Crossing the ring: new method enables C-H activation across saturated carbocycles Scripps Research chemists add another powerful tool to their molecular editing toolkit for crafting pharmaceuticals and other valuable compounds.
May 31, 2023
LA JOLLA, CA A new molecular editing technique from Scripps Research enables chemists to add new elements to organic molecules at locations that were previously out of reach.
The researchers described their new method in a paper that appeared on May 31, 2023, in Nature. The method uses a designer molecule called a ligand that helps a palladium-atom catalyst reach from one side of a carbon-atom ring to break a carbon-hydrogen bond on the other side, allowing a new set of molecules to join at that site. This molecule-building feat was previously impossible for so-called saturated rings of carbon atoms, which are common features in drug molecules.
Previously, to achieve the same result, one would have to undertake a de novo approach what we call a cyclization reaction involving the formation of a new ring structure from an acyclic chain, using this new method, we can directly modify an existing ring to avoid a cyclization process that can often prove challenging, says study senior author Jin-Quan Yu, PhD, the Bristol Myers Squibb Endowed Chair in Chemistry and the Frank and Bertha Hupp Professor in the Department of Chemistry at Scripps Research. In addition to saving steps, this unprecedented synthetic strategy can introduce new chemical space for drug discovery as structurally distinct substrates are incorporated into the ring.
Yu and his laboratory are already renowned for their innovations in C-H functionalization, which is a powerful way of building complex organic molecules to make new pharmaceuticals and other valuable commercial compounds. In this approach, chemists use ligands and catalysts to disconnect a hydrogen (H) atom from a carbon (C) atom at a desired position on an organic molecule. This disconnection allows a new cluster of molecules, known as a functional group, to bond where the hydrogen atom had been.
Most molecules that are used to build new drugs include rings of carbon atoms, also called carbocycles. Thanks in part to Yu's group, the C-H functionalizations of carbon atoms on these rings have become relatively easy in many cases. This approach is often not applicable, though, in cases where the existing functional group needed to anchor the ligand and catalyst is directly across the ring from the desired C-H functionalization site.
We call this scenario crossing the river,' and it has been extremely challenging because the palladium catalyst must form a strained bridge' connecting the existing functional group and the desired carbon site on the other side of the ring, Yu says.
The most challenging cases are those in which the carbon-ring structures are saturated, which means their carbons are connected only with single carbon-carbon bonds. Saturated carbon rings are common in pharmaceutical chemistry, but are harder targets for C-H functionalization, in part because the C-H bonds have less affinity for metal catalysts, compared to the double C-C bonds of unsaturated carbon rings. The Yu lab has achieved C-H functionalization across unsaturated rings, but there has been no way to do this across a saturated ring until now.
In the study, Yu and his team, including co-first authors Guowei Kang, PhD, Daniel Strassfeld, PhD, and Tao Sheng, PhD, all postdoctoral research associates in the Yu lab, were able after months of trial and error to develop quinuclidine-pyridone and sulfonamide-pyridone ligands enabling cross-ring functionalization with saturated carbon rings. They showed that the approach can work for rings containing from four to eight carbon atoms, within a wide variety of molecules.
The researchers demonstrated the new technique by easily functionalizing molecules that are being used to develop future drugs, including compounds called histone deacetylase inhibitors, which are under investigation as potential cancer treatments.
We anticipate that this new tool will greatly simplify the synthesis of a large class of carbocyclic molecules used in pharmaceutical chemistry, expanding chemical space for the discovery of new and better drugs, Yu says.
Transannular C H Functionalization of Cycloalkane Carboxylic Acids was co-authored by Guowei Kang, Daniel Strassfeld, Tao Sheng, Chia-Yu Chen and Jin-Quan Yu, all of Scripps Research.
The research was supported by grants from the National Institute of General Medical Sciences (2R01GM084019 and F32GM143921).
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 ...
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...
04/07/2026
April 7 2026, 19:00 (PDT) Detective Conan: Fallen Angel of the Highway Opens in...
01/07/2026
Broadcast Management Group (BMG) has announced the appointment of Kathy Samuels ...
01/07/2026
Shade has announced Custom Objects and Automations, a platform expansion releasing June 29, 2026, that adds database and workflow automation capabilities direct...
01/07/2026
FOR-A America has announced the addition of Jaz Wray and Fernando Cruz to its U.S. sales team. Both report to Ernie Leon, Senior VP and Head of Sales and Strate...
01/07/2026
NBC Sports will air all 15 MLB games nationally on Sunday, July 5, across NBC, P...
01/07/2026
Clear-Com has announced a wireless communications upgrade for Jeopardy! and Wheel of Fortune, deploying FreeSpeak II and FreeSpeak Icon systems across both prod...
01/07/2026
England's performance team will use Sony's STATSports APEX GPS tracking system to monitor player physical data in real time during FIFA World Cup 2026 m...
01/07/2026
Adder Technology has announced the appointment of Neil Hillier as Chief Executive Officer, effective July 1, 2026. Hillier succeeds Adrian Dickens, who transiti...
01/07/2026
Bitcentral, Inc. has announced a strategic transaction creating two separate companies. The Production and Playout business will continue as Bitcentral, now own...
01/07/2026
DAZN has announced results from DAZN48, its creator initiative for the FIFA World Cup 2026. Launched in April 2026, the program received thousands of applicatio...
01/07/2026
Sarah Rose, VP, global services, Daktronics (NASDAQ: DAKT), will be inducted into the Information Display and Entertainment Association (IDEA) Hall of Fame at t...
01/07/2026
Gravity Media and the World Economic Forum's production team provided broadc...
01/07/2026
Insight Productions has announced the launch of Insight Storm, a 53-foot mobile broadcast unit built for esports production. The truck is built around a Ross Vi...
01/07/2026
ESPN has announced several content initiatives marking America's 250th anniversary, as part of The Walt Disney Company's Disney Celebrates America pro...
01/07/2026
Eleven production kits, REMI workflows, and cloud distribution bring 40 World Cu...
01/07/2026
The conference also discussed the opportunities offered an industry that is endu...
01/07/2026
The Mountain West Conference has announced the launch of MW , a direct-to-consumer streaming platform powered by Kiswe. The platform will carry live Mountain We...
01/07/2026
New AI Assistant, Multi-channel Audio, ARA2 improvements & more
Tracktion's DAW software has just received its latest major update, gaining a selection ...
01/07/2026
Stammering, stuttering, strangulated tones
The Crow Hill Company's latest creation promises to be the most original sound set they've produced to d...
01/07/2026
Exclusive run of limited-edition modelling pedals
Sweetwater and Andertons M...
01/07/2026
The National Film and Video Foundation (NFVF) is pleased to announce that the ca...
01/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/07/2026
Manfrotto Introduces UNCOVER, the new premium camera bag collection for modern h...
01/07/2026
Blackmagic Design Powers Houston Tamil Sangam Literacy Competition
Brie Clayton July 1, 2026
0 Comments
Volunteers use ATEM Mini Pro, Blackmagic Desig...
01/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/07/2026
PlayBox Technology has published State of Broadcast Infrastructure 2026, an in-depth industry research report examining the technologies, operational challenges...
01/07/2026
LONDON, UK, 1 JULY Jigsaw24 has appointed Alan Henry as Head of Sales for Media and Entertainment, reinforcing its continued investment in helping broadcaster...
01/07/2026
Content Vault, the patent-pending secure content distribution platform protecting high-value media from disclosures, theft and unauthorised access, today announ...
01/07/2026
Bitcentral, Inc. a leading provider of enterprise software and digital media solutions for news, sports and entertainment broadcasters, as well as streaming pla...
01/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/07/2026
Groundbreaking First Nations Screen Business Accelerator launched through nation...
01/07/2026
Chyron Launches the All-New Chyron Academy: A Reimagined, Hands-On Learning Expe...
01/07/2026
Amplium Captures Kawasaki Brave Thunders Game with Blackmagic URSA Cine Immersiv...
01/07/2026
Boris FX Optics Expands Plugin Support to Apple Photos, Capture One, and Affinit...
01/07/2026
UKTV has today announced the appointment of Matt Berry to the newly created role of General Manager - Marketing, effective 1 July.
Matt will take on this senio...
01/07/2026
Sky Zero Footprint Fund-backed TV campaign featuring Deborah Meaden challenges consumers to rethink everyday bathroom wasteWednesday 1 July 2026
Fussy asks Bri...
01/07/2026
Constituency-level analysis reveals where girls miss out most on sport - and where targeted action could unlock more than £640 million in economic and health be...
01/07/2026
Wuppertal July 1, 2026
Riedel and SKAARHOJ Expand Collaboration With SimplyLive IntegrationRiedel Communications today announced an expanded collaboration wit...
01/07/2026
Apple today introduced power-packed updates to Apple Creator Studio, a groundbre...
Crossing the ring: new method enables C-H activation across saturated carbocycles Scripps Research chemists add another powerful tool to their molecular editing toolkit for crafting pharmaceuticals and other valuable compounds.
