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
23/12/2025
How guilas Cibae as Dominican Winter League Games Are Locally Produced for Glob...
23/12/2025
BitFire's Jim Akimchuk on Supplying Scalability and Customization in the Clo...
23/12/2025
CAMB.AI Enables European Athletics to Offer Multi-Language SupportPlan is to eventually offer translation into all languages spoken in EuropeBy Ken Kerschbaumer...
23/12/2025
Analysis: As sports media values trend negative, scarcity and quality are king By Callum McCarthy, Editor-at-Large
Monday, December 22, 2025 - 14:08
Print ...
23/12/2025
ESPN, Disney, and NBA Return to the Animated Altcast Fray With Second Edition of...
23/12/2025
End the Year on a High Note and Donate to the Sports Broadcasting Fund Today! By Ken Kerschbaumer, Editorial Director
Tuesday, December 23, 2025 - 12:25 pm
...
23/12/2025
A Zeus motor is hot fire tested at L3Harris' Camden, Arkansas, solid rocket ...
23/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
23/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
23/12/2025
Lightware will exhibit several major product innovations at ISE 2026, including the new USB-C BOOSTER-V1, Google Meet. integration for various Taurus UCX models...
23/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
23/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
23/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
23/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
23/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
23/12/2025
Taking the Stage at Carnegie Hall-On a Global Scale Boston Conservatory Orchestra students reflect on their epic concert marking the 80th session of the UN Gene...
23/12/2025
Experience the power of WO Automation for Radio's newest service, the System Effectiveness Review. Designed to help you achieve more, a System Effectiveness...
23/12/2025
Back to All News
How Steamy Can It Get? Single's Inferno' Season 5 Pre...
23/12/2025
Back to All News
33 Million Global Viewers on Netflix Watched Jake Paul vs. Ant...
23/12/2025
New technique lights up where drugs go in the body, cell by cell Scripps Research scientists developed a technique that maps drug binding in individual cells th...
22/12/2025
SVG New Sponsor Spotlight: Presidio's Neerav Shah on the Role of Its Captiva...
22/12/2025
Hitting the bullseye: Sky Sports readies itself for the biggest PDC World Darts ...
22/12/2025
Unique skillset: Bringing new directors to the world of darts at The Worlds with...
22/12/2025
Gravity Media prepares for a flight of fancy with the PDC World Darts Championsh...
22/12/2025
One hundred and eighty: Gravity Media on hitting the production bullseye at the ...
22/12/2025
The Famous Group's Jon Slusser on Fascinating Fans Through Immersive Content...
22/12/2025
ESPN's Meg Aronowitz on Continuing High-Quality Broadcasts of Collegiate Spo...
22/12/2025
ESPN Takes Data-Driven Storytelling to New Heights with MNF Playbook with Next ...
22/12/2025
Paramount Scores Largest Share Increase Among Distributors as Paramount and CBS...
22/12/2025
New multi-year deal integrates Roku's data to fuel Nielsen's measurement suite
Roku gains access to Nielsen's streaming ratings, showing The Roku C...
22/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
22/12/2025
Berklee Wrapped 2025: Our Top News and Stories A look back at a year highlighted by faculty milestones, major film and television projects, Bob Dylan's ho...
22/12/2025
The works of Plato state that when humans have an experience, some level of change occurs in their brain, which is powered by memory - specifically long-term me...
22/12/2025
Workflows allow you to create a sequence of planned events which may be added to your template(s) or inserted directly into your sequential or background playli...
22/12/2025
Back to All News
Global Anime Hits and New Releases Take Center Stage at Jump Festa 2026
Entertainment
22 December 2025
GlobalJapan
Link copied to clipboar...
21/12/2025
Back to All News
Legoshi and Haru's Story Reaches Its Finale: BEASTARS Fin...
20/12/2025
Atomos announced the immediate availability of a new firmware update for its Ninja TX GO and Ninja TX monitor-recorders, unlocking ProRes RAW recording from the...
20/12/2025
CJP Broadcast has completed the digitisation of the European Gymnastics tape archive, converting 328 tapes containing more than forty years of recorded material...
20/12/2025
Bitmovin, the leading provider of video streaming solutions, today announced the launch of the Stream Lab MCP Server, to give AI agents and large language model...
20/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
20/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
20/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
20/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
20/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
20/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
20/12/2025
Barack Obama Includes Laufey on His 2025 Favorite Music List The former presidents roundup of books, music, and movies includes a song from the Berklee alums ...
20/12/2025
Study reveals a key hormonal circuit in the kidneys Scripps Research scientists identify the protein that helps kidney cells regulate renin, providing foundatio...
19/12/2025
SVG Sit-Down: Diversified's Jared Timmins on AI for Broadcast Sports and Cre...
19/12/2025
2025 SVG Summit Audio Recap: Say What?The Audio Production and Distribution Workshop at the SVG Summit 20 took on issues including speech intelligibility, Next-...
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
