Synthesis and Antimicrobial Activity of δ-Viniferin Analogues and Isosteres

Abstract

The natural stilbenoid dehydro-δ-viniferin, containing a benzofuran core, has been recently identified as a promising antimicrobial agent. To define the structural elements relevant to its activity, we modified the styryl moiety, appended at C5 of the benzofuran ring. In this paper, we report the construction of stilbenoid-derived 2,3-diaryl-5-substituted benzofurans, which allowed us to prepare a focused collection of dehydro-δ-viniferin analogues. The antimicrobial activity of the synthesized compounds was evaluated against S. aureus ATCC29213. The simplified analogue 5,5′-(2-(4-hydroxyphenyl)benzofuran-3,5-diyl)bis(benzene-1,3-diol), obtained in three steps from 4-bromo-2-iodophenol (63% overall yield), emerged as a promising candidate for further investigation (MIC = 4 µg/mL).

Chemistry, Biosynthesis and Pharmacology of Viniferin: Potential Resveratrol-Derived Molecules for New Drug Discovery, Development and Therapy

“…Another study reported that the resveratrol dimer (dehydro-δ-viniferin), a natural stilbenoid with a benzofuran core, is a potential antimicrobial agent against Gram-positive bacteria, especially the foodborne pathogen, Listeria monocytogenes [107]. Listeria monocytogenes can infect both humans and animals, although it is difficult to control the pathogen due to its ability to build biofilms.…”

“…This bactere can cause several diseases, mainly gastroenteritis, endocarditis, rhombencephalitis, invasive listeriosis, septicemia, meningitis and neonatal infections; it can also lead to abortion [108]. Mattio et al [107] utilized various protocols to derive stilbenoid-derived 2,3-diaryl-5-substituted benzofurans and found that key stages, such as the demethylation of phenolic groups, are required. Staphylococcus aureus (S. aureus) ATCC29213 was used to test antibacterial activity and the results showed that 5,5 -(2-(4-hydroxyphenyl)benzofuran-3,5-diyl)bis(benzene-1,3-diol) analogue is an important potential compound for further investigation.…”

“…To develop synthetic procedures in order to investigate their biological activities, some methylated viniferins (14-16) were synthesized and characterized by spectral data [122]. Recently, a collection of dehydro-viniferin analogues were synthesized and evaluated for their antimicrobial activities [107]. Recently, a collection of dehydro-viniferin analogues were synthesized and evaluated for their antimicrobial activities [107].…”

“…Recently, a collection of dehydro-viniferin analogues were synthesized and evaluated for their antimicrobial activities [107]. Recently, a collection of dehydro-viniferin analogues were synthesized and evaluated for their antimicrobial activities [107]. A chemical-structure analysis indicated that resveratrol was a polyphenol biphenyl, and that multiple hydroxyl groups affected its biological activities as well as cisor transstructures [123][124][125].…”

Stilbenoids as Antifungals to Counteract Rice Blast Pathogen Pyricularia oryzae

“…We prepared a set of natural stilbenoids including monomers (resveratrol, pterostilbene, piceatannol, deoxyrhapontigenin, pinostilbene, and 3,4′-dimethoxy-5-hydroxystilbene) and dimers (δ-viniferin, pterostilbene, ε-viniferin, and pallidol) (Figure ) to have an overview of the natural compounds’ antifungal activity. All of these molecules were synthesized following previously reported procedures. , …”