Maurizio Barontini

Convenient synthesis of hydroxytyrosol and its lipophilic derivatives from tyrosol or homovanillyl alcohol.

Hydroxytyrosol, a naturally occurred o-phenolic compound exhibiting antioxidant properties, was synthesized by a three-step high-yielding procedure from natural and low-cost compounds such as tyrosol or homovanillyl alcohol. First, the efficient chemoselective protection of the alcoholic group of these compounds was performed by using dimethyl carbonate (DMC) as reagent/solvent; second, the oxidation with 2-iodoxybenzoic acid (IBX) or Dess-Martin periodinane reagent (DMP) and in situ reduction with sodium dithionite (Na2S2O4) allowed the preparation of carboxymethylated hydroxytyrosol; finally, by a mild hydrolytic step, hydroxytyrosol was obtained in high yield and purity, as confirmed by NMR spectra and HPLC profile. By using a similar methodology, lipophilic hydroxytyrosol derivatives, utilized as additives in pharmaceutical, food, and cosmetic preparations, were prepared. In fact, at first the chemoselective protection of the alcoholic group of tyrosol and homovanillyl alcohol was performed by using acyl chlorides without any catalyst to obtain the corresponding lipophilic derivatives, and then these compounds were converted in good yield and high purity into the hydroxytyrosol derivatives by oxidative/reductive pathway with IBX or DMP and Na2S2O4.

Synthesis and Structure/Antioxidant Activity Relationship of Novel Catecholic Antioxidant Structural Analogues to Hydroxytyrosol and Its Lipophilic Esters

A large panel of novel catecholic antioxidants and their fatty acid or methyl carbonate esters has been synthesized in satisfactory to good yields through a 2-iodoxybenzoic acid (IBX)-mediated aromatic hydroxylation as the key step. The new catechols are structural analogues of naturally occurring hydroxytyrosol (3,4-DHE). To evaluate structure/activity relationships, the antioxidant properties of all catecholic compounds were evaluated in vitro by ABTS assay and on whole cells by DCF fluorometric assay and compared with that of the corresponding already known hydroxytyrosyl derivatives. Results outline that all of the new catechols show antioxidant capacity in vitro higher than that of the corresponding hydroxytyrosyl derivatives. Less evident positive effects have been detected in whole cells experiments. Cytotoxicity experiments, using MTT assay, on a representative set of compounds evidenced no influence in cell survival.

Expedient Synthesis of Hydroxytyrosol and its Esters

Abstract An efficient and friendly method for obtaining hydroxytyrosol from tyrosol, a component of olive waste, is reported. Hydroxytyrosol also may be obtained in the form of enzymatically convertible precursors (e.g., hydroxytyrosyl acetate), thus increasing the stability of the active principle.

The Effects of Borate Minerals on the Synthesis of Nucleic Acid Bases, Amino Acids and Biogenic Carboxylic Acids from Formamide

The thermal condensation of formamide in the presence of mineral borates is reported. The products afforded are precursors of nucleic acids, amino acids derivatives and carboxylic acids. The efficiency and the selectivity of the reaction was studied in relation to the elemental composition of the 18 minerals analyzed. The possibility of synthesizing at the same time building blocks of both genetic and metabolic apparatuses, along with the production of amino acids, highlights the interest of the formamide/borate system in prebiotic chemistry.

A selective de-O-methylation of guaiacyl lignans to corresponding catechol derivatives by 2-iodoxybenzoic acid (IBX). The role of the catechol moiety on the toxicity of lignans

We report here the first selective de-O-methylation of a large panel of guaiacyl lignans to the corresponding catechol derivatives by using IBX as primary oxidant under green conditions (dimethyl carbonate-H(2)O solvent) through an in situ reduction procedure. The influence of the catechol moiety on the cytotoxicity and genotoxicity of new lignan derivatives has been investigated. The results obtained indicated that the presence of the catechol moiety sharply enhances the clastogenic potential (e.g. induction of chromosomal aberrations), the cytotoxicity and the modulation of cell cycle progression with respect to the parent compounds. Thus, despite the in vitro antioxidant activity usually described for catechol derivatives, our results show for the first time the generation of a clastogenic potential, highly indicative of a long-term genetic and cancer risk.

New lipophilic piceatannol derivatives exhibiting antioxidant activity prepared by aromatic hydroxylation with 2-iodoxybenzoic acid (IBX).

Piceatannol (E-3,5,3’,4’-tetrahydroxystilbene) is a phytoalexin synthesized in grapes in response to stress conditions. It exhibits strong antioxidant and antileukaemic activities due to the presence of the catechol moiety. To modify some physical properties like solubility, and miscibility in non-aqueous media some new previously unreported piceatannol derivatives having lipophilic chains on the A-ring were prepared in good yields by a simple and efficient procedure. The key step was a chemo- and regioselective aromatic hydroxylation with 2-iodoxybenzoic acid (IBX). The new compounds showed antioxidant activity and seemed promising for possible applications as multifunctional emulsifiers in food, cosmetic and pharmaceutical fields.

Dimethyl carbonate in the regio- and stereocontrolled opening of three-membered heterocyclic rings

In an attempt to replace harmful or carcinogenic solvents (such as dichloromethane, acetone, etc.) with non-harmful and greener ones, the possibility of performing four already developed ring-opening methodologies in a more eco-friendly media, such as DMC, has been investigated. The results show that the usual employed solvents (CH2Cl2, Et2O, CH3CN, etc.) can be easily replaced by DMC: not only the stereo- and regioselectivity is conserved, but also the work-up is simplified to a filtration, therefore reducing considerably the amount of solvents employed in the processes, and all the reactions are performed at room temperature, even the ones previously reported at low temperatures.

New Efficient Synthesis of Ubiquinones

Abstract A strategy for the ecofriendly and high‐yielding synthesis of ubiquinones starting from simple materials and using mild conditions is reported. CoQ1, CoQ2, CoQ3, and CoQ9 were prepared.

Synthesis and biological evaluation of gallic acid analogs

A novel and efficient synthesis of pyrogallol moiety through a copper(I)-mediated C–O bond forming reaction is described. In particular, syntheses of 3,4,5-trihydroxyphenethyl alcohol and its methyl derivative are reported. Particular attention to dimethyl carbonate as an eco-friendly solvent/reactant has been paid, in order to improve the eco-compatibility of the whole synthetic pathway. Furthermore, the genotoxicity, cytotoxicity and the antioxidant activity of 3,4,5-trihydroxyphenethyl alcohol and its methyl derivative have been investigated.

Efficient synthesis of scutellarein

Scutellarein is a component of Scutellaria, recently known as a potent cytotoxic agent on human leukaemia cells. The aim of this study was the synthesis of scutellarein and its methylated derivative. The new features are the innovating method to afford flavones from flavanones and the A-ring regioselective bromination step that lead to the target molecule by a facile and high-yielding pathway.