Sony Pixel Power calrec Sony

April 19, 2024

20/04/2024

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
LINK: https://www.scripps.edu/news-and-events/press-room/2024/20240419-yu-co...
See more stories from scripps

Most recent headlines

05/01/2027

Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be demoed at CES 2026

Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be ...

09/10/2026

Dolby Expands Dolby OptiView Platform with New Capabilities at IBC 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 Flex LTS Delivers Smarter Media Operations from Ingest to Distribution

Dalet, a leading technology and service provider for media-rich organizations, today announced the latest Long-Term Supported (LTS) release of Dalet Flex. Build...

22/09/2026

Young Journalist Award 2026: Meet the Final 12

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

ESPN, Precision Lasers Light Up NHL Player Media Tour in Las Vegas

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 Introduces KK 104 A and KK 105 A Wireless Capsule Heads

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

NFL and TMRW Sports Announce Pro Flag Showcase During Super Bowl LXI Week

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 Unveils New Daktronics Video Board and Audio System at Gesa Field

Washington State University has unveiled a new end zone video display and audio ...

22/09/2026

SVG Sit-Down: Disney's Dave Johnson on ESPN's New 4K HDR Distribution Pipeline and What It Means for Super Bowl LXI and Beyond

Disney's SVP of Live Operations and Engineering details the technology behin...

22/09/2026

Cosm Promotes Mazen Alawar to SVP of Marketing, Alexis Scalice to VP of Cosm Studios

Cosm has announced two senior promotions. Mazen Alawar has been promoted to SVP,...

22/09/2026

Mississippi State University Extends Camera Relationship with KOKUSAI DENKI

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 Appoints Christine Kjellvard as Interim CFO

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 Launches Zyntai TimeNode Access PTP Grandmaster for Edge Sites

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

The Weight Explores the High Cost of Freedom in the Depression Era

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

Avalanche Tones introduce Noise Suite

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...

22/09/2026

LW6 wireless headphones from Lewitt Audio

Uncompressed audio with below 6ms of latency Lewitt's have just introduced their first pair of headphones which, despite being aimed primarily at studio...

22/09/2026

Neumann launch the KK 104 A & KK 105 A

Two new capsule heads for Sennheiser wireless systems Neumann have announced the upcoming launch of the KK 104 A and KK 105 A, a pair of new premium condens...

22/09/2026

Apogee Plugins Are Moving to Plugin Alliance

Apogee Plugins Are Moving to Plugin Alliance We're excited to share an important update about the future of Apogee plugins. Apogee plugins are moving to Pl...

22/09/2026

SipRadius honored with a Technology And Engineering Emmy...

Parkland, Florida, US, September 22, 2026: SipRadius, widely recognized for making content processing and connectivity secure and seamless, has been honored wit...

22/09/2026

VanityFilter 3.1.5 adds project files and adjustable protection around lips, brows and ears

VanityFilter 3.1.5 adds project files and adjustable protection around lips, bro...

22/09/2026

Chile's TV+ Modernizes Broadcast Operations with Blackmagic Design

Chile's TV Modernizes Broadcast Operations with Blackmagic Design Brie Clayton September 22, 2026 0 Comments URSA Broadcast G2 brings versatility...

22/09/2026

OWC Shares Sneak Peek at Amazon Prime Big Deal Days Pricing

OWC Shares Sneak Peek at Amazon Prime Big Deal Days Pricing Brie Clayton September 22, 2026 0 Comments Image courtesy of Deposit Photos Business and ...

22/09/2026

Berklee's First Homecoming Block Party Brings Alumni Home for Global Music Festival

Berklee's First Homecoming Block Party Brings Alumni Home for Global Music F...

22/09/2026

New TVU Pocket Offers Broadcast Features In Phone-Sized Unit

Share Copy link Facebook X Linkedin Bluesky Email...

22/09/2026

Operative Launches Unified Platform for Advertising and Broadcast Management

Share Copy link Facebook X Linkedin Bluesky Email...

22/09/2026

Element Launches New TiVo-Powered Smart TVs in the U.S.

Share Copy link Facebook X Linkedin Bluesky Email...

22/09/2026

NOAA Taps Tomorrow.io for Improved U.S. Weather Forecasts

Share Copy link Facebook X Linkedin Bluesky Email...

22/09/2026

Gray Media Promotes Tim Maloney to GM and Director of Sales at WBKO

Share Copy link Facebook X Linkedin Bluesky Email...

22/09/2026

Reports: Paramount Reaches Settlement with State AGs in Antitrust Suit

Share Copy link Facebook X Linkedin Bluesky Email...

22/09/2026

New Research Lays Out Streaming Services Best Defense Against Churn

Share Copy link Facebook X Linkedin Bluesky Email...

22/09/2026

Sinclair Expands The National News Desk

Share Copy link Facebook X Linkedin Bluesky Email...

22/09/2026

Paramount Settles Antitrust Lawsuit over WBD Merger

Share Copy link Facebook X Linkedin Bluesky Email...

22/09/2026

U.S. Broadband Industry Investment Hits $92.6 Billion

Share Copy link Facebook X Linkedin Bluesky Email...

22/09/2026

Sky commissions Tupac murder trial documentary from Passion Pictures & Propagate Content

From Academy Award-winning Passion Pictures and BAFTA-winning director Marian Mo...

22/09/2026

Wi-Fi, phones and power lines: understanding EMF exposure

Whether it be from the sun or from our phones and other devices, we are all exposed to electromagnetic radiation in some shape or form. With the dramatic growth...

22/09/2026

Comscore's latest AI Intelligence Report Shows Competition Intensifying as Claude and Gemini Gain Ground on ChatGPT

Comscore's latest AI Intelligence Report Shows Competition Intensifying as C...

22/09/2026

The Factory-X Project Sets Standards for Data Sovereignty in Industry

The Factory-X Project Sets Standards for Data Sovereignty in Industry Arvato Systems Brings Digital Sovereignty to Industrial Practice Factory-X Successfully...

22/09/2026

Apple opens Apple Music Hall, a\u00A0state-of-the-art live music venue in London - PRESS RELEASE - Posted on 21 September 2026

LONDON Apple today announced the opening of Apple Music Hall, a brand-new state-...

22/09/2026

Young creativity across the island of Ireland takes centre stage as sixth RT This is Art! competition launches

RT , Creative Ireland and Shared Island Initiative ask young artists to respon...

22/09/2026

NVIDIA Isaac ROS 5.0 Advances Agentic, Open Source Robotics Development

To build and deploy sophisticated robotics applications that can perceive, reason and act in dynamic environments, developers need new physical AI models and to...

21/09/2026

Manifold Taps Ryhaan Williams for North America COO Post

Manifold Technologies, developer of software-defined, FPGA-accelerated infrastructure for live production, has named Ryhaan Williams as Chief Commercial Officer...

21/09/2026

SNS Wins IAMT Best Journal Article Award

Studio Network Solutions (SNS) has won Best Journal Article at the 2026 IAMT Impact Awards for What Video Editors Need When Everything Is Changing Around Them,...

21/09/2026

MLW Announces Streaming Deal with Tubi for Weekly FUSION Series

Major League Wrestling (MLW) has announced a streaming distribution agreement with Tubi for its weekly series MLW FUSION. Beginning September 17, new episodes w...

21/09/2026

Adam Smith Named Chairman of Direct-to-Consumer at Disney Entertainment

Disney Entertainment has announced that Adam Smith has been named Chairman, Direct-to-Consumer, with responsibility for Disney and Hulu including product, engi...

21/09/2026

United Airlines and DISH to Offer Live Football on Starlink-Enabled Seatback Screens

United Airlines and DISH have announced an agreement to bring live professional ...

21/09/2026

SES to Provide Satellite Distribution for JioStar Channels Across India

SES and JioStar have announced a multi-year agreement under which SES will provide satellite distribution services for JioStar's television channel portfoli...

21/09/2026

Detroit Red Wings Announce Detroit SportsNet Broadcast Details for 2026-27 Season

The Detroit Red Wings have announced details for their inaugural season on Detro...

21/09/2026

Manifold Technologies Appoints Ryhaan Williams as CCO for North America

Manifold Technologies has appointed Ryhaan Williams as Chief Commercial Officer for North America, effective October 1, 2026. Based in Jacksonville, Florida, Wi...

21/09/2026

DAZN Pick Up L.A. Kings DTC Streaming Rights; ABTV Will Continue as Local TV Home

Angels Broadcast Television (ABTV), the local television home of the Los Angeles...