A palladium free, light driven method from Scripps and Bristol uses cheap, bench stable building blocks to forge the key carbon sugar bond that has kept the cost of SGLT2 inhibitors — drugs for type 2 diabetes, heart failure, and chronic kidney
Scripps Research and University of Bristol chemists report a new way to build the C-glycoside bond at the center of SGLT2 inhibitor drugs, the class of type 2 diabetes, heart failure, and chronic kidney disease treatments that includes canagliflozin, dapagliflozin, and empagliflozin. The method, described in Nature, uses light-promoted radical chemistry on cheap, bench-stable glycohydrazide building blocks to replace the palladium catalysts and protecting-group steps that have made the bond expensive to forge.
SGLT2 inhibitors work by blocking a sugar transporter in the kidney, dumping glucose into urine. They also cut heart-failure hospitalization and slow chronic kidney disease progression, which is why major guidelines now recommend them across all three conditions. The class is now widely prescribed, but the cost of the active pharmaceutical ingredient has been held up for years by a single synthetic step: snapping a carbon onto the right carbon of a sugar-derived ring so the molecule survives digestion. The standard route uses palladium catalysts, organic solvents, and protecting groups that have to be added and then removed, and the final price reflects the extra steps.
The Scripps-Bristol method skips palladium and protecting groups by generating a carbon radical directly from a sugar-derived glycohydrazide, a bench-stable building block in which a nitrogen-nitrogen bond is the leaving group. The Bristol lab, led by Varinder Aggarwal, contributes an alkene coupling that snaps an alkene acceptor onto the sugar radical. The Scripps lab, led by Phil Baran, contributes the nitrile-acceptor coupling that Baran's group had developed for other targets, in which a light-promoted step converts the glycohydrazide into a carbon radical at room temperature. Together the two pieces cover the most common C-glycoside bond patterns found in drug chemistry, and both rely on starting materials that are stable on the bench and prepared in one step from ordinary sugars.
Glycohydrazides are made from ordinary sugars, and the small-molecule partners in the reaction are simple carboxylic acid derivatives, which is why outlets have called the inputs "table sugar" and "vinegar." The metaphor hides what the reaction actually does. The transformation is a radical addition that snaps a carbon radical generated from a sugar precursor onto a partner molecule, forming the carbon-carbon bond that defines the drug class. As Aggarwal told the Scripps press office, the method is a "total game changer for manufacturing key medicines faster and more cost-effectively," citing the "operational simplicity" and the "ready availability of starting materials."
SGLT2 inhibitors are taken daily, often for life, and the molecules are no longer patent-protected in many markets. Generic manufacturers have not been able to undercut brand prices by much, because the active ingredient is still expensive to make. A route that removes a palladium catalyst, several protecting steps, or a high-temperature coupling could narrow the gap. The University of Bristol announced the paper on June 29, 2026, and the work was picked up by EurekAlert and Phys.org the same week.
The paper reports scope across model substrates and a handful of drug-relevant targets, including fragments that map onto the SGLT2 inhibitor scaffold. It does not report kilograms per batch, catalyst loading, or overall yield at production scale, which is the data a generic manufacturer would want to see before switching processes. Independent replication in a process-chemistry lab is the next milestone to watch, and a commercial pilot would be the milestone after that. Until those numbers are public, the cost story is qualitative. The chemistry is real, and the bond it builds is the one that has defined the price of this drug class for a decade.