Natural Organic Acid as Green Catalyst for Xanthenones Synthesis: Methodology, Mechanism and Calcium Channel Blocking Activity

Bruna Terra,Felipe Martins,Cameron Da Silva,Daniella Bonaventura,Luciene Vieira,Natália De Araújo,Andressa Mouro,Antonio Alcântara,Ângelo De Fátima,Heitor De Abreu,Rebeca Santos,Aura Osorio,Aline De Oliveira

doi:10.21577/0103-5053.20170082

Bruna Terra, Felipe Martins + Show 11 more

Open Access

https://doi.org/10.21577/0103-5053.20170082

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Abstract

Xanthenones were synthesized via one-pot tricomponent reaction, under solvent-free conditions, using aldehydes, phenolic and cyclic 1,3-dicarbonyl compounds. Natural organic acids (NOAs), compounds present in many living metabolisms, were used as potential green catalysts. NOA are considered to be more eco-friendly and user-friendly alternative to traditional methodologies. Optimization studies showed that oxalic acid was the best NOA catalyst for such reaction furnishing the xanthenones with up to 93% of yield. Theoretical calculations were performed to evaluate this reaction mechanism and regioselectivity. The results showed that the regiospecificity of this three-component reaction is kinetically and thermodynamically controlled by the addition of β-naphthol C2, instead of C10, to the aldehyde. Our results also disclosed two xanthenones as novel calcium channels blockers. Eco-friendly reaction conditions, easy workup procedure, short reaction times and good yields are some of the advantages of our methodology.

Highlights

Xanthones (Figure 1) are a class of oxygenated heterocycles that contain an aromatic ring fused to 4-carbonyl-pyran ring as the basic skeleton.[1]
The evaluated organic acids follow a homologous series in which the number of carbons between the carboxyl groups varies; the oxalic having no carbon among them; the malonic acid has one carbon; the succinic acid has two carbons and the acetic acid is the corresponding monocarboxylic acid
The pKa1 value of dicarboxylic acids increases with the increase in the number of carbons between the carboxylates; a fact that can be explained by the inductive effect of the neighboring carboxyl and the stability of the corresponding conjugated base

Summary

Introduction

Xanthones (Figure 1) are a class of oxygenated heterocycles that contain an aromatic ring fused to 4-carbonyl-pyran ring as the basic skeleton.[1] They present several biological and pharmacologic properties: antivascular, antiarrhythmic, antihypertensive, antioxidant, anti-inflammatory, anticancer and calcium channel blocking.[2] On the other hand, xanthenones (Figure 1), xanthone derivatives, are poorly explored regarding their biological properties, and described only for its anti‐proliferative,[3,4] antiviral[5] and anti-microbial properties.[6]. The literature describes the synthesis of xanthenones via a multicomponent reaction using a phenolic compound, an aldehyde, and a cyclic 1,3-dicarbonyl compound.[7] Many Lewis or Brönsted acids may be used as catalysts: calixarenes,[3]. Natural Organic Acid as Green Catalyst for Xanthenones Synthesis

Methods

Results

Conclusion