ACS Central Science
February 14, 2024
Ryan A Shenvi
37 citations
Natural product synthesis began from human curiosity about matter and its medicinal uses, yielding molecules like strychnine, morphine, psilocybin, and ephedrine. The field advanced organic chemistry by studying nonmetal elements but later contracted in the United States as pharmaceutical companies divested and academic focus shifted to catalysis and applications-driven research. Now, with widespread bioassays and chemical biology tools, synthesis gains new relevance. Digital encoding and data science can apply hard-won insights to new challenges, allowing chemists to surpass natural properties. The essay contextualizes natural product synthesis for a broad audience and anticipates a bright future at the intersection of synthesis and biology.
ACS Central Science
July 3, 2025
Mara Johnson-Groh
3 citations
Some scientists believe that incorporating secondary compounds from psychedelic mushrooms could improve pharmaceutical drugs, but due to limited data, other researchers remain skeptical about this approach.
ACS Central Science
August 10, 2023
Bhawyanth Duvvuru, Myles W. Smith
Salvinorin A (SalA), the most potent naturally occurring hallucinogen, is a polycyclic terpenoid from Salvia divinorum that acts as a selective kappa-opioid receptor (KOR) agonist, a target for non-addictive analgesics. Its complex structure limits synthetic modifications. In this work, Shenvi, Bohn, and co-workers developed a concise synthetic route to SalA analogues that overcome the natural compound's liabilities, yielding compounds with improved activity, KOR-selectivity, and functional bias. This approach offers new opportunities for exploring KOR-selective compounds, which avoid the addictive effects associated with mu-opioid receptor activation, potentially addressing the societal burden of opioid abuse.
ACS Central Science
August 23, 2023
Sarah J Hill, Nathan Dao, Vuong Q Dang et al.
A new chemical synthesis method produces salvinorin analogs that are more potent, selective, stable, and functionally biased than the natural compound salvinorin A. These analogs target the kappa-opioid receptor and could serve as templates for next-generation pain relievers, anti-itch treatments, and dissociative hallucinogens. The synthesis uses a special organocatalyst and a cobalt-catalyzed cycloaddition to efficiently create a library of these complex molecules, overcoming previous difficulties in modifying their structure.
ACS Central Science
December 27, 2017
Jeremy J Roach, Yusuke Sasano, Cullen L. Schmid et al.
Deleting a single carbon atom (C20) from the complex plant metabolite salvinorin A stabilizes its molecular skeleton, simplifies its laboratory synthesis to just 10 steps, and preserves its high affinity and selectivity for the human kappa-opioid receptor. The work also introduces a general workflow for identifying structural changes that keep molecular complexity high while reducing synthetic complexity.