Enantioselective Synthesis of Dioxatriquinane Structural Motifs for HIV-1 Protease Inhibitors Using a Cascade Radical Cyclization

Arun K Ghosh; Chun-Xiao Xu; Heather L Osswald

doi:10.1016/j.tetlet.2015.01.019

Enantioselective Synthesis of Dioxatriquinane Structural Motifs for HIV-1 Protease Inhibitors Using a Cascade Radical Cyclization

Tetrahedron Lett. 2015 Jun 3;56(23):3314-3317. doi: 10.1016/j.tetlet.2015.01.019.

Authors

Arun K Ghosh¹, Chun-Xiao Xu¹, Heather L Osswald¹

Affiliation

¹ Department of Chemistry and Department of Medicinal Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, United States.

Abstract

Synthesis of novel HIV-1 protease inhibitors incorporating dioxatriquinane-derived P2-ligands is described. The tricyclic ligand alcohol contains five contiguous chiral centers. The ligand alcohols were prepared in optically active form by an enzymatic asymmetrization of mesodiacetate, cascade radical cyclization, and Lewis acid catalyzed reduction as the key steps. Inhibitors with dioxatriquinane-derived P2-ligands exhibited low nanomolar HIV-1 protease activity.

Keywords: Cascade; Dioxatriquinane; HIV-1 protease; Inhibitor; Radical.

Abstract

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