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Updated: Apr 23, 2026

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Asymmetric synthesis of highly functionalized tetrahydropyran DPP-4 inhibitor
Feng Xu1, Michael J Zacuto, Yoshinori Kohmura
1Process Chemistry, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
Abstract:
A practical synthesis of a highly functionalized tetrahydropyran DPP-4 inhibitor is described. The asymmetric synthesis relies on three back-to-back Ru-catalyzed reactions. A Ru-catalyzed dynamic kinetic resolution (DKR) reduction establishes two contiguous stereogenic centers in one operation. A unique dihydropyran ring is efficiently constructed through a preferred Ru-catalyzed cycloisomerization. Hydroboration followed by a Ru-catalyzed oxidation affords the desired functionalized pyranone core scaffold. Finally, stereoselective reductive amination and subsequent acidic deprotection afford the desired, potent DPP-4 inhibitor in 25% overall yield.
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