Phosphorylation of quercetin with trivalent phosphorus reagents

Abstract

Previously we initiated research into phosphorylation of the well-known flavonoid, dihydroquercetin I, with trivalent phosphorus reagents [1,2]. Now we report about the possibility of extending this reaction on quercetin II, a compound that has a more complex structure than flavonoid I.The partially protected quercetin derivatives, viz. quercetin 3,3`,4`,7-tetrabenzylate (III) and 3,3`,4`,7-tetraacetate (IV) contain a free hydroxy group in the C 5 position [3, 4]. Phosphorylation was carried out with 2-chloro-and 2-amido-4,4-dimethyl-1,3,2-dioxaphosphorinanes. The best yields of the target products were achieved when acid chlorides were used. 58 d go E d ; 6 d j R<O OR<< O OR OR OR 7 5 3 4< 3< O III!VIII R = R< = Bn, R<< = ; = !P < O < O P O Me Me (V); R = Ac, R< = R = R< = Bn, R<< = H (III); R = R< = Ac, R<< = H (IV); ; = !P < O < O P O Me Me , R<< = H (VI); R = R< = Bn, R<< = ; = P < O < O P O Me Me m i S (VII); R = Ac, R< = ; = P < O < O P O Me Me m i S , R<< = H (VIII).Phosphorylation of tetrabenzyl derivative III gave phosphite V. The 1 H NMR spectrum of this compound contains all expected signals, and the signal of the 5-OH proton of the starting flavonoid is absent.The 13 C NMR spectrum shows a 3 J(PC 5 ) coupling constant of 6.6 Hz.Phosphorylation of compound IV under the same conditions resulted in quantitative formation of phosphite VI with the phosphorinane ring at the C 7 atom. The 1 H NMR spectrum of compound VI contains a 5-OH proton signal.Phosphites V and VI were reacted with sulfur in the presence of a catalytic amount of triethylamine. Thiophosphates VII and VIII were isolated by column chromatography.