Scripps Research chemists develop new method for making gamma chiral centers on simple carboxylic acids C-H activation-based method should speed drug molecule design and diversification.
May 17, 2024
LA JOLLA, CA Scripps Research chemists have accomplished a long elusive feat in synthetic chemistry: the invention of a broadly useful method for constructing gamma chiral centers on simple starting compounds called carboxylic acids. The method, published on May 16, 2024 in Science, significantly extends the ability of chemists to build and modify complex pharmaceutical molecules and other valuable chemical products.
The term chiral refers to a type of asymmetry that allows some chemical compounds to exist in left-handed and right-handed forms. Often, only one of these forms has the desired biochemical activity, but for synthetic chemists, stereoselective reactions those that yield just the desired form are almost always challenging.
The new method enables what had been impossible except in narrow cases: creating a center of chiral asymmetry at a hard-to-reach position called the gamma position on a cyclic carboxylic acid.
This approach offers unprecedented and relatively easy access to a broad set of chiral carbocycles that are privileged structures for pharma industry drug discovery programs, 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 co-first authors were Tao Zhang, PhD, and Zi-Yu Zhang, PhD, both postdoctoral research associates in the Yu lab.
A potentially valuable but elusive method
The development of small molecule pharmaceuticals or other chemical products typically involves the construction of many hundreds or thousands of compounds, each representing a variation on a central structural theme. Once these libraries of compounds are constructed, they are methodically tested for the desired biological or chemical activity; in this way, developers can zero in on the best compound for further refinement. Naturally, in constructing these libraries and in making more refined variants, chemists would like to have easy and versatile techniques for building and modifying molecules. But while their tools have greatly improved over the years, some types of molecular transformation have remained essentially undoable, despite the obvious value they would have. Gamma chiral center construction using readily available carboxylic acids has been one of these, defying the efforts of prominent synthetic chemistry labs.
The Yu lab's success hinged on the development of special ligand molecules containing both oxazoline and pyridone structural elements. Ligand molecules help bring the reaction catalyst to the right spot on the initial compound. In this case, they fasten to one point on the starting carboxylic acid which contains a ring of mostly carbon atoms and direct a bond-breaking palladium atom to the distant gamma position on the other side of the ring. The effect is to remove a hydrogen atom from the backbone carbon atom at the targeted spot, allowing a new cluster of atoms to bond to the carbon thus adding complexity to the molecule in a precise way.
This type of reaction is called a C-H activation, and over the past decade, Yu and his team have reported similar C-H activation methods for constructing chiral centers at alpha and beta positions on carboxylic acids.
The chemists demonstrated the power and versatility of their new method by using it to make gamma chiral centers on a wide variety of relatively simple carboxylic acid starting compounds containing rings of from five to eight carbon atoms. In one case, they achieved a single-step synthesis of a chiral version of a cancer drug molecule called an HDAC inhibitor whose standard, patented synthesis method requires 10 steps and a costly separation to obtain pure samples of the left-handed or right-handed form.
The team also used the new technique to add complexity to existing drug molecules, including the steroid hormone pregnenolone.
Finally, the chemists showed they could use their new approach sequentially on a starting molecule to construct three chiral centers including a very challenging delta chiral center.
The Yu lab is now working to extend the new approach so it can be used for making other types of chiral molecules.
Enantioselective Remote Methylene C H (Hetero)Arylation of Cycloalkane Carboxylic Acids was co-authored by Tao Zhang, Zi-Yu Zhang, Guowei Kang, Tao Sheng, Jie-Lun Yan, Yuan-Bin Yang, Yuxin Ouyang and Jin-Quan Yu, all of Scripps Research.
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 ...
04/08/2026
Dalet, a leading technology and service provider for media-rich organizations, t...
04/07/2026
April 7 2026, 19:00 (PDT) Detective Conan: Fallen Angel of the Highway Opens in...
01/06/2026
January 6 2026, 05:30 (PST) Dolby Sets the New Standard for Premium Entertainment at CES 2026
Throughout the week, Dolby brings to life the latest innovatio...
12/05/2026
Beyond the Hype: A Strategic Post-Hoc Analysis of NAB 2026 If NAB Show 2026 had an underlying theme, it was a quiet, industry-wide pivot from the high-energy sp...
12/05/2026
Guntermann and Drunck (G&D), a Panoptec Technologies Group company, and CT Square, led by Chandresh Shah, have announced a joint venture to distribute G&D and V...
12/05/2026
With 30 days until the start of the FIFA World Cup 2026, Telemundo, the exclusive Spanish-language home of the tournament in the United States, has announced th...
12/05/2026
The NHL has announced the return of Stanley Pup for its third consecutive year, a 90-minute special featuring adoptable rescue dogs competing on a miniature rin...
12/05/2026
NBCUniversal presented its 2026 Upfront to advertisers at Radio City Music Hall, detailing upcoming programming across NBC, Peacock, Bravo, and Versant properti...
12/05/2026
FOX Sports has announced funding for the Fandom and Social Connection Initiative at Harvard Kennedy School's Shorenstein Center on Media, Politics, and Publ...
12/05/2026
TNDV and Live Media, both divisions of Live Media Group, supported live broadcast coverage around NCAA Final Four weekend in Indianapolis, including the March M...
12/05/2026
The European Football Alliance (EFA) has announced a content distribution agreement with Fubo Sports Network, the free ad-supported streaming TV (FAST) channel ...
12/05/2026
For the first time, Spanish-speaking fans in the U.S. will have two separate tel...
12/05/2026
CP Communications led a comprehensive spectrum management initiative on behalf of Churchill Downs during Kentucky Derby week, coordinating RF assets across the ...
12/05/2026
LiveU has announced a strategic partnership with DRONERESPONDERS, a 501(c)3 non-...
12/05/2026
Open Broadcast Systems has announced that BMC TV, a specialist in IP transport of broadcast content, has selected the Open Broadcast Systems 5G Flyaway solution...
12/05/2026
NEP Europe, part of NEP Group, has announced it will deliver broadcast solutions...
12/05/2026
Grass Valley has announced continued collaboration with Ravensbourne University ...
12/05/2026
Stats Perform has announced the launch of Opta Pulse, an AI-assisted video creation and distribution platform for leagues, rights holders, and broadcasters. The...
12/05/2026
FOX Sports has announced a collaboration with Sesame Workshop to integrate Sesame Street characters into FOX Sports' FIFA World Cup 2026 programming. Conten...
12/05/2026
To date, NHL Productions has produced 19 broadcasts with commentary in American Sign Language
NHL in ASL (American Sign Language) may be just one show, but the...
12/05/2026
Google's Brian Albert: creators, athletes, highlights, nostalgia, second-scr...
12/05/2026
A still from Past Lives by Celine Song, an official selection of the Premieres program at the 2023 Sundance Film Festival. (Courtesy of Sundance Institute | p...
12/05/2026
Spotify is where fans and artists come together, turning discovery into somethin...
12/05/2026
Features patented Marco-MMC clocking technology
Black Lion Audio's latest release combines the company's expertise in clocking with their renowned p...
12/05/2026
New Track Panel, sequencer upgrades & more
Following their recent public beta release, Reason Studios have announced the full release of Reason 14. With the...
12/05/2026
One month to go! SBS reveals expansive FIFA World Cup 2026 lineup beyond the pi...
12/05/2026
Rohde & Schwarz presents its advanced solutions for power electronics testing at...
12/05/2026
aconnic AG (ISIN: DE000A0LBKW6), Munich, has developed a modified fund raising p...
12/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
12/05/2026
Tyrell Corporation, specialists in high-end live sports and entertainment broadcasts, was tasked with delivering compelling broadcast coverage of premier equest...
12/05/2026
Registration is now open for IBC2026 as the global media, entertainment and technology community prepares to converge on the RAI Amsterdam from 11 14 September ...
12/05/2026
Ross Video, a global leader in live video production technology, will present its latest innovations and integrated production workflows at BroadcastAsia 2026, ...
12/05/2026
500 selected leaders from around the world across start-ups, corporates, and venture capital. Over 50bn in assets under management among attending investors, a...
12/05/2026
CVP, one of Europe's leading suppliers of professional video and broadcast solutions, has appointed Randy Koeman as Sales Manager, Netherlands, marking anot...
12/05/2026
Taiwan Television has expanded its HD content ingest workflow capabilities by investing in the PlayBox Neo Suite - a leading multi-channel multi-server UHD/HD/S...
12/05/2026
Jigsaw24 is strengthening its media team with the appointment of Tom Laker as Client Director and Ashish Chauhan as Project Manager. These strategic hires bring...
12/05/2026
Broadcast playout leader showcases hybrid IP infrastructure and workflow automation with Videoland deployment as regional benchmark...
12/05/2026
dzjinius, the all-in-one production management platform for the media and entertainment industry, will showcase its centralised approach to production workflows...
12/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
12/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
12/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
12/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
12/05/2026
NUGEN Audio will debut Version 1.1 of DialogCheck, its intelligent dialog intelligibility and compliance tool, at the 2026 Media Production & Technology Show (S...
12/05/2026
The reactive visuals can adapt to any stage or screen setup and comprise 50 layers of Notch content
Today, Disguise announced that its high performance GX 3 m...
12/05/2026
Snapgrid , Snapbag & Airglow Expand Creative Control for the ARRI Modular LED BarFollowing the launch of the ARRI Omnibar, DoPchoice introduces a dedicated li...
12/05/2026
May 12th, 2026 Press Materials Available Here
TRIBECA FESTIVAL UNVEILS 2026 GAMES PROGRAM
Tribeca Celebrates Its 25th Anniversary With World Premieres and Pl...
12/05/2026
May 12th, 2026 Press Materials Available Here
MADONNA BRINGS THE WORLD PREMIERE OF CONFESSIONS II TO 2026 TRIBECA FESTIVAL
The Global Icon Will Unveil a Cine...
12/05/2026
Customer demand for data continues to grow in the first quarter of 2026 at Magya...
Scripps Research chemists develop new method for making gamma chiral centers on simple carboxylic acids C-H activation-based method should speed drug molecule design and diversification.
