
New copper-catalyzed C-H activation strategy from Scripps Research Two-mode reactions inspired by human detox enzymes offer powerful new tools for drug discovery and optimization
April 19, 2024
LA JOLLA, CA Inspired by what human liver enzymes can do, Scripps Research chemists have developed a new set of copper-catalyzed organic synthesis reactions for building and modifying pharmaceuticals and other molecules. The new reactions are expected to be widely used in drug discovery and optimization, as well as in other chemistry-based industries.
In their study, which initially published in an unedited version on March 28, 2024, in Nature, the chemists showed that their new methods can be used to perform two modifications called dehydrogenations and lactonizations on a broad class of inexpensive starting compounds. The reactions require only a simple copper-based catalyst, whereas related reactions typically require much more cumbersome and expensive methods though this specific type of reaction was previously inaccessible by any organic synthesis method.
This new two-mode approach could be particularly useful for late-stage modifications and diversifications of natural products and drug molecules, says study senior author Jin-Quan Yu, PhD, Frank and Bertha Hupp Professor of Chemistry and Bristol Myers Squibb Endowed Chair in Chemistry at Scripps Research.
The study's first authors were postdoctoral research associate Shupeng Zhou, PhD, and doctoral student Annabel Zhang, PhD, both of the Yu lab during the study.
The initial goal of the research was to find a new and better method for what chemists call carbon-hydrogen (CH) activation, in which a hydrogen atom on the carbon backbone of an organic compound is detached and replaced with something else a valuable tool for drug synthesis.
In this case, the Yu lab which has a history of innovations in CH activation chemistry sought a better way to do CH activations that replace the hydrogen with an oxygen atom. This is a common transformation in the construction or modification of biologically active molecules, though chemists haven't had laboratory methods for doing it that are as simple, direct and broadly useful as they would like.
Yu and his team looked to nature for inspiration, in particular to cytochrome P450 enzymes, which are found in most living organisms, and help clear potentially toxic molecules in the human liver. Cytochrome P450 enzymes perform oxygen-for-hydrogen reactions very efficiently. Some of these enzymes have the additional ability to catalyze a different hydrogen-removal process called dehydrogenation, which can be used to strip hydrogens from two carbons simultaneously, allowing other atoms or clusters of atoms to replace them. The chemists set themselves the ambitious goal of finding a general organic synthesis method for doing either the oxygenation or dehydrogenation reaction, as these versatile bimodal enzymes do in living cells.
After months of experimentation, Yu's team found that, through chemical transformations similar to those done by the bimodal cytochrome P450 enzymes, they could efficiently make compounds called unsaturated primary amides a class that includes many drug molecules by dehydrogenating inexpensive starting compounds called methoxyamides. For the catalyst, they needed only copper fluoride also inexpensive and easy to use.
As the chemists explored the breadth of their new dehydrogenation method using different specific starting compounds, they observed trace amounts of a type of molecule called a lactone, indicating that an oxygenation reaction had occurred. Ultimately, they were able to determine the reaction conditions that favored this oxygenation or lactonization over the dehydrogenation. In other words, like the bimodal enzymes that had inspired them, they were able to control whether their approach led down one reaction path or the other.
The team demonstrated the remarkable versatility of this set of reactions by using it to modify via dehydrogenation or lactonization, or both a wide variety of starting compounds, including the neurological drug valproic acid and the cholesterol-lowering drug gemfibrozil. (Modifications of existing complex molecules to create potentially better variants are a common drug discovery and optimization technique.)
Yu and his group are currently developing a similar approach for making and modifying lactone- and amide-related compounds called lactams, which include some antibiotics.
We've already had a lot of interest in this new approach from pharma industry chemists, Yu says.
Copper-catalyzed dehydrogenation or lactonization of C(sp3) H bonds was co-authored by Shupeng Zhou, Zi-Jun Zhang and Jin-Quan Yu.
Support for the research was provided by the National Institutes of Health (2R01GM084019).
Chemistry Yu, Jin-Quan
North America Stories
18/03/2026
SMPTE Unveils 2026 NAB Show Educational Presentations
Brie Clayton March 18, 2026
0 Comments
SMPTE , the home of media professionals, technologists, a...
18/03/2026
Auditel Ad Campaign Shot on Blackmagic PYXIS 12K
Brie Clayton March 18, 2026
0 Comments
LED wall virtual production blends 12K open gate acquisition w...
18/03/2026
Brainstorm transforms productivity and sustainability with Suite 7 at NAB Show 2...
18/03/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
18/03/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
18/03/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
18/03/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
18/03/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
18/03/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
18/03/2026
SMPTE , the home of media professionals, technologists, and engineers, today unveiled its educational presentations for the 2026 NAB Show. This year SMPTE will ...
18/03/2026
Maxon, maker of powerful, approachable software solutions for creators working in 2D and 3D design, motion graphics, visual effects, gaming, and more, today ann...
18/03/2026
Digital Alert Systems
Preview
2026 NAB Show
April 19 - 22
Booth C3452
At the 2026 NAB Show, Digital Alert Systems will showcase Version 6.0 of its DASDEC ...
18/03/2026
Setplex today announced that it will showcase its complete, fully integrated Zapflex platform for the first time at the 2026 NAB Show, introducing powerful new ...
18/03/2026
COW Jobs: Seeking DP for Low Budget Dramedy - Chicago
Brie Clayton March 17, 2026
0 Comments
Seeking Director of Photography for Low Budget Dramedy Fe...
18/03/2026
COW Jobs: Seeking Gaffer for Low Budget Dramedy - Chicago
Brie Clayton March 17, 2026
0 Comments
Seeking Gaffer for Low Budget Dramedy Feature Film- I...
18/03/2026
COW Jobs: Seeking Location, Sound for Low Budget Dramedy - Chicago
Brie Clayton March 17, 2026
0 Comments
Seeking Location/Sound for Low Budget Dramed...
18/03/2026
COW Jobs: Seeking Child Wrangler for Low Budget Film - Chicago
Brie Clayton March 17, 2026
0 Comments
Seeking Child Wrangler for Low Budget Dramedy Fe...
18/03/2026
Calrec Redefines Broadcast Workflows at NAB 2026 with its Most Powerful Hardware...
18/03/2026
Oscar Nominated Two People Exchanging Saliva Posted with DaVinci Resolve Studio
Brie Clayton March 17, 2026
0 Comments
DaVinci Resolve Studio handle...
18/03/2026
Boston Conservatory Presents Celebrated Musical Satire Urinetown Performances for this Center Stage production will take place at Boston Conservatory Theater ...
18/03/2026
Charlie Puth Joins Switched On Pop at Berklee NYC The Berklee alum spoke with host and Berklee NYC professor Charlie Harding for a live taping, answering audi...
17/03/2026
NASA+'s Rebecca Sirmons and Brittany Brown offer unique look at live streami...
17/03/2026
The transition to IP has fundamentally reshaped professional media infrastructures. Video, audio, and increasingly metadata now circulate as independent, precis...
17/03/2026
Live sports streaming can push every element in your video delivery chain to its limit, exposing every potential weakness in seconds. When the Super Bowl, the O...
17/03/2026
Texas Athletics sought to modernize its media production, enhance fan experience...
17/03/2026
Ikegami USA will demonstrate the latest additions to its wide range of broadcast...
17/03/2026
TNA Wrestling and iHeartMedia announces a new multi-platform collaboration that will integrate iHeartMedia across TNA's premium live events, weekly televisi...
17/03/2026
The goal was to transform Hard Rock Stadium into a global leader in sports and e...
17/03/2026
Spectrum has announced the launch of its new Multiview feature in the Spectrum TV App, giving customers the ability to watch up to four NCAA men's or women&...
17/03/2026
Genius Sports deal also covers data technology, AI, fan engagement, and performance analysis....
17/03/2026
Net Insight is supporting the rollout of a new state-wide centralized operation with Rede Massa, which is an SBT affiliate, the Brazilian regional television ne...
17/03/2026
Featuring audio from practice sessions, qualifying races, and Grand Prix races, the film represents Apple's sports-media ambitions
At Sunday night's Ac...
17/03/2026
Live broadcast has always been one of the most demanding environments in media a...
17/03/2026
DirecTV is introducing several new viewing features, including a multi-screen March Madness Mix channel and an updated Sports Central mobile app hub, ahead of...
17/03/2026
Deltatre has announced a multi-year partnership with ATP Media, the media arm of the ATP Tour, covering broadcast graphics, data, and production across the 2026...
17/03/2026
The Detroit Pistons have announced a third consecutive season partnering with Sc...
17/03/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
17/03/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
17/03/2026
3D streaming infrastructure provider Miris today announced the launch of a public beta for its new 3D asset streaming platform. Miris is building the infrastruc...
17/03/2026
As media organizations face mounting pressure to produce more content, faster, while maximizing value and operational efficiency, Tedial, a leading provider of ...
17/03/2026
Brainstorm, a leading manufacturer of real-time graphics, augmented and virtual production, is launching the newest version of its platform, Brainstorm Suite 7,...
17/03/2026
Limecraft today announces the release of Limecraft 2026.2, the second platform update in its 2026 release cycle. Limecraft is an AI-powered production platform ...
17/03/2026
Broadcast Solutions, a leading system integrator and provider of innovative solutions for the broadcast and media industry, showcased its latest broadcast and V...
17/03/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
17/03/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
17/03/2026
QuickLink's Latest StudioEdge Models to Make North American Debut at NAB 202
Brie Clayton March 16, 2026
0 Comments
The Multi-platform Remote Gues...
17/03/2026
Frankenstein Graded with DaVinci Resolve Studio
Brie Clayton March 16, 2026
0 Comments
Sonnenfeld enhances the controlled interplay between warm and c...
17/03/2026
New Voyavox from Link Electronics with Real-Time Speech-to-Text Captioning to be...
17/03/2026
Berklee City Music Stewards META Fellowship Supporting Massachusetts Music Educa...