Experiments with Khellin. I. The Preparation of Desmethylkhellin and Some of its Derivatives

A New Class of Blockers of the Voltage-Gated Potassium Channel Kv1.3 via Modification of the 4- or 7-Position of Khellinone

“…4-Ethoxy-9-methoxy-7-methyl-furo[3,2- g ]chromen-5-one (4f). Compound 3f (110 mg, 0.45 mmol) and ethyl iodide (0.35 mL, 4.5 mmol) were treated as described under General Procedure A to afford 4f (110 mg, 90%) as a colorless solid: Mp 104−106 °C lit . 109−110 °C (EtOH/H 2 O); 1 H NMR (CDCl 3 ) δ: 1.43 (t, J = 10.5 Hz, 3H), 2.35 (s, 3H), 4.16 (m, 5H), 6.03 (s, 1H), 6.93 (d, J = 3.2 Hz), 7.58 (d, J = 3.2 Hz); 13 C NMR (CDCl 3 ) δ: 15.6, 20.0, 61.3, 71.2, 105.2, 110.4, 120.5, 129.9, 145.4, 146.0, 147.0, 148.5, 164.0, 178.1, 196.2; MS (ES + ) m / z 275.1 (M + H + ).…”

“…An early study from 1952 described the formation of 4-alkoxy khellins by the selective demethylation of khellin with acid and subsequent alkylation. 26 A restricted number of compounds with C1-C4 alkoxy substituents in the 4-position in combination with any alkoxy substitution at the 7-position were afforded in a six-step synthesis of khellinone derivatives from pyrogallol. 27 Other workers bis-demethylated khellin to dinorkhellin either in a single step using magnesium iodide in ether, 28 or in two steps through the khellin quinone, 29,30 followed by alkylation to give 4-or 9-alkoxy-substituted khellins.…”

“…Limited derivatization at these positions in khellinone and the related khellin has been previously reported in the literature. An early study from 1952 described the formation of 4-alkoxy khellins by the selective demethylation of khellin with acid and subsequent alkylation .…”