Paolo Bovicelli

In vitro analysis of iron chelating activity of flavonoids

Flavonoids have been demonstrated to possess miscellaneous health benefits which are, at least partly, associated with iron chelation. In this in vitro study, 26 flavonoids from different subclasses were analyzed for their iron chelating activity and stability of the formed complexes in four patho/physiologically relevant pH conditions (4.5, 5.5, 6.8, and 7.5) and compared with clinically used iron chelator deferoxamine. The study demonstrated that the most effective iron binding site of flavonoids represents 6,7-dihydroxy structure. This site is incorporated in baicalein structure which formed, similarly to deferoxamine, the complexes with iron in the stoichiometry 1:1 and was not inferior in all tested pH to deferoxamine. The 3-hydroxy-4-keto conformation together with 2,3-double bond and the catecholic B ring were associated with a substantial iron chelation although the latter did not play an essential role at more acidic conditions. In agreement, quercetin and myricetin possessing all three structural requirements were similarly active to baicalein or deferoxamine at the neutral conditions, but were clearly less active in lower pH. The 5-hydroxy-4-keto site was less efficient and the complexes of iron in this site were not stable at the acidic conditions. Isolated keto, hydroxyl, methoxyl groups or an ortho methoxy-hydroxy groups were not associated with iron chelation at all.

A new route to 2-alkenyl-1,3-dicarbonyl compounds, intermediates in the synthesis of dihydrofurans

A two step synthetic strategy for obtaining 2-alkenyl-1,3-dicarbonyl compounds from the corresponding 1,3-dicarbonyl compounds is reported. The method is based on a Knoevenagel condensation and a Michael addition using a high order organocuprate procedure, and proves to be of general value. Obtained compounds are useful starting materials for the synthesis of furan derivatives.

Iron reduction potentiates hydroxyl radical formation only in flavonols

Flavonoids, substantial components of the human diet, are generally considered to be beneficial. However, they may possess possible pro-oxidative effects, which could be based on their reducing potential. The aims of this study were to evaluate the ability of 26 flavonoids to reduce ferric ions at relevant pH conditions and to find a possible relationship with potentiation of hydroxyl radical production. A substantial ferric ions reduction was achieved under acidic conditions, particularly by flavonols and flavanols with the catecholic ring B. Apparently corresponding bell-shaped curves displaying the pro-oxidant effect of flavonols quercetin and kaempferol on iron-based Fenton reaction were documented. Several flavonoids were efficient antioxidants at very low concentrations but rather inefficient or pro-oxidative at higher concentrations. Flavonols, morin and rutin were progressively pro-oxidant, while 7-hydroxyflavone and hesperetin were the only flavonoids with dose-dependent inhibition of hydroxyl radical production. Conclusively, administration of flavonoids may lead to unpredictable consequences with few exceptions.

An easy approach to dihydrofurans by one-step cyclisation of 2-alkenyl substituted 1,3-dicarbonyl compounds

Abstract Dihydrofuran derivatives were obtained by a simple one-step procedure involving an easy epoxidation of 2-alkenyl-1,3-dicarbonyl compounds by dimethyldioxirane prepared in situ and a subsequent cyclisation under the same basic reaction conditions.

Oxyfunctionalization of steroids by dioxiranes: Site and stereoselective C14 and C17 hydroxylation of pregnane and androstane steroids.

Dimethyldioxirane showed to be site and stereoselective in the CH oxygen insertion at C14 and C17 positions of pregnane and androstane steroids. Fine steric control and evidence for the influence of the carbonyl group on the dioxirane reactivity are reported.

In vitro evaluation of copper-chelating properties of flavonoids

Copper is an essential trace element involved in plenty of redox reactions in living systems, however, unbound copper ions cause damage to various biomolecules via excessive generation of reactive oxygen species. Flavonoids, ubiquitous plant secondary metabolites, possess complex effects on human health and chelation of transient metal ions is one of their proposed mechanisms of action. In this in vitro study, 26 flavonoids from various subclasses were screened for their interactions with both copper oxidation states at four (patho)physiologically relevant pH conditions (4.5, 5.5, 6.8 and 7.5) by two spectrophotometric approaches and compared with the clinically used copper chelator trientine. In a slightly competitive environment, the majority of flavonoids were able to chelate cupric ions, however, under more competitive conditions, only flavones and flavonols were able to chelate both cupric and cuprous ions. Apparently, the 2,3-double bond was essential for stable copper chelation. The most efficient copper chelation sites were the 3-hydroxy-4-keto group in flavonols and the 5,6,7-trihydroxyl group in flavones. On the other hand, the 3′,4′-dihydroxyl group was associated only with a weak activity. 3-Hydroxyflavone, kaempferol and partly baicalein were even more potent than trientine in the acidic environment, however, none of the tested flavonoids was able to surpass it at physiological pH or slightly acidic conditions. In conclusion, flavonoids possessing appropriate structural characteristics were efficient copper chelators and some of them were even more potent than trientine under acidic conditions.

Selective oxidation of diols by H2O2/TS-1 system and by DMDO

Abstract Selective oxidations of secondary hydroxyl groups vs. primary ones in 1,n-diols by TS-1/H2O2 catalitic system and by dimethyldioxirane, new reagents with low environmental pollution, are reported.

Improved Conversion of Vitamin D2 into the Windaus Ketone and Its Regioselective Hydroxylation Via Organoboranes at C26

Abstract The improved oxidative conversion of Vitamin D2 into the Windaus ketone as well as the regioselective hydroxylation via organoboranes at C26 of the title ketone is reported.

Efficient desymmetrization of 1,2 and 1,3 diols by dimethyldioxirane

Abstract Dimethyldioxirane was used to monooxidize 1,2 and 1,3 sec,sec-diols to the corresponding ketoalcohols, exploiting the inhibiting effect of the formed carbonyl group on the course of the process.

A mild preparation of α-halo-α,β-enones from cyclic enones

Abstract A simple one pot procedure for the selective transformation of cyclic enones into α-halo-α,β-enones is reported using dimethyldioxirane and metal halides/Amberlyst 15. The method appears particulary appealing for the preparation of labelled molecules for use with the CMIA techinique.