Scripps method builds branched drug molecules 4x faster
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- Scripps Research scientists published a method in Science that replaces expensive silane additives with manganese metal and a mild acid (lutidinium) to power cobalt-nickel dual catalysis toward branched molecular structures used in many medicines.
- Ryan Shenvi, senior author and professor at Scripps Research, said the method "solves a selectivity problem that challenged us for years" and lays the groundwork to access iteratively branching materials found in metabolites, fragrances, and drugs.
- Milo Smith, a postdoctoral researcher in the Shenvi lab, said the approach lets chemists reach target branched compounds up to four times faster than previous methods, a meaningful time savings when scientists are exploring many new molecules at once.
- The Shenvi lab used the method to produce more than 50 new branched compounds in a single chemical reaction that would previously have required multiple labor-intensive steps, and the products tolerate sensitive groups including alcohols and amines.
- Co-first author Chunyu Li said the team was surprised manganese worked because it is a weaker reducing agent, but paired with the right acid it hits a narrow chemical window that activates cobalt without disrupting nickel.
- The branched products are not chemical dead ends: the product alkene is stable under reaction conditions and can be isolated and reacted again, letting chemists iterate on bond formation to build more complex architectures.
- The same manganese-lutidinium system also improved a related process called hydroarylation and enabled alkene isomerization, suggesting "metal hydride selection" could become a general tool across synthesis.
- The publication is Li et al, "Cross- and branched-selective hydroalkenylation by metal hydride selection," in Science (2026), DOI: 10.1126/science.aeb2389, provided by The Scripps Research Institute.
Why it matters: Early-stage medicinal chemists exploring many branched drug candidates gain a reagent system that is cheaper, easier to handle, and more recyclable than standard silanes, with the Shenvi lab reporting up to 4x faster access to target branched compounds. That speedup, combined with the method's production of 50+ new compounds in single-step reactions, lowers the cost of building the rare branched building blocks that gate many drug scaffolds.
