Asymmetric Formal Synthesis of the Long-Acting DPP-4 Inhibitor Omarigliptin
A highly efficient asymmetric synthesis of the key tetrahydropyranol intermediate of DPP-4 inhibitor omarigliptin (1) is described. The successful development of a protecting-group- and precious-metal-free synthesis was achieved via the discovery of a practical asymmetric Henry reaction and the application of a one-pot nitro-Michael–lactolization–dehydration through-process. Other features of the synthesis include a highly efficient MsCl-mediated dehydration and a crystallization-induced dynamic resolution for exceptional ee and dr upgrade. The synthesis of this complex intermediate utilizes simple starting materials and proceeds in four linear steps.
Digital Commons Citation
Peng, F; Chen, Y; Chen, C Y.; and Dormer, P G., "Asymmetric Formal Synthesis of the Long-Acting DPP-4 Inhibitor Omarigliptin" (2017). Clinical and Translational Science Institute. 844.