The new method allows easy and versatile synthesis o

LA JOLLA, Calif.—Scripps Research chemists have unveiled a method to turn cheap and widely available chemicals known as dicarboxylic acids into potentially very valuable molecules called lactones.

Lactone structures are common in biologically active natural molecules; they are found, for example, in vitamin C and in erythromycin, an antibiotic of bacterial origin. Techniques for synthesizing lactones have long been available to chemists, but these techniques are quite limited in what they can produce. The achievement, reported on May 26, 2022, in Sciencemakes building diverse and complex lactones easier than ever.

“This method should be very widely useful for developing new pharmaceuticals, polymeric materials, perfumes and many other chemicals. We are already receiving inquiries from interested manufacturers,” says Jin-Quan Yu, PhD, Frank and Bertha Hupp Professor of Chemistry. at Scripps Research.

Yu and his lab are renowned for their innovations in building molecules, especially with regard to “CH activation”. It involves the use of specially designed catalyst molecules to remove a hydrogen (H) atom from a carbon (C) atom on an organic molecule and to replace the hydrogen atom with a group of atoms more complex.

The overall goal is to develop a set of methods to perform CH activation selectively on any chosen carbon atom on a starting molecule – and the dream is to use these methods to transform cheap molecules and relatively simple drugs, plastics and other complex and valuable molecules. .

In this case, Yu and his team aimed to perform particularly difficult and selective CH activations to convert cheap and readily available dicarboxylic acids into high-value lactones. Dicarboxylic acids, despite their seemingly complicated name, are relatively simple molecules and are ideal starting materials for many types of chemical synthesis. But chemists attempting CH activation of dicarboxylic acids have always faced considerable obstacles.

“CH activations at sites of a dicarboxylic acid distant from one of its carboxyl groups have been very difficult to date,” says Yu. by controlling the catalyst, seemed like an impossible dream.”

The feat achieved by Yu and his team, including first author Sam Chan, PhD, a Croucher Foundation postdoctoral fellow in the Yu lab, was a set of methods using palladium-based catalysts to freely obtain CH activations on of reaching carbons on a dicarboxylic acid.

“Over the past two decades, we have succeeded in developing good methods for activating the two-carbon CH of a carboxyl, but now, with our new methods, we can also achieve one more carbon, and with the freedom to choose between the two sites, we can easily access a new chemical space in drug discovery,” Yu says. essentially with this approach, one can construct a very wide range of complex lactone compounds.”

Yu and his team demonstrated the ease and utility of their new methods by synthesizing – from cheap dicarboxylic acids – two complex natural lactones, a fungal molecule called myrotheciumone A, which has been studied for anti-cancer properties, and the pedicellosin vegetable lactone.

Chemists are now using the new methods to generate hundreds of diverse lactone structures, whose properties and potential to develop into future pharmaceuticals they are exploring in collaboration with the lab of Ben Cravatt, PhD, Gilula Chair of Chemical Biology. at Scripps Look.

“We are also using our methods to develop improved processes for one-ton scale production of lactones used by chemical manufacturers,” Yu says.

“Catalyst-controlled site-selective methylene C–H lactonization of dicarboxylic acids” was co-authored by Hau Sun Sam Chan, Ji-Min Yang, and Jin-Quan Yu of Scripps Research.

Funding was provided by the National Institute of General Medical Sciences (2R01GM084019) and the Croucher Foundation.

About Scripps Research

Scripps Research is an independent, nonprofit biomedical institute ranked the world’s most influential for impact on innovation by the Nature Index. We advance human health through profound discoveries that address pressing medical concerns around the world. Our drug discovery and development division, Calibr, works hand-in-hand with scientists from all disciplines to bring new drugs to patients as quickly and efficiently as possible, while teams at the Scripps Research Translational Institute harness genomics , digital medicine and advanced computing to understand individual health and make healthcare more efficient. Scripps Research also trains the next generation of top scientists at our Skaggs Graduate School, consistently named one of America’s Top 10 Chemistry and Biological Sciences programs. Learn more at

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of press releases posted on EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Source link

About Donald P. Hooten

Check Also

The 369 Manifestations Method: How to Make Your Therapy Sessions Work

Psychologist Nancy Sokarno walks us through the 369 Manifestations Method and how to get the …