Flavonoids: hemisynthesis, reactivity, characterization and free radical scavenging activity

Abstract

Phenolic compounds form one of the main classes of secondary metabolites. They display a large range of structures and they are responsible for the major organoleptic characteristics of plant-derived-foods and beverages, particularly color and taste properties and they also contribute to the nutritional qualities of fruits and vegetables. Phenolic compounds are also highly unstable compounds which undergo numerous enzymatic and chemical reactions during postharvest food storage and processing thus adding to the complexity of plant polyphenol composition. Among these compounds flavonoids constitute one of the most ubiquitous groups of all plant phenolics. Owing to their importance in food organoleptic properties and in human health, a better understanding of their structures, their reactivity and chemical properties in addition to the mechanisms generating them appears essential to predict and control food quality. The purpose of this work is an overview of our findings concerning the hemisynthesis, the reactivity and the enzymatic oxidation of some flavonoids and shed light on the mechanisms involved in some of these processes and the structures of the resulting products. The free radical scavenging activity of some of the synthesized compounds is also presented and a structure-activity relationship is discussed. The first part of this review concerns the synthesis and structural characterization of modified monomeric flavanols. The use of these compounds as precursor for the preparation of natural and modified dimeric procyanidin derivatives was then explored through different coupling reactions. The full characterization of the synthesized compounds was achieved by concerted use of NMR and ESI-MS techniques. The free radical scavenging activity of some of the synthesized compounds was investigated. The second part of this review concerns the enzymatic oxidation of several flavonols by Trametes versicolor laccase. Most of the major oxidation products have been isolated as pure compounds and their structures unambiguously established through spectroscopic methods. Correlation between the structure of the oxidation product and the substitution pattern of the starting materials allows mechanistic features of this transformation to be elucidated.

Figure 1

Structures of flavan-3-ol monomers (1a-1d) and oligo/polymers (2).

Figure 2

Structures of the studied modified flavan-3-ol monomers 3-9.

Scheme 1

Synthesis pathways of the studied modified flavanol monomers.

Figure 3

Main fragmentations observed in compounds 11, 16 and 18 and main ¹H-¹³C long range correlations observed for compound 16.

Scheme 2

Synthesis of the activated catechin derivatives.

Scheme 3

Synthesis of 4-activated catechin through DDQ oxidation and in presence of H₂O.

Figure 4

Main fragmentations observed in compounds 20a, 20b and 20c.

Scheme 4

TiCl₄-catalyzed flavanols coupling reactions.

Figure 5

Main fragmentations observed and main ¹H-¹³C long range correlations observed in compound 24.

Figure 6

Extracted ion chromatogram recorded at m/z 1395 and main fragmentations observed in compound 25.

Scheme 5

Flavan-3-ol coupling reactions using taxifolin (9) as starting material.

Figure 7

Mass spectrum and main fragmentations observed in compound 33.

Figure 8

Structures of the flavonoids studied in the enzymatic oxidation. The structures of the obtained oxidized compounds are also shown.

Figure 9

General oxidation pathways for flavonols.

Figure 10

HMBC correlations observed for compound 45a.

Scheme 6

Postulated oxidation mechanism for compounds 36 and 37.

Figure 11

¹H-NMR spectrum of 49 (exchangeable protons are not shown).

Scheme 7

Postulated oxidation mechanism for compound 38.

Figure 12

Chromatographic profiles of the oxidation reaction mixture at 3 hours of 38 (a) and 49 (b).

Figure 13

Free radical scavenging activity of the studied compounds. The results represent the decrease (%) of the initial DPPH^• absorption at 517 nm.

Figure 14

Free radical scavenging activity of the studied compounds. The results represent the concentration IC₅₀ needed to decrease by 50% the initial DPPH^• absorption at 517 nm.