## 3 Coumarins in the Context of Phenolic Composition
Dicoumarol, and related compounds with substituent groups (R) on carbon atoms at 3, 5, 6, 7 and 8-positions, are often addressed due to their unique molecular structures, which may include two intramolecular O-H-O hydrogen bonds (Figure 13b) and different biological features, depending on the type of substituents on the central methylene linkage (3-position). The parent molecule, the 4-hydroxycoumarin, which may be represented as one of three tautomeric structures (Figure 14), effectively depicts the structural changes occurring in dicoumarol. Some studies have shown that coumarin form A (Figure 14) is the primary tautomer in both the solid state and in solution in polar solvents [109; 110], which is relevant in the context of spirit beverages. In general, nature exhibits a certain degree of creativity; given the proper building blocks, it is capable of producing the most varied compounds, and bicoumarins are an  
Figure 14: Tautomeric structures of 4-hydroxycoumarin (**A–C**). Figure 12: Schematic illustration of the phenylpropanol pathway leading to coumarins (particularly aesculetin and scopoletin) and the formation of flavonoids and other phenolic compounds. PAL: l-phenylalanine ammonia-lyase. Figure 13: Structures of dicoumarol without (**a**) and with (**b**) intramolecular O–H–O hydrogen bonds. example of this feature. A wide variety of bicourarins are available, each of which is composed of coumarins connected by carbon-carbon bonds or an ether linkage. Nevertheless, these links are located on different carbon atoms, such as C3-C3\({}^{\prime}\), C3-C6\({}^{\prime}\), C3-C7, C3-C8\({}^{\prime}\), C4-C4\({}^{\prime}\), C8-C8\({}^{\prime}\), C5-C6\({}^{\prime}\), C6-C6, C6-C8\({}^{\prime}\), C5-C8\({}^{\prime}\), C7-C7\({}^{\prime}\), C7-C8\({}^{\prime}\), C8-C8\({}^{\prime}\), or C6-C6\({}^{\prime}\)-linked bicourarins. Spirobicourarins, monoterpene-unit-linked bicourarins, and C3-C3\({}^{\prime}\)- linked with methylene and methine group-linked bicourarins are further examples of bicourarin sets [105]. Being aware of the metabolic pathways of compounds such as coumarins is useful for a variety of reasons, including nutraceuticaltical and safety evaluations (detailed in Sections 7 and 8). Determining how coumarins are metabolised can be useful for identifying the risks associated with their consumption and defining safe levels of exposure. In terms of coumarin metabolism, two major processes have been identified: 7-hydroxylation (umbelliferone) and the opening of the lactone ring with the loss of carbon dioxide (Figure 15). This reaction takes place on the intermediate coumarin 3_A_-epoxide produced in phase I of the metabolic process. Under aqueous conditions, this epoxide releases carbon dioxide to create _ortho_-hydroxyphenyl acetaldehyde (_o_-HPA), which can subsequently be metabolised to the corresponding acid (_o_-HPAA) and alcohol (_o_-HPE). A series of intermediates can be formed when glutathione nucleophilically attacks the 3_A_-epoxide, including the 4-HDHC-GSH (4-hydroxy-3,4-dihydrocomarin-3-mercapquric acid) or 3-hydroxycoumarin. Understanding coumarins' metabolic pathways is crucial for determining the toxicity of the metabolites generated through excretion, as well as for extrapolating the formation of coumarins in spirit beverages through various chemical processes such as oxidation, reduction, hydroxylation, radical reactions, electrophilic or nucleophilic additions, and metal-catalysed additions (mainly copper and iron) [28; 114; 115; 116]. These processes may occur during the prolonged ageing of beverages in wooden barrels and may cause changes in the coumarin profile. Figure 15: Illustrative routes of coumarin metabolism (adapted from [111; 112; 113]). GSH: glutathione.