
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
Most recent headlines
05/01/2027
Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be ...
09/10/2026
September 10 2026, 06:00 (PDT) Dolby Expands Dolby OptiView Platform with New Capabilities at IBC 2026
New Sports Intelligence helps providers better unders...
07/10/2026
Dalet, a leading technology and service provider for media-rich organizations, today announced the latest Long-Term Supported (LTS) release of Dalet Flex. Build...
23/09/2026
Four control rooms support B1G+ streams, videoboard shows, creative content, and...
23/09/2026
By Andrew Cohen, SVG Coorespondant
The Mountain West debuted its new Replay Operations Center at the start of this football season, bringing real-time collabor...
23/09/2026
The Taylorville, IL, native is pushing creative boundaries at Ball State, gaining reps across directing, technical directing, tape, and more than 100 ESPN+ broa...
23/09/2026
Alexander Heller, Nevada Jose, Will Brill, and Giselle Bonilla pose with cast members at The Musical premiere during the 2026 Sundance Film Festival at Eccles...
23/09/2026
Includes natural and processed patches
The Crow Hill Company's latest sample library captures a children's choir comprising a troupe of boys perform...
23/09/2026
Plug-in offers six bands of saturation
Kreuzberg Audio's product range includes a selection of plug-ins and virtual instruments aimed primarily at hard-...
23/09/2026
Latest DAW update now live
SoundBridge have announced that the latest update for the remote-collaboration-focused DAW is now available. The release of Sound...
23/09/2026
Koori Knockout returns home exclusively to NITV and SBS On Demand in 2026
11 September, 2026
Media releases
Fans can catch all the live action exclusively ...
23/09/2026
Rohde & Schwarz acquires NEOSAT and PHYTRONIC and strengthens its competencies i...
23/09/2026
1. ABOUT THE PROGRAMME
The National Film and Video Foundation (NFVF) invites applications from experienced producers who own or manage a South African product...
23/09/2026
The National Film and Video Foundation (NFVF) is pleased to announce the opening...
23/09/2026
Download Now!
To receive a short case study showcasing NHK Technologies, Inc. (NT) s audio setup, please enter the following details:
--
First Name* Fir...
23/09/2026
Nielsen CMI data reveals a changing fast-food landscape, with value, convenience...
23/09/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
23/09/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
23/09/2026
COW Jobs: Blender on Windows - Generalist - Remote
Brie Clayton September 23, 2026
0 Comments
Application Users - Blender on Windows - Generalist
Se...
23/09/2026
Version 1.8 recognised for new workflow tools, boosted control panel flexibility and ease of integration into IP networks...
23/09/2026
Hiltron Communications reports a successful 2026 International Broadcasting Convention, held at the RAI Amsterdam. Exhibiting on stand A37 in Hall 1, Hiltron ex...
23/09/2026
Reinforcing its long-term commitment to the Middle East and North Africa (MENA) broadcast market, LiveU is presenting the Q Era at CABSAT 2026, on Stand H1-D35 ...
23/09/2026
Agence France-Presse (AFP), a global news agency, and Dalet, a leading technology and service provider for media-rich organizations, today announced a partnersh...
23/09/2026
Berklee Connect Unlocks the Power of a Global Network Katie Vitolins BM '04 knows firsthand what Berklee's alumni community can make possible. Now she...
23/09/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
23/09/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
23/09/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
23/09/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
23/09/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
23/09/2026
Westminster Schools, a K through 12 school in Atlanta, Georgia with approximately 2,000 students, has transformed its student broadcast and digital storytelling...
23/09/2026
The 2026 edition of CABSAT and SATExpo may have a new home and dates in the diary, but it still retains a strong presence from UK companies in the GREAT Britain...
23/09/2026
Glensound will return to CABSAT with new developments in professional monitoring and Dante interfacing, alongside its established commentary, esports and parlia...
23/09/2026
Wednesday 23 September 2026
Sky Sports to show England Men's tour of South ...
23/09/2026
Comscore Partners with datafuelX to Bring Seamless Currency Adoption Into a Comp...
23/09/2026
Luxembourg, 23 September 2026 - SES today announced the appointment of Mr. Michel Scholer, Secretary General of the Luxembourg Government and Chief of Staff to ...
23/09/2026
RT One and RT Player, Friday 25 September
Ceol le Ch ile, a new series that follows Irish artists as they collaborate with musicians from diverse background...
23/09/2026
Available now on RT Listen
New information has come to light in the case of mi...
23/09/2026
When Sakeena Fiza describes her work as a validation engineer at NVIDIA, she does so in terms more befitting a detective story than a world-class engineering la...
22/09/2026
From Malaysia to Mexico and from DR Congo to Ukraine, this year's 12 finalists for the 2026 Thomson Foundation Young Journalist of the Year award tell extra...
22/09/2026
The annual preseason content-gathering event brought 36 NHL players to Las Vegas, where ESPN used 2.5 kilowatts of laser power and a motion-control camera syste...
22/09/2026
Neumann has introduced the KK 104 A (cardioid) and KK 105 A (supercardioid) wireless capsule heads, succeeding the KK 204 and KK 205. The new capsules are compa...
22/09/2026
The NFL and TMRW Sports have announced a new annual Pro Flag Showcase to be held during Super Bowl LXI week in Los Angeles. The event will feature top flag foot...
22/09/2026
Washington State University has unveiled a new end zone video display and audio ...
22/09/2026
Disney's SVP of Live Operations and Engineering details the technology behin...
22/09/2026
Cosm has announced two senior promotions. Mazen Alawar has been promoted to SVP,...
22/09/2026
Mississippi State University's University Television Center has purchased four KOKUSAI DENKI SK-UHD7000-S2 cameras since 2024, with plans to add two more, a...
22/09/2026
Net Insight has announced that Christine Kjellvard will assume the role of interim Chief Financial Officer on November 1, 2026. Kjellvard has previously held in...
22/09/2026
Net Insight has announced Zyntai TimeNode Access, a compact PTP Grandmaster designed for distributed edge sites. The product carries secure, precise time across...
22/09/2026
Sam Hazeldine, Austin Amelio, Padraic McKinley, Julia Jones, and Ethan Hawke attend the premiere of The Weight at The Ray Theatre on January 26, 2026, in Park...
22/09/2026
Second high-gain tone plug-in released
Following on from their debut release, Chainsaw Suite, Avalanche Tones have announced the launch of their second plug...