known in lichens: acetyl-malonate pathway, shikimate pathway, and mevalonate
pathway.
4.1.1 Acetyl-Malonate Pathway
The formation of the polyketide chain could be envisaged as a series of Claisen
reactions between the starting acetyl CoA and various number of malonyl CoA since
every step ends by decarboxylation reaction. Orsellinic acid, the main intermediate
in the biosynthesis of depsides and depsidones, is formed by intramolecular aldol
reaction of the polyketide containing four keto groups and subsequent enolization
and hydrolysis. Esterification of two orsellinic acid molecules affords lecanoric acid
as member of depsides class. The most known orcinol-type depsidones have an α- or
a β-keto group in the side chain of the first ring. It is well known that this functional
group has a strong effect upon the ester linkage between the two rings since enol
lactones form readily. Oxidative cyclization of depsides to depsidones usually joins
the 2-hydroxyl of ring A and the 5-position of ring B.
C-methylation, Claisen reaction, and subsequent aromatization of the same polyketide leads to methylphloracetophenone. Radical coupling of two radicals derived
from this intermediate affords bis dienone from which usnic acid is formed.
By Claisen reaction, aromatization and subsequent cyclization reactions of the
polyketide containing five keto groups 5,7-dihydroxy-2-methylchromone are
formed as key intermediate for synthesis of chromones and xanthones.
Polyketide containing eight keto groups undergoes several aldol reactions
followed by reactions such as enolization, oxidation, decarboxylation, and selective
methylation to give parietin, member of the anthraquinone group. Classes of lichen
substances, which are derived by acetyl-malonate pathway, are depsides,
depsidones, dibenzofurans, anthraquinones, chromones, and xanthones (Fig. 5).
Depsides
Polyphenolic compounds consisting of two or more monocyclic aromatic units
linked by an ester bond are called depsides. The most common are products of
intermolecular esterification of similar or identical units. Second esterification leads
to tridepsides.
Evernic Acid
Evernic acid showed strong antioxidant, antimicrobial, and anticancer activities
(Fig. 6). Antiherbicidal activity was also reported. Kosanić et al. [39] found varying
antioxidant activity of evernic acid in free radical scavenging, superoxide anion
radical scavenging. Strong antibacterial activity was reported against Gram-positive
bacteria (Staphylococcus aureus, Bacillus subtilis, and Bacillus megaterium)
[28]. Antitumor activity of evernic acid against HeLa cancer cell lines was also
reported [40]. Evernic acid acts also as photosystem II inhibitor [41].
Lecanoric Acid
The antitumor, antioxidant, antibacterial, and antifungal activities of lichen compound lecanoric acid were confirmed (Fig. 7). Bogo et al. [42] tested cytotoxicity of
9 Lichen Metabolites: An Overview of Some Secondary Metabolites and Their. . .
183
pathway.
4.1.1 Acetyl-Malonate Pathway
The formation of the polyketide chain could be envisaged as a series of Claisen
reactions between the starting acetyl CoA and various number of malonyl CoA since
every step ends by decarboxylation reaction. Orsellinic acid, the main intermediate
in the biosynthesis of depsides and depsidones, is formed by intramolecular aldol
reaction of the polyketide containing four keto groups and subsequent enolization
and hydrolysis. Esterification of two orsellinic acid molecules affords lecanoric acid
as member of depsides class. The most known orcinol-type depsidones have an α- or
a β-keto group in the side chain of the first ring. It is well known that this functional
group has a strong effect upon the ester linkage between the two rings since enol
lactones form readily. Oxidative cyclization of depsides to depsidones usually joins
the 2-hydroxyl of ring A and the 5-position of ring B.
C-methylation, Claisen reaction, and subsequent aromatization of the same polyketide leads to methylphloracetophenone. Radical coupling of two radicals derived
from this intermediate affords bis dienone from which usnic acid is formed.
By Claisen reaction, aromatization and subsequent cyclization reactions of the
polyketide containing five keto groups 5,7-dihydroxy-2-methylchromone are
formed as key intermediate for synthesis of chromones and xanthones.
Polyketide containing eight keto groups undergoes several aldol reactions
followed by reactions such as enolization, oxidation, decarboxylation, and selective
methylation to give parietin, member of the anthraquinone group. Classes of lichen
substances, which are derived by acetyl-malonate pathway, are depsides,
depsidones, dibenzofurans, anthraquinones, chromones, and xanthones (Fig. 5).
Depsides
Polyphenolic compounds consisting of two or more monocyclic aromatic units
linked by an ester bond are called depsides. The most common are products of
intermolecular esterification of similar or identical units. Second esterification leads
to tridepsides.
Evernic Acid
Evernic acid showed strong antioxidant, antimicrobial, and anticancer activities
(Fig. 6). Antiherbicidal activity was also reported. Kosanić et al. [39] found varying
antioxidant activity of evernic acid in free radical scavenging, superoxide anion
radical scavenging. Strong antibacterial activity was reported against Gram-positive
bacteria (Staphylococcus aureus, Bacillus subtilis, and Bacillus megaterium)
[28]. Antitumor activity of evernic acid against HeLa cancer cell lines was also
reported [40]. Evernic acid acts also as photosystem II inhibitor [41].
Lecanoric Acid
The antitumor, antioxidant, antibacterial, and antifungal activities of lichen compound lecanoric acid were confirmed (Fig. 7). Bogo et al. [42] tested cytotoxicity of
9 Lichen Metabolites: An Overview of Some Secondary Metabolites and Their. . .
183