2.3.2 Hydroxycoumarins
Hydroxycoumarins are invariably found in a large number of plant families. However, the relatively more common ones are based upon the following substances, such as: umbelliferone (7-hydroxy coumarin), aesculetin (6, 7-dihydroxy-coumarin) and scopoletin (6-methoxy-7-hydroxy coumarin) as given below.
Interestingly, some rarer hydroxycoumarins are, namely, dephentin (7, 8-dihydroxy coumarin) and fraxetin (6-methoxy, 7-8-dihydroxy coumarin) are both obtained from plant sources.
A few typical examples of hydroxycoumarins shall be described in the sections that follow, e.g., Umbelliferone, Esculetin, and Scopoletin.
2.3.2.1 Umbelliferone
Synonyms Hydrangin; Skimmetin.
Biological Sources Umbelliferone is present in a variety of medicinal plants, for instance: Apium graveolens L. (Apiaceae) Celery; Artemisia abrotanum L. (Asteraceae)-Southernwood, Old Man; Daphne mezereum L. (Thymelaeaceae)-Mezereon; Dipteryx odorata (Aubl.) Willd. (Fabaceae)-Tonka Bean, Tonga, Cumaru; Ferula sumbul Hook. (Apiaceae)-Sumbul, Mask Root; Hydrangea paniculata Seib. (Saxifragaceae)-Peegee; Lavandule angustifolia Mill. (Lamiaceae)-Lavender; Matricaria chamomilla L. (Asteraceae)-Hungarian Camomile, German Camomile, Manzanilla; and Pimpinella anisum L. (Apiaceae)-Anise.
Preparation Asafoetida contains resin (40-65%) which consits of chiefly a resin-alcohol asaresinotannol both in the free or combined form with ferulic acid, and of course, free umbelliferoneis totally absent in the drug. Thus, umbelliferone is prepared by treating ferulic acid with HCl which gets converted to umbellic acid and the latter loses a molecule of water to give rise to umbelliferone as given below:
Umbelliferone may also be obtained by distillation of resin from Umbelliferae.*
Characteristic Features It is obtained as needles from water. It develops the characteristic odour of coumarin on heating. Its mp is 225-228°C. It usually sublimes. Its solubility in water is very poor i.e., it dissolves 1 g in nearly 100 ml of boiling water. It is freely soluble in ethanol, chloroform, acetic acid and dilute alkaline solution. It is sparingly soluble in ether and the solutions exhibit a distinct blue fluorescence.
Identification Test When 0.5 g of umbelliferone is triturated with pure sand (SiO2) and 5 ml of HCl, added 5 ml of water, filtered and to the filtrate added an equal volume of ammonia solution, it gives a beautiful blue fluorescence.
Uses
1. It is an important ingredient in most sunscreen lotions and creams.
2. It is most importantly used as an intracellular and pH sensitive fluorescent indicator and bloodbrain-barrier (BBB) probe.
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* Z wenger, Ann., 115, 1, 15 (1860).
2.3.2.2 Esculetin
Synonyms Aesculetin; Chicorigenin; 6, 7-Dihydroxy-coumarin.
Biological Source It is the aglucon of esculin and cichorlin: Esculin is derived from two different plant sources, namely: (a) the barks of Crataegus oxycantha L. (Rosaceae)-Hawthorn; and (b) the flowers of Centarea cyanus Linn., (Compositae). It is a glucoside which upon hydrolysis gives the aglucon esculetin.
Esculetin is also obtained from cichorlin, which is a glucoside and found to be isomeric with esculin. Cichorlin is present in the flowers of the chicory plant (Chichorium intybus L., family: Compositae).
Preparation It is obtained by the hydrolysis of the following two glucosides, namely:
(a) From Esculin:
(b) From Cichorlin:
Characteristic Features It is obtained as prisms from glacial acetic acid and as leaflets by vacuum sublimation. Its mp is 268-270°C. It is soluble in dilute alkalies (2M solution) with the emission of blue fluorescence. It is almost insoluble in ether and in boiling water, but moderately soluble in hot ethanol and in glacial acetic acid.
Uses It is mostly in filters for absorption of uv-light
2.3.2.3 Scopoletin
Synonyms Chrysatropic acid; Gelseminic acid; 6-Methoxyumbelliferone; β-Methylesculetin; 7-Hydroxy 6-methoxycoumarin.
Biological Sources It is the aglucone of scopolin. Scopoletin occurs in the roots of Arnica montana L. (Asteraceae)-Mountain Tobacco, Leopard’s-bane; leaves of Artemesia abrotanum L. (Asteraceae)-Southernwood, Old Man; roots and leaves of Atropa belladona L. (Solanaceae)-Belladonna, Deadly Nightshade; barks of Brunfelsia uniflorus (Phol.) D. Don. (Solanaceae)-Manaca, Manacan; fruits of Capsicum annuum L. (Solanaceae)-Chili, Sweet Peppers, Paprika; oil of the plant Chamaemelum nobile (L.) All. (Asteraceae)-Roman Comomile; English Camomile, Comomile; and roots of Withania somniferum (L.) Dunal (Solanaceae)-Ashwagandha.
Preparation It is obtained by the hydrolysis of the glucoside scopolin i.e., 7-(β-D glucopyranosyloxy)-6-methoxy-2H-1-benzopyran-2-one as follows:
Characteristic Features Scopoletin occurs as prisms or needles from either acetic acid or chloroform. It melts at 204°C and has a uvmax: 230, 254, 260, 298, 346 nm (log ε 4.11, 3.68, 3.63, 3.68, 4.07). It is slightly soluble in water or cold ethanol and quite soluble in hot ethanol and hot glacial acetic acid. It is moderately soluble in chloroform, but practically insoluble in the non-polar solvent benzene.
Identification Tests
1. Dissolve 0.1 g in ethanol and warm it in an electric water-bath to affect dissolution. The resulting solution gives a blue fluorescence.
2. A solution of 0.1 g in 3 ml of hot ethanol reduces the Fehling’s solution thereby leaving behind a brick-red precipitate of cupric oxide (CuO).
It is pertinent to mention here that there exists some rarer species of hydroxycoumarins, such as: daphentin and fraxetin, which shall now be discussed in the sections that follows:
2.3.2.4 Daphentin
Synonyms 7, 8-Dihydroxycoumarin;
Biological Sources It is the aglucon of daphnin. It is obtained from the seeds and fruits of Daphne mezereum L. (Thymelaeaceae)-Mezereon; and the seeds of Euphorbia lathyris L. (Euphorbiaceae)-Mole Plant, Petroleum Plant, Caper Spurge.
Preparation Daphentin is prepared conveniently from its glucoside known as daphnin i.e., 7, 8-dihydroxycoumarin 7-β-D-glucoside by treating the latter in three different ways, namely: (i) By boiling with dilute mineral acids; (ii) By enzymatic hydrolysis; and (iii) By sublimation as given below:
Characteristic Features The crystals obtained from dilute ethanol has a mp 256°C (decomposes). It undergoes sublimation on heating. It is soluble in boiling water, hot dilute alcohol and hot glacial acetic acid. It is found to be sparingly soluble in ether, CS2, chloroform, and benzene.
Identification Tests
1. An aqueous solution of daphentin gives a green colouration with FeCl3 solution, which turns red on the addition of sodium carbonate.
2. An alkaline solution of daphentin in alkali carbonate or alkali gives a yellow colour.
2.3.2.5 Fraxetin
Synonyms 7, 8-Dihydroxy-6-methoxycoumarin.
Biological Source It is the aglucon of fraxin. Fraxin is present in the seeds of Acsculus hippocastanum L. (Hippocastanaceae)-Horse Chestnut.
Preparation Fraxetin is obtained by heating fraxin with dilute sulphuric acid to affect the hydrolysis of glucoside and get the desired aglucon residue as shown here under:
Characteristic Features Fraxetin is obtained as plates from ethanol having mp 228°C. It has been observed that it turns first yellow at 150°C and subsequently brown at mp. It is soluble in 10 L of cold water, but in 300 ml of boiling water. It is somewhat more soluble in alcohol and practically insoluble in ether.
Identification Tests It forms the corresponding dimethyl ether termed as 6,7,8-trimethoxycoumarin (C12H12O5) which has a mp 104°C and bp0.2 90-100°C.
