Figure 5.

(A) Syntheses of glucocorticoid analogues 90, 91, 92, 97, and 98. ^aReagents and conditions: (a) HCHO (37%), HCl (conc.), CHCl₃, 23 °C, 61%; (b) ethylene glycol, TsOH (cat.), benzene, reflux, 60%; (c) hν, Vycor filter, 60 h, 57%; (d) hν, N-iodosuccinimide (3.0 equiv), Li₂CO₃ (3.5 equiv), MeOH:PhCH₃ = 1:20, 23 °C, 20 min; (e) 2:10:1 TFA:CH₂Cl₂:H₂O, 0 °C, 2 h, 67% over 2 steps; (f) AgF (3.8 equiv), 10:1 MeCN:H₂O, 23 °C, 98%; (g) NaBH₄ (0.9 equiv), 1:1 CH₂Cl₂:MeOH, 0 °C, 2 h, 72%; (h) HCl (6 N), TFA, 23 °C, 30 min, 53%; (i) MsCl (1.3 equiv), Et₃N (2.0 equiv), DMAP (0.1 equiv), CH₂Cl₂, 0 to 23 °C, 40 min; LiCl (1.3 equiv), DMF, 60 °C, 3 h, 81%; (j) TMSCl (4.0 equiv), NaI (40.0 equiv), Ac₂O, 0 °C, 1 h; Selectfluor (1.3 equiv), MeCN, 0 °C, 1 h, 49%; for 97, (k) (EtCO)₂O (1.5 equiv), TMSOTf (0.45 equiv), CH₂Cl₂, 0 °C, 1 h; (l) HCl (6 N), 75 °C, 5 h, 44% over 2 steps, and for 98, (k) (EtCO)₂O (1.5 equiv), TMSOTf (0.45 equiv), CH₂Cl₂, 0 °C, 1 h, 91%; (l) HCl (6 N), μW, 120 °C, 15 min, 31%. (B) GR binding and anti-inflammatory efficacy of steroid analogues and reference compounds. ^bGR, glucocorticoid receptor. ^cIL-12B, interleukin-12B; MR, mineralocorticoid receptor. ^dThe number in parentheses is the corresponding efficacy value. ^eThe abbreviation “nd” indicates that examination is not done.