Polyphenols are natural antioxidants present in plants with several biomedical effects, among which the arrest of tumor growth; although they have different structures, all are characterized by having aromatic rings, with one or more hydroxyl substituents. In this context, our aim is to prepare, by using a multistep procedure already developed by us, new analogs of flavonoids, tyrosol and resverastrol, with high degree of oxygenation and / or functionalized with lipophilic chains. For the synthesis of aromatic polyhydroxylated compounds we exploited a protocol developed in our laboratories consisting in 1) selective and environmentally sustainable bromination of easily available aromatic compounds 2) methoxylation with MeONa in the presence of CuBr 3) eventual demethylation with BBr3 or through oxidative demethylation with IBX or Oxone, reduction with hydrides or, alternatively, by enzymatic conversion with lipase to obtain the final product. Actually our attention is also focused on the development of a synthetic strategy for the preparation of benzofuran and benzopyran derivatives, a group of biological active heterocycles extracted from different plants and used in traditional medicine of some countries. To synthesize 2,3‑diidrobenzofuranes, benzofuranes and benzopyranes scaffolds for the preparation of more complex molecules, we are investigating the use of catalysts of the copper-free ligands, as an alternative to ruthenium, palladium and other transition metals, which must be assisted by complex ligands. The use of salts of copper (I) is particularly advantageous in terms of cost and ease of operation. A procedure recently developed in our laboratory will be used to prepare analogs of resveratrol. The procedure is based on an easy and environmentally friendly formation of a phenonium ion, exploiting the ability of phenethyl alcohol carboxymethylesters to rearrange. The reactivity of this cation, highly unstable, towards nucleophiles, also weak, allows the synthesis of a large number of phenethyl derivatives, including stylbenoid structures, using anisole derivatives as nucleophile .
New polyphenols and their anticancer activity / Sappino, Carla; Righi, Giuliana; Bovicelli, Paolo; Bottaro, Fabrizio; Tomei, Michela; Mandic', Emanuela. - STAMPA. - (2015). (Intervento presentato al convegno International workshop on “biochemistry, physiology and pharmacology of oxidative stress” tenutosi a Roma nel 2-4 Luglio 2015).
New polyphenols and their anticancer activity
SAPPINO, CARLA;TOMEI, MICHELA;MANDIC', EMANUELA
2015
Abstract
Polyphenols are natural antioxidants present in plants with several biomedical effects, among which the arrest of tumor growth; although they have different structures, all are characterized by having aromatic rings, with one or more hydroxyl substituents. In this context, our aim is to prepare, by using a multistep procedure already developed by us, new analogs of flavonoids, tyrosol and resverastrol, with high degree of oxygenation and / or functionalized with lipophilic chains. For the synthesis of aromatic polyhydroxylated compounds we exploited a protocol developed in our laboratories consisting in 1) selective and environmentally sustainable bromination of easily available aromatic compounds 2) methoxylation with MeONa in the presence of CuBr 3) eventual demethylation with BBr3 or through oxidative demethylation with IBX or Oxone, reduction with hydrides or, alternatively, by enzymatic conversion with lipase to obtain the final product. Actually our attention is also focused on the development of a synthetic strategy for the preparation of benzofuran and benzopyran derivatives, a group of biological active heterocycles extracted from different plants and used in traditional medicine of some countries. To synthesize 2,3‑diidrobenzofuranes, benzofuranes and benzopyranes scaffolds for the preparation of more complex molecules, we are investigating the use of catalysts of the copper-free ligands, as an alternative to ruthenium, palladium and other transition metals, which must be assisted by complex ligands. The use of salts of copper (I) is particularly advantageous in terms of cost and ease of operation. A procedure recently developed in our laboratory will be used to prepare analogs of resveratrol. The procedure is based on an easy and environmentally friendly formation of a phenonium ion, exploiting the ability of phenethyl alcohol carboxymethylesters to rearrange. The reactivity of this cation, highly unstable, towards nucleophiles, also weak, allows the synthesis of a large number of phenethyl derivatives, including stylbenoid structures, using anisole derivatives as nucleophile .I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
