Advances and challenges in the synthesis of highly oxidised natural phenols with antiviral, antioxidant and cytotoxic activities

Polyphenols are a family of organic compounds characterized by a wide range of biological activities. Among natural polyphenols, the products derived from shikimic and polyketide biogenic pathways, such as lignans, neolignans, cardanols and flavonoids are of special interest owing to their powerful antioxidant, antitumoral, antimitotic, antiviral, cardiovascular and immunosuppressive activity. The biological activity of polyphenols can be finely tuned by the oxidation state of the molecule. Polyphenols are subject to oxidative metabolism in the cell by cytochrome p-450 dependent enzymes, mainly at reactive benzyl and aryl positions of the molecule, to yield highly oxidised derivatives, namely quinones, hydroquinones, semiquinones, catechols and others, whose biological activity can greatly differ from that of the parental compound. In fact, these derivatives are characterized by peculiar antitumoral, antioxidant and antiviral activities and show different chemical properties toward nucleophiles and electrophiles active sites in the cell. This behavior is dependent on the specific value of the redox potential in the cell. The low concentration of these metabolites in nature, and the difficulty to recover them from mammalian cells or fluids require novel procedures for their synthesis to collect adequate amounts of compounds for biological assays. On the other hand, only a few attentions has been devoted to design novel oxidative procedures for the synthesis of highly oxidised polyphenols characterized by higher biological activity. In this review, advances and challenges in the synthesis of natural and semi-synthetic highly oxidised polyphenols are reported focusing the attention in the recent years. Data on the antiviral, antioxidant and cytotoxic activities in vivo and in vitro systems for natural and semi-synthetic highly oxidised polyphenols are also reported, and the effect on the biological activity due to the introduction of one or more oxygen atoms in different reactive sites of the molecule, is discussed. © 2008 Bentham Science Publishers Ltd