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...
08/05/2026
For the second straight year, Miri Technologies Inc. has been honored with a pair of coveted awards at the broadcast, media and entertainment industry's pre...
08/05/2026
Nine Alumni Nominated for Tony Awards More than 20 alumni contributed to this year's Tony-nominated productions.
May 7, 2026
By
Tori Donahue
Boston Co...
08/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
08/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
08/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
08/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
08/05/2026
Liberty University on why broadcast technology isn't just a technical invest...
08/05/2026
COW Jobs: UGC, On-Camera Video Content
Brie Clayton May 7, 2026
0 Comments
UGC, On-Camera Video Content
April 17, 2026Documentary Editor - US,......
07/05/2026
Journalists reporting on Sudan are working in one of the most complex and fast-m...
07/05/2026
Multi-year partnership positions Victory+ as a free home for Dallas Cowboys orig...
07/05/2026
From sideline reporting to directing and producing, the talented sophomore is building a well-rounded foundation for a career in live sports production
In the ...
07/05/2026
Cobalt Digital has received two Future Best of Show awards at NAB Show 2026. The COBALT blueCORE platform was recognized by TV Tech, and the COBALT PACIFIC ULL-...
07/05/2026
ESPN analyst Mina Kimes will host the televised semifinals and finals of the 202...
07/05/2026
Bitmovin has announced that MUBI, the global film streaming platform, has selected Bitmovin as its cloud VOD encoding partner. Bitmovin's encoding infrastru...
07/05/2026
NBCUniversal Telemundo Enterprises and the U.S. Soccer Federation have announced...
07/05/2026
Angel City Football Club (ACFC) and Victory have announced a regional broadcast partnership bringing live match coverage to fans across the greater Los Angeles...
07/05/2026
Spiideo has announced the launch of AI Highlights inside Spiideo Play, its automated sports production platform. AI Highlights combines video, event data, audio...
07/05/2026
Leostream Corporation has announced a unified remote access ecosystem for high-p...
07/05/2026
The Atlanta Dream has partnered with Victory to stream all locally broadcast Dream games for free, expanding the team's digital distribution strategy and g...
07/05/2026
Riedel Communications has announced the appointment of Marc Engroff as Chief Fin...
07/05/2026
SES and ARD, Germany's largest public broadcasting network, have announced a long-term extension of their satellite distribution partnership through 2039. U...
07/05/2026
UpLight Technologies delivers a flexible video and lighting system for a new televised sportLaunching the Pro Cheer League required more than creating a compell...
07/05/2026
Full Day Productions and GSE Worldwide have announced Spikes Under the Lights, a...
07/05/2026
Seit dem Start im Jahr 2023 hat DJ (Beta) das personalisierte H rerlebnis von 94...
07/05/2026
Da quando stata presentata nel 2023, DJ (beta) ha aiutato a definire un'esperienza d'ascolto pi personalizzata per 94 milioni di utenti Spotify Premi...
07/05/2026
Since launching in 2023, DJ (beta) has helped shape a more personalized listenin...
07/05/2026
Desde o lan amento em 2023, o DJ (beta) j ajudou a deixar a experi ncia de ouvi...
07/05/2026
From our earliest days, Spotify has been built on a simple principle: Great audio should be easy to reach. It's what's driven us to expand from music to...
07/05/2026
Asian and Pacific Islander artists continue to shape the global soundscape, pushing creative boundaries and connecting with fans worldwide. This Asian & Pacific...
07/05/2026
Company announce long-requested choir instrument
In the latest expansion of their Symphonic Elements series, UJAM have introduced an all-new vocal instrumen...
07/05/2026
Modular-inspired sound generation with digital control
Buchla have introduced Ziggy, a new compact synthesizer built around the company's complex oscill...
07/05/2026
Combines analogue voices with digital synthesis and sequencing
Polyend have announced Drums, a new hybrid analogue and digital drum machine that combines sy...
07/05/2026
Control surface now officially supports four DAWs
When Nektar launched the Panorama CS12 control surface, it worked exclusively with Apple's Logic Pro, ...
07/05/2026
In the first quarter 2026, SGL Carbon generated consolidated sales of 184.5 million, which was 49.8 million, or 21.3%, lower than in the prior year (Q1 2025: ...
07/05/2026
Rohde & Schwarz and Greenerwave achieve precise and fast ESA antenna characteriz...
07/05/2026
Two multi-role L3Harris products - the Red Wolf launched effects vehicle and SK...
07/05/2026
L3Harris will be developing key features of a secure and resilient digital infra...
07/05/2026
Alysa Liu and Shohei Ohtani Help Drive Viewership as 91 of the Top 100 Broadcast...
07/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
07/05/2026
Cobalt Digital Wins Two Future Best of Show Awards at 2026 NAB Show
Manufacturer Recognized by TV Tech and TVBEurope for Innovation in signal processing
Cobal...
07/05/2026
Software and hardware platforms, AI power and user-friendliness on show...
07/05/2026
Intinor will demonstrate its latest technical enhancements for the Direkt series at BroadcastAsia 2026. With a continued focus on reliable contribution and remo...
07/05/2026
Bitmovin has announced that MUBI has chosen Bitmovin as its cloud VOD encoding partner, replacing MUBI's legacy on premises encoding setup to improve scalab...
07/05/2026
Meet Graduates from Berklees Class of 2026 Members of this years graduating class reflect on their proudest moments at Berklee and look ahead to whats next.
...
07/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
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.
