NaOH Bartfield

Thanks scott!

Total Synthesis of Chartelline C Chartellines are cytotoxic marine alkaloids that were isolated in the late 1980s. Their unique, heavily oxidized structures, comprising a spirocyclic β-lactam, a halogenated indolenine, a chloroenamide, and a 2-haloimidazole, have motivated extensive efforts toward their synthesis. However, only a single synthesis of any chartelline has been reported in the nearly 40 years since their isolation. Here, we describe a route to chartelline C (3) from the macrolactam 21, an intermediate we employed en route to the related securine and securamine alkaloids. The key challenges in converting macrolactam 21 to chartelline C (3) involve stereocontrolled construction of the C2–C3 enamide, isomerization of the trans-C10–C11 alkene, formation of the strained spirocyclic β-lactam, and chlorination of the enamide. Each of these challenges was addressed by an unconventional approach. The macrolactam 21 was converted to cis-enamide (2Z,10E)-24 by in situ masking of the C12 ketone, followed by stereoselective acid-catalyzed elimination of the C2 carbinolamide. The C10–C11 trans-alkene was isomerized by a photolytic process; control experiments suggest that this isomerization occurs by energy transfer. The β-lactam was constructed by a solid-state reaction involving the adsorption of the bromoindolenine 26 onto activated basic alumina. Late-stage enamide chlorination, which had been an obstacle in prior approaches, was accomplished by a novel photoredox-mediated halogenation. These latter studies suggest that N-haloanomeric amides and N-haloguanidines may act as halogen atom transfer agents under thermal or photolytic conditions. Finally, we show that chartelline C (3) reacts with sulfur-based nucleophiles, suggesting that further studies of their biological activity may be warranted.

More top-notch natural product synthesis from the Herzon lab
Incredible work from Brandon Alexander and @naohbartfield.bsky.social Now in @jacs.acspublications.org ASAP

Total Synthesis of Chartelline C Chartellines are cytotoxic marine alkaloids that were isolated in the late 1980s. Their unique, heavily oxidized structures, comprising a spirocyclic β-lactam, a halogenated indolenine, a chloroenamide, and a 2-haloimidazole, have motivated extensive efforts toward their synthesis. However, only a single synthesis of any chartelline has been reported in the nearly 40 years since their isolation. Here, we describe a route to chartelline C (3) from the macrolactam 21, an intermediate we employed en route to the related securine and securamine alkaloids. The key challenges in converting macrolactam 21 to chartelline C (3) involve stereocontrolled construction of the C2–C3 enamide, isomerization of the trans-C10–C11 alkene, formation of the strained spirocyclic β-lactam, and chlorination of the enamide. Each of these challenges was addressed by an unconventional approach. The macrolactam 21 was converted to cis-enamide (2Z,10E)-24 by in situ masking of the C12 ketone, followed by stereoselective acid-catalyzed elimination of the C2 carbinolamide. The C10–C11 trans-alkene was isomerized by a photolytic process; control experiments suggest that this isomerization occurs by energy transfer. The β-lactam was constructed by a solid-state reaction involving the adsorption of the bromoindolenine 26 onto activated basic alumina. Late-stage enamide chlorination, which had been an obstacle in prior approaches, was accomplished by a novel photoredox-mediated halogenation. These latter studies suggest that N-haloanomeric amides and N-haloguanidines may act as halogen atom transfer agents under thermal or photolytic conditions. Finally, we show that chartelline C (3) reacts with sulfur-based nucleophiles, suggesting that further studies of their biological activity may be warranted.

Our approach to the total synthesis of chartelline C, out now in JACS. Photochemistry and unique topology gave way to some really interesting reactivity!

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

Aw thanks buddy

Yeah this is really sick work

Lol

Always a great conference with student presentations, talks from Boehringer, Merck, BMS, Pfizer and keynotes from Martin Tomanik (NYU) and Ryan Shenvi (Scripps) @shenvi.bsky.social
(And yes, @naohbartfield.bsky.social is one of the student speakers)
June 27 @ Conn College New London CT

ACS CVS tomorrow! I'm hyped! Can't wait to see @naohbartfield.bsky.social 's talk and try to annoy @bagphos.bsky.social !!!

Post from Tw*tter:

Happy Pride month 🏳️‍🌈

Trans people are being targeted, excluded, and killed simply for being themselves.

Kick off this month by considering the hire of trans workers if you're in the position, or donating to the Transgender Law Center (transgenderlawcenter.org/donate/) if you can

Super cool as always!

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...

My boss is Seth Herzon in case people want to go for him instead of me

Boss is talking about my PhD work on Wednesday morning in room 30E if yall wanna tune in 👀

Boss is talking about my PhD work on Wednesday morning in room 30E if yall wanna tune in 👀

Headed to the @acs.org meeting in San Diego? Make sure to set the time zone in your app/online schedule to Pacific Time!! #ACSSpring2025 #ChemSky

Trump Pulled $400 million From Columbia. Other Schools Could Be Next. The administration has circulated a list that includes nine other campuses, accusing them of failure to address antisemitism.

This is going to do absolutely nothing to curb antisemitism and will, if anything, make things worse.

Smokescreen after smokescreen for attacks on universities. All of us whose university is not on this list cannot breathe a sigh of relief - we will not be spared.

www.nytimes.com/2025/03/08/u...

Do they call it a "Roman Salute" on this app too or can we just soberly call them Nazis on Bluesky

Some of those replies are the equivalent of:
“To keep my electrolytes in balance I only use aqueous n-butyl lithium for deprotonation”

I am currently experiencing antisemitism on twitter dot com for telling people not to drink methylene blue 🫡

things are looking mighty reichy right now

Infinite

Yeah sure why not 🫡

Not this time 😭

Just got a 4% yield on something i was convinced was impossible and yknow what i'll take it

Hey science friends?

I know that many of you are concerned about the perceived neutral and apolitical role of science in decisionmaking.

But scientists are being targeted. We didn't start it.

And advocating *for the role of scientific evidence in policymaking* is not unprofessional advocacy.

I think science communicators do a great job. I do not think you can out-science-communicate fascist ideology. Its on a whole different axis of logic

Colombian President Gustavo Petro's full post ordering an increase of import tariffs on U.S. goods, says he doesn't really like traveling to the U.S. because it's “a bit boring” and invokes the ancestors

The future was supposed to have flying cars, not AI John McAfee coming back from the dead to promote a scam crypto coin