Synthesis of Chiral Tetrahydrofuran Building Blocks from Pantolactones: Application in the Synthesis of Empagliflozin and Amprenavir Analogs

Abstract

Chiral 4,4–dimethyl tetrahydrofuran (THF) derivatives were synthesized from commercially available D‐(–)/ l‐(+) pantolactones, which can serve as chiral building blocks in medicinal chemistry. In addition, two of the synthesized building blocks were utilized for the synthesis of new amprenavir (HIV protease inhibitor) and empagliflozin (anti‐diabetic) analogs. The synthesized analogs may have beneficial effects in terms of pharmacokinetics and modulation of bioactivity.

Comprehensive Strategies to Bicyclic Prolines: Applications in the Synthesis of Potent Arginase Inhibitors

“…Aqueous HCl promoted the deprotection of the TBS and methyl ether in one step and directly afforded the cyclized thermodynamically stable cis -cyclic acetal 71 . The reduction of acetal 71 under the reductive esterification conditions afforded cyclic ether 72 in 77% yield . The hydroboration of 72 and global deprotection utilizing BBr 3 afforded bicyclic proline 7 .…”

“…The reduction of acetal 71 under the reductive esterification conditions afforded cyclic ether 72 in 77% yield. 48 The hydroboration of 72 and global deprotection utilizing BBr 3 afforded bicyclic proline 7.…”