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.
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.
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.