A Condensed, Scalable Synthesis of Racemic Koningic Acid
Guillaume Barbe1, David Chai2, Bin Chen2
1Rheos Medicines Inc., 38 Sidney Street Suite 200, Cambridge, Massachusetts 02139, United States.
Abstract:
The natural product koningic acid (KA) is a selective covalent inhibitor of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a critical node in the glycolysis pathway. While KA is available commercially, sources are limited and its cost becomes rapidly prohibitive beyond the milligram scale. Additionally, a practical and flexible synthetic route to KA and analogs remains to be developed. Here we detail a new route that is operationally safer, scalable and offers a five-step reduction in the previously reported longest linear sequence.
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