In July, the Sorensen Lab, which specializes in total synthesis and catalysis at the Frick Chemistry Laboratory, published a paper highlighting the results of the group’s success in shortening the procedure for synthesizing the complex molecule pleurotin.
A vast body of evidence underscores the molecule’s potential as a key agent for antibiotic treatments and tumor inhibitors against cancer.
The paper, titled “A Concise Synthesis of Pleurotin Enabled by a Nontraditional C-H Epimerization,” was published in the Journal of the American Chemical Society (JACS). Professor of Chemistry Dr. Erik Sorensen and a third-year graduate student in his lab, John Hoskin, served as co-authors of the groundbreaking paper.
Employing techniques such as Diels-Alder reactions and a radical epimerization — an elaborate method of reconfiguring the molecular structure of a component known as the “stereocenter” (of which pleurotin has eight) — Hoskin and Dr. Sorensen managed to synthesize pleurotin in a procedure unparalleled in its concision.
The last successful synthesis of the molecule occurred in 1988 and required 26 steps — the newly developed process requires only eight. In 2008, the Sorensen Lab decided to undertake the challenge of facilitating the synthesis of this molecule, an enterprise that was plagued by setback after setback, according to Sorensen.
Sorensen elaborated that the overwhelming complications that arose during the process of achieving a shortened pleurotin synthesis compelled the lab to relegate the project to the backburner.
“We shelved this project for about 12 years and decided to revisit it with some new, more modern ideas,” Sorensen wrote in an email to The Daily Princetonian.
With recent advances in photochemical catalysis, the lab returned to the pleurotin synthesis project with renewed optimism and interest.
“Earlier this year, my outstanding graduate student, John Hoskin, created a key intermediate, the foundation for our new approach, using only five chemical reactions,” Sorensen continued.
Hoskin could not be reached for comment by the ‘Prince’ by the time of publication.
Sorensen explained that despite Hoskin’s innovative approaches, the team struggled to overcome certain obstacles on the road to a shortened pleurotin synthesis process. Sorensen emphasized that finding a way to reconfigure the molecule proved particularly formidable.
The team achieved the needed restructuring, utilizing a hydrogen atom transfer.
“This key step worked and is rightly viewed as the cornerstone transformation in our synthesis,” he wrote.
During the process of creating the abbreviated pleurotin synthesis, Hoskin made notably efficient headway in achieving the synthesis portion of the procedure, amazing Sorensen.
“Once we hit upon the [eight]-step route to the core architecture of pleurotin, it took my coauthor John Hoskin only one week to move through the synthesis. This is an impressively short period of time with a project of this sort,” Sorensen wrote.
With the achievement of the shortened synthesis of pleurotin, the Sorensen Lab is currently pursuing related avenues of research, with the ultimate goal of rendering pleurotin a viable anti-cancer screening candidate. In the future, these candidates could serve as an alluring target for pharmaceutical companies seeking to harness the promising properties of pleurotin to devise novel drugs and therapies against cancer.
“Our current aim is to leverage this chemistry in short syntheses of an expanded family of structures having key features of pleurotin. This research will be part of the ongoing effort to elucidate and extend the therapeutic potential of this natural product,” Sorensen wrote.
Amy Ciceu is a senior writer who often covers research and COVID-19-related developments. She also serves as a Newsletter Contributor. She can be reached at aciceu@princeton.edu.
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