A THEORETICAL AND EXPERIMENTAL STUDY OF THE SYNTHESIS AND REACTIVITY OF THE (±)-LICARIN A

Abstract

Lignans and neolignans, which represent about 90% of the reported lignoids in the literature, have attracted the interest of researchers due to the wide range of plant species, structural variety and numerous biological activities such as antiviral, antitumor, trypanocidal, analgesic, anti-inflammatory, anti-mutagenic, antimicrobial, antifungal, leishmanicidal, among others. Thus, the chemical transformation and biological evaluation of new derivatives of this class of secondary metabolites are key actions for the expansion of scientific knowledge and obtaining of the potentially bioactive substances. This study aimed to synthesize the dihydrobenzofuran neolignans (±)-licarin A with use of oxidative coupling reactions. Computational calculations (DFT - Density Functional Theory) were performed to give insights into the electronic structure and to determine the possible reactive sites for nucleophilic and electrophilic attack on the (±)-licarin A. The neolignan was obtained as a white solid (m.p. = 105-107 o C) with yield of 98.3%. The structural elucidation was performed by 1 H and 13 C NMR. The results confirm (compared with data reported in literature) that the synthetic route is appropriate for obtaining the (±)-licarin A. Frontier molecular orbitals (HOMO and LUMO), as well as the Fukui functions for nucleophilic (𝒇𝒌 +) and electrophilic (𝒇𝒌-) attack, were used to determine the reactivity sites on the (±)-licarin A. It was observed that both the electrophilic and nucleophilic attack occur in the same molecular region, especially at the C1', C4', C8', and O (ether) and C4', C6' and C8' atoms, respectively.