascinating and highly unusual electronic structure.
Since starting our group, one of our major goals has been to address this challenge and explore the synthetic potential of borylenes.
In our work, we report an exceptionally mild and modular approach to borylene generation from simple, readily diversifiable precursors. We then use this platform to explore the cycloaddition chemistry of borylenes with alkenes, providing access to unique fused borirane architectures.
This reactivity developed into a chemo- and regioselective strategy for alkene functionalization, with the resulting boriranes serving as versatile synthetic intermediates. We further demonstrate its utility through application to the formal synthesis of natural products.
We believe this work takes borylenes one step closer to becoming practical species for synthetic chemistry, and opens the door to many new transformations yet to be discovered.
pubs.acs.org/jacsat/article/…
Two directions. One radical move.
Simultaneous two-directional catalytic radical cross-coupling, a great collaboration with Abbvie (@KaidHarper), is out now in @ChemRxiv (chemrxiv.org/doi/full/10.264…)
Diacid-derived bis-RAEs undergo Ag–Ni electrocatalytic decarboxylative arylation → functionalized dibenzyl amines & linkers.
Diamine-derived bis-sulfonyl hydrazides deliver redox-neutral deaminative RCC → decorated carbon skeletons.
Chemoselective. Scalable. Modular access to valuable products from simple, symmetrical starting materials — including PROTAC-style linkers with C–C bonds instead of amides.
The classic two-directional logic of @SchreiberStuart, now fully radical.
Baran Lab retweeted
"Doubly Decarboxylative Asp-Asp Stapling” appearing today in @ChemRxiv : chemrxiv.org/doi/full/10.264…
Collaboration with @nagata_yuuya
Baran Lab retweeted
When I was in grad school, radicals were synonymous with “messy and uncontrollable”. Modern radical-cross coupling tells almost the opposite story. And the field is still evolving into a new phase. A great review of how far it has come!
Radical cross-coupling, simplified. No specialized equipment. No exogenous redox. No stoichiometric organometallics. The best part is no part.
A perspective on the field, appearing today in @ChemRxiv : chemrxiv.org/doi/full/10.264…
Baran Lab retweeted
Really excited to see this Perspective out today! 🚀
Radical cross-coupling carried a hidden tax: redox. Sulfonyl hydrazides changed that paradigm by bringing their own electrons 🎉
Two years later: what comes next and can radical cross-coupling become as intuitive as a Suzuki?
Radical cross-coupling, simplified. No specialized equipment. No exogenous redox. No stoichiometric organometallics. The best part is no part.
A perspective on the field, appearing today in @ChemRxiv : chemrxiv.org/doi/full/10.264…