Synthesis and evaluation of 9-deoxy analogues of (−)-thysanone, an inhibitor of HRV 3C protease

Roles of the Picornaviral 3C Proteinase in the Viral Life Cycle and Host Cells

“…Through synthesis of analogues and the biological evaluation of (−)-thysanone, the 2-methylene analogue of (−)-thysanone has lost the capacity to inhibit HRV 3C pro [ 147 ]. However, 9-deoxy analogues of (−)-thysanone display better inhibitory ability than the natural product [ 148 ]. Studies of herbs have demonstrated that flavonoids, such as fisetin and rutin, can inhibit the enzymatic activity of EV 71 3C pro in a dose-dependent manner with IC 50 values of 85 and 110 μM, respectively [ 149 ].…”

Stereoselective Total Synthesis of the Dimeric Naphthoquinonopyrano-γ-lactone (−)-Crisamicin A: Introducing the Dimerization Site by a Late-Stage Hartwig Borylation

“…Having met the stereochemical exigencies of our endeavor (Scheme ), the naphthohydroquinonopyrano-γ-lactone 6 was dimerized in steps (a) and (b) of Scheme . Step (a), a Hartwig borylation, succeeded with pinacolborane, 2.5 mol % of [{Ir­(μ-OMe)­COD} 2 ], and 5 mol % of 4,4′-di- tert -butyl-2,2′-dipyridyl. , It activated the least hindered naphthyl–H bond of substrate 6 with perfect regioselectivity; that is, it attacked meta relative to both the MeO group and the annulated ring. The expected boronic ester 14 was so labile that it could not be purified by flash chromatography but only by filtration over silica.…”

“… a Reagents and conditions: (a) Pinacolborane (2.7 equiv), [{Ir­(μ-OMe)­COD} 2 ] (2.5 mol %), 4,4′-di- tert -butyl-2,2′-dipyridyl (5 mol %), THF, 80 °C, 1 day; filtration over silica; (b) KF (3.7 equiv), B­(OH) 3 (4.6 equiv), O 2 (1.0 bar), PdCl 2 (PPh 3 ) 2 (20 mol %), THF/H 2 O (4:1), rt, 2.5 h; 46% over two steps; (c) (NH 4 ) 2 [Ce­(NO 3 ) 6 ] (4.7 equiv), MeCN/H 2 O (2:1), rt, 20 min; 65%; (d) AlCl 3 (12 equiv), CH 2 Cl 2 , 0 °C, 20 min; to rt, 3 h; 67% …”