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Efficient Syntheses of KLS-13019 Using Palladium Mediated Cross Couplings.

William A KinneyMark E McDonnellStanley FreemanNick SimonsChao HanLanyi Yang
Published in: Tetrahedron letters (2023)
KLS-13019 is a structural analogue of cannabidiol, that shows improved bioavailability and potency in both preventing and reversing paclitaxel-induced neurotoxicity in vitro and in vivo. KLS-13019 was selected as a development candidate and attention was turned to development of a scalable synthesis. The original synthesis of KLS-13019 was not efficient, regioselective, or high yielding. Two new syntheses are reported that make use of the palladium catalyzed cross couplings to a chemically advanced intermediate 5 , dramatically shortening (3-4 steps) and improving the overall yield. In addition, a convenient one pot Boc-cleavage and acetylation procedure is described to avoid impurities generated from a step-wise process.
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