Dirk Trauner

Dirk Trauner

@dirktrauner.bsky.social

Penn Integrates Knowledge Professor, Natural Product Aficionado, Photopharmacologist, Fox Terrierist, Book Lover, and Unfulfilled Architect. #firstgen

3.4K followers4.1K following73 posts

Dirk Trauner reposted

Cornelius Gati
@gati.bsky.social

Our AM-3 paper is out in Cell. Opioids are indispensable therapeutics, but have severe side effects. Because they are administered systemically, it is hard to dissect how they work, and to separate side effects. So we built one you can switch on and off with light. 🧵 www.cell.com/cell/abstrac...

Dirk Trauner
@dirktrauner.bsky.social

Check out our latest paper on efficacy photoswitches that can locally light up opioid receptors, thus avoiding unwanted central and peripheral side effects (respiratory depression, constipation). www.cell.com/cell/fulltex...

cell.comAn opioid efficacy switch for reversible optical control of analgesiaAzo-morphine-3 (AM-3) is a photoswitchable ligand that toggles between low and high efficacy states to control mu-opioid receptor activity in vitro and in vivo both in the brain and periphery. AM-3 pr...
Dirk Trauner
@dirktrauner.bsky.social

Stephadiamine, take two. A second synthesis is justifiable if you (a) radically change the strategy and (b) develop new methodology along the way. Congratulations, Ana Vi, on bringing this one home! pubs.acs.org/doi/10.1021/...

pubs.acs.orgConcise Synthesis of (±)-Stephadiamine via Vinylogous Wenker CyclizationA short and diastereoselective synthesis of stephadiamine is presented. The carbocyclic framework of the alkaloid was built in the opening step through a homoconjugate addition–Wittig olefination cascade with a modified Schweizer–Fuchs cyclopropyl phosphonium salt. The challenging aza[4.3.3]propellane was subsequently installed through a vinylogous substitution of an allylic hydroxy group with a primary amine that was developed for the purposes of the synthesis. After a series of oxidations, a second α-tertiary amine was introduced through a diastereoselective Strecker reaction, thus establishing the syn-diamine motif. Finally, an undesired retro-Strecker pathway was circumvented by using an azide functionality to mask the primary amine during a late-stage lactonization, thus enabling the completion of the synthesis in 12 steps.
Dirk Trauner
@dirktrauner.bsky.social

Silyl protecting groups can function as dispersive directing groups, leading to unexpected stereoselectivities! Collaborating with Robert Paton, we have demonstrated this for a specific case. Stay tuned for a more systematic study! pubs.acs.org/doi/full/10....

pubs.acs.orgProtecting Groups as Dispersive Directing Groups: Toward the Asymmetric Synthesis of AltemicidinWe report progress toward the asymmetric total synthesis of altemicidin, a monoterpene alkaloid featuring a 6-azatetrahydroindane core. A diastereoselective 1,3-dipolar cycloaddition with TMS-diazomethane enabled the construction of a key pyrazoline intermediate. Computational analysis (EDA/NCI) revealed attractive London dispersion forces as the origin of the unexpected stereoselectivity. An effective method to convert the initial silylated 1-pyrazoline into a stable 2-pyrazoline was developed. Selective reductive trifluoroacetylation and SmI2-mediated N–N bond cleavage afforded a 1,3-diamine suitable for further functionalization.
Dirk Trauner
@dirktrauner.bsky.social

Vitamin D is famous for its photochemistry. We have now added a photopharmacology aspect in a wonderful collaboration with the Merk group. onlinelibrary.wiley.com/doi/full/10....

onlinelibrary.wiley.comAn Agonist/Antagonist Photo‐Switchable Vitamin D Mimetic Enables Bidirectional Optical Control of VDRVitamin D exhibits complex and cell-specific biological effects in multiple tissues via activation of the ligand-sensing transcription factor vitamin D receptor (VDR). The photo-switchable vitamin D ...
Dirk Trauner
@dirktrauner.bsky.social

A big step forward in Photopharmacology, just published in Nature Medicine: nature.com/articles/s41... A compound we conceptualized in 2008 (PMCID: PMC4040390) and synthesized in 2010 (PMCID: PMC3401033) proves effective in human vision restoration.

nature.comIntravitreal photoswitch therapy in advanced retinitis pigmentosa: a phase 1 open-label trial - Nature MedicineA first-in-human phase 1 trial shows that intravitreal photoswitch therapy can be administered safely in advanced retinitis pigmentosa, with exploratory signals compatible with light responsiveness fo...
Dirk Trauner
@dirktrauner.bsky.social

Opticial Control of Cholesterol, attempting to stay as close to the original as possible. Congratulations to Michael Zott, who defined and spearheaded this study, and to our wonderful collaborator Luca Laraia!

Luca Laraia@lucalaraia.bsky.social

Delighted to have collaborated with the @dirktrauner.bsky.social lab on the development and characterisation of #photoswitchable #cholesterol derivatives, now out in @jacs.acspublications.org! (1/3) pubs.acs.org/doi/full/10....

pubs.acs.orgDevelopment of Photoswitchable Cholesterol Derivatives through Side Chain ReplacementCholesterol is ubiquitous in biology, shaping membrane properties and serving as a biosynthetic precursor for essential signaling molecules and hormones─and, in some contexts, acting as a signaling mo...

Dirk Trauner reposted

Luca Laraia
@lucalaraia.bsky.social

Delighted to have collaborated with the @dirktrauner.bsky.social lab on the development and characterisation of #photoswitchable #cholesterol derivatives, now out in @jacs.acspublications.org! (1/3) pubs.acs.org/doi/full/10....

pubs.acs.orgDevelopment of Photoswitchable Cholesterol Derivatives through Side Chain ReplacementCholesterol is ubiquitous in biology, shaping membrane properties and serving as a biosynthetic precursor for essential signaling molecules and hormones─and, in some contexts, acting as a signaling mo...
Dirk Trauner
@dirktrauner.bsky.social

[6+4] Cycloadditions! Introducing our first dive into this fascinating subject in a very enjoyable collaboration with Ken Houk and his team. Congrats to Harrison and Tufan! pubs.acs.org/doi/10.1021/...

pubs.acs.orgSynthesis of Collinoketones via Biomimetic [6 + 4] CycloadditionCycloadditions are among the most powerful reactions for constructing molecular complexity. The archetypal example is the [4 + 2] (Diels–Alder) cycloaddition, which efficiently furnishes cyclohexene d...
Dirk Trauner
@dirktrauner.bsky.social

As my memory is not as good anymore as it once was, I am excited to share this exciting collaboration with Cristina Alberini (NYU) with you: www.nature.com/articles/s41...

nature.comA prodrug targeting CIM6P/IGF2R enhances memory in healthy mice and reverses deficits in an Angelman syndrome mouse model - Translational PsychiatryTranslational Psychiatry - A prodrug targeting CIM6P/IGF2R enhances memory in healthy mice and reverses deficits in an Angelman syndrome mouse model
Dirk Trauner
@dirktrauner.bsky.social

It has been quite an emotional week for me — first, reconnecting with my Berkeley past, and then looking to the future by celebrating with my former graduate student Nina Hartrampf. Congrats, Nina, and, yes, "Peptide können alles!"

Helvetica Chimica Acta@helvchimacta.bsky.social

@ninahartrampf.bsky.social gives the award talk (@dechema.bsky.social prize 2024) ‚Flow-Based Synthesis of Post-Translationally Modified Peptides and Proteins‘ at the #UniZH. Congratulations to our ECAB member!!

Dirk Trauner reposted

Johannes Morstein
@morstein.bsky.social

Excited to share our new @pubs.acs.org paper! We engineered cells with ~10% photolipids in the ER membrane. This enabled optical control of membrane viscosity to study its impact on ER→Golgi protein transport. @dirktrauner.bsky.social @noemijimenezrojo.bsky.social pubs.acs.org/doi/10.1021/...

pubs.acs.orgOptical Control of Membrane Viscosity Modulates ER-to-Golgi TraffickingThe lipid composition of cellular membranes is highly dynamic and undergoes continuous remodeling, affecting the biophysical properties critical to biological function. Here, we introduce an optical a...
Dirk Trauner
@dirktrauner.bsky.social

Just out: Our collaboration with Eric Schelter & Randall Wilharm on parsing the fascinating photochemistry of lanthanides with azobenzene photoswitches. A deep dive into light and rare earths en route to more efficient separations. pubs.acs.org/doi/10.1021/...

pubs.acs.orgBreaking a Lewis Acidity Trend for Rare Earths by Excited State QuenchingFacilitating different chemistries between the rare earth (RE = La–Lu, Sc, Y) ions is of significant interest for their separations. While the bulk of attention has been on maximizing the small differ...
Dirk Trauner
@dirktrauner.bsky.social

I had a great time at the University of Rochester as the Victor Chambers Lecturer! And I really enjoyed the amazing George Eastman House and Museum, built by a millionaire (nowadays billionaire) who was civic minded and kept a low profile.

Dirk Trauner
@dirktrauner.bsky.social

Ready to take off as a synthetic chemist? Check out this tutorial review we wrote with Frank Glorius and Jasper Tyler!

Frank Glorius@gloriusfrank.bsky.social

Scholarly review written by @DirkTrauner and @GloriusGroup: Reaction development: a student's checklist📜☑️😀 Published in Chem. Soc. Rev. doi.org/10.1039/d4cs...

doi.orgReaction development: a student's checklistSo you’ve discovered a reaction. But how do you turn this new discovery into a fully-fledged program that maximises the potential of your novel transformation? Herein, we provide a student's checklist...
Dirk Trauner
@dirktrauner.bsky.social

Dearomative Diels-Alder reactions are currently hot in total synthesis. They go back to Peter Yates (who trained my mentor Sam Danishefsky). And the Wessely reaction was also discovered in Vienna :)

Dirk Trauner
@dirktrauner.bsky.social

My first chemistry professor in Vienna, Erich Zbiral, shall not be forgotten. Everybody loves the Tanabe-Eschenmoser Fragmentation but the analogous Zbiral-Fragmentation of epoxy vinyl azides is equally cool.

Dirk Trauner
@dirktrauner.bsky.social

Zbiral was also one of the first chemists to work on sialic acid. We had to obtain it through hydrolysis of meconium, the stuff newborns excrete in their first days. It contains large amounts of polysialic acid. Later, we switched to Chinese birds' nests. Fun times!

Dirk Trauner
@dirktrauner.bsky.social

And here is a challenge to you sialyl aficionados: Why do newborns excrete polysialic acids? Where does it come from? From polysialylated GPCRs? Can’t be on that scale. I never found that answer.

Dirk Trauner
@dirktrauner.bsky.social

Azorellolide! How can you not work on a natural product that starts with "Azo"? I have to say my respect for carbocations has enormously gown through this project. They are just too high in energy and have too many options. But you can tame them! pubs.acs.org/doi/10.1021/...

pubs.acs.orgBiomimetic Synthesis of Azorellolide via Cyclopropylcarbinyl Cation ChemistryA concise synthesis of the complex diterpene azorellolide, inspired by speculations on biosynthetic cationic cascades, is presented. The approach, guided by computation, relies on the intramolecular interception of a cyclopropylcarbinyl cation by an appended carboxylate. The successful execution of this strategy was achieved through acid-catalyzed isomerization of a β-lactone in competition with a type I dyotropic rearrangement.