Selective Alkylations of Certain Phenolic and Enolic Functions with Lithium Carbonate/Alkyl Halide

Structure-activity Relationships for α-Glucosidase Inhibition of Baicalein, 5,6,7-Trihydroxyflavone: the Effect of A-Ring Substitution

“…13) Methylation of 1 with methyl iodide and potassium carbonate gave 5-hydroxy-6,7-dimethoxyflavone (11) and 5,7-dihydroxy-6-methoxyflavone (12), 14) while 5,6-dihydroxy-7-methoxyflavone (13) was obtained selectively from 1 with methyl iodide and lithium carbonate. 15) UV shift tests for the position of 5 and 7-OH on hydroxyflavones, and comparison of mass and NMR spectra with reference data confirmed the structures of 3, 6, 8, 9, and 11-13.…”

“…17) Hydrogenation of 14a afforded 21a, which was then treated with boron tribromide to give 8-amino-5,6,7-trihydroxyflavone (21). 18) Compound 11 was formylated with Duff reaction conditions, using hexamethylenetetramine and TFA to yield 8-formyl-5-hydroxy-6,7-dimethoxyflavone (15a), which was demethylated to obtain 8-formyl-5,6,7-trihydroxyflavone (15). 19) Compound 15 was reduced with sodium cyanoborohydride to give 5,6,7-trihydroxy-8-methylflavone (19) in 65% yield.…”

“…These 8-position substitutions (14-17, 19-21) of 1, which resulted in a disadvantage for -glucosidase inhibitory activity, was then due possibly to a steric interference to the interaction between the 5,6,7-trihydroxyl group of 1 and the enzyme. Compound 22, which has a large piperidinomethyl group at position 8, was also inactive, while 18 (IC 50 ¼86 M) which has a less bulky fluorine at position 8 showed moderate activity compared to other 8-substitued 5,6,7-trihydroxyflavones (14)(15)(16)(17)(19)(20)(21), suggesting that excess steric bulkiness around position 8 of 1 is detrimental for the potent inhibitory activity.…”

“…To a stirred solution of 5-hydroxyflavone (3) (4.76 g, 20 mmol) in water (100 ml) containing sodium hydroxide (4 g, 100 mmol) was added dropwise during 4 hr a solution of potassium persulfate (6 g, 22 mmol) in water (200 ml), the temperature being kept at [15][16][17][18][19][20] C. After 24 hr, the solution was acidified to pH 4-5 and filtered. The filtrate was extracted twice with ether.…”

“…We used the Hammett substituent constant 25) to evaluate the electronic influence of 1 and 14-21 (Table 2). An introduction of an electron-withdrawing group (14)(15)(16)(17) at position 8 of 1 resulted in disappearance ofglucosidase inhibitory activity, though 18 was tolerated with a minor loss of potency. However, 19-21, which have an electron-donating group at position of 8, were also inactive, although 20 (IC 50 ¼960 M) and 21 (IC 50 ¼1000 M) were very weak inhibitors.…”