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 ...
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...
06/09/2026
June 9 2026, 23:00 (PDT) Dolby and MagentaTV Bring Fans Closer to the FIFA Worl...
04/08/2026
Dalet, a leading technology and service provider for media-rich organizations, t...
15/07/2026
The 2026 FIFA World Cup is a big deal for DAZN, which has distribution rights in three markets: Italy, Spain, and Japan. Each requires a different editorial app...
15/07/2026
As sports-media organizations manage rapidly growing content libraries and incre...
15/07/2026
HBS director of digital Johannes Franken talks SVG Europe through the operation built to serve FIFA World Cup 2026 rights holders remotely from Stratford, east ...
15/07/2026
IBC has unveiled the conference program for IBC2026, with this year's event ...
15/07/2026
Software-defined wideband RF platform supports 96-kHz monitoring, streamlined fr...
15/07/2026
New AI-powered module enables broadcasters and content owners to extract dialogu...
15/07/2026
Weeklong gathering at EBU headquarters will test new IPMX capabilities and expand certified product ecosystem...
15/07/2026
Force Tech has announced the appointment of Bryan Adams, CTS, as Vice President of Integration. Adams will oversee AV and broadcast integration project delivery...
15/07/2026
USA Sports has announced an exclusive English-language agreement with the Bundes...
15/07/2026
ITV Sport's FIFA World Cup 2026 coverage has been produced from one of the m...
15/07/2026
Program will provide professional camera kits, training, and technical support to participating local newsrooms...
15/07/2026
San Francisco church becomes first U.S. deployment of the 2 M/E production switcher...
15/07/2026
Former ESPN and NFL Network executive to advise startup league on media, distribution, technology, and fan engagement...
15/07/2026
The Houston-based RSN is the live-game home of the Astros and Rockets...
15/07/2026
Launched alongside new FreqSoft installer
Designed to bridge the gap between hardware and software, Freqport's FreqInOut FO1 unit provides a simple way ...
15/07/2026
Save up to 55% on software until 23 July 2026
Expressive E have just launched their Summer Offer sale, with discounts of up to 55% now applied across their ...
15/07/2026
Real-time stem-separation tool updated
zplane have recently released a new and improved version of their real-time stem-separation plug-in which they say ma...
15/07/2026
A new benchmark in bass enhancement
Described as a new benchmark in bass enhancement , Baby Audio's latest release has been designed to augment the lo...
15/07/2026
DMC Production's AR 1 and AR 2 units reverse the conventional OB workflow, keeping all production-critical processing at the venue while operators work remo...
15/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
15/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
15/07/2026
GigaCloud, a leading Ukrainian cloud service provider, and Cubbit, the first geo-distributed cloud storage enabler, today announced a new Business Alliance Part...
15/07/2026
SMPTE, the global society for media professionals, technologists, and engineers, has announced the launch of the SMPTE 110th Anniversary Campaign, a fundraising...
15/07/2026
Studio Technologies, a leading manufacturer of high-quality audio, video, and fiber-optic solutions, unveils the new StudioComm Model 762 Stereo Level Control, ...
15/07/2026
COW Jobs: Producer, Virtual Events - Hybrid, Full Time, Salaried
Brie Clayton July 15, 2026
0 Comments
Producer, Virtual Events (Hybrid | Full-time | ...
15/07/2026
Brazilian media organization builds nationwide CDN with Broadpeak's high-performance software for low-latency streaming and new content distribution service...
15/07/2026
DHD announces a new utility designed to increase the efficiency of its audio mixing systems during initial installation and subsequent configuration.
Anyone w...
15/07/2026
BCNEXXT Brings Next-Generation Vipe to IBC2026, Breaking the 1:1 Channel-to-Server Ratio New innovations liberate broadcasters from legacy playout infrastructur...
15/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
15/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
15/07/2026
Wednesday 15 July 2026
Screeners and press pack now available: Gomorrah: The Or...
15/07/2026
Trinity's Treasures features Ruth Negga, Eleanor McEvoy, and David Norris, a...
15/07/2026
Join geographer Dr Susan Hegarty, Engineer Tim Joyce and Architect Orla Murphy a...
15/07/2026
Home to leading manufacturers, robotics pioneers, infrastructure builders and gaming, of course, Japan is one of the world's centers of AI - building across...
14/07/2026
South end zone videoboard, cloud-based control system will be ready for 2026 football season...
14/07/2026
Redesigned website, enhanced mobile app unify content, ticketing, and personalized fan engagement...
14/07/2026
Agreement spans sponsorship sales, digital monetization, radio production, and new practice facility naming rights...
14/07/2026
Independent league adds 14 regional sports network affiliates, growing distribut...
14/07/2026
New strategy aims to unify competitions, content, fan engagement, and commercial...
14/07/2026
ESPN and Disney+ become exclusive home of PFL events in key international MMA market...
14/07/2026
Gill will oversee engineering, technology, and sports operations across the company's 64 local television stations...
14/07/2026
Submitted by North American Broadcasters Association (NABA)
As broadcasters con...
14/07/2026
Modernized mobile unit combines HOME Apps, mc 56 console, and IP infrastructure ...
14/07/2026
Every match of the 32-team tournament will air across ION and Scripps Sports platforms in English and Spanish...
14/07/2026
FloHockey to stream every game of the annual international tournament under four...
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
