Glycosides and Glycosidic Bond Formation

• Glycosides are found in plants, animals, and microorganisms
• Glycosides play a role in metabolism, defense, and signaling

Glycosidic Bond Formation

• Glycosides are formed from a glycone (sugar component) and an aglycone (non-sugar component)
• Glycosides are acetals where the hydroxyl group of the sugar condenses with the hydroxyl group of the non-sugar
• Glycosides can be considered sugar ethers
• The sugar portion of a glycoside is the glycone
• The non-sugar portion of a glycoside is the aglycone
• Sugar molecules condense with an acceptor unit (aglycone) during Glycoside biosynthesis
• Biosynthesis occurs in two main steps

Glycoside Biosynthesis Steps

• UTP + Sugar 1-P are converted to UDP-Sugar + PPi via Uridyl transferase
• UDP – Sugar + Acceptor are converted to Acceptor – Sugar + UDP via Glycosyl transferase

Glycosides Classification by origin Pathway

• Shikimic Acid Pathway: chorismate-derived glycosides include anthraquinone, phenol and alcohol. Prephenate-derived glycosides include aldehyde, flavonoids, and lactone
• Mevalonic Acid Pathway: steroidal, triterpenoid, and cardiac glycosides
• Other glycosides: cyanophores, glucosinolates, and miscellaneous

Anthraquinone Glycosides

• Aglycone part is anthracene
• Most are cathartics except chrysarobin (ketarolytic)
• Derivatives are orange-red

Cascara Sagrada

• Anthraquinone Glycoside
• Source: Dried bark of Rhamnus purshianus, DeCandolle
• Family: Rhamnaceae
• Constituents: Cascaroides A and B (barbaloin), cascaroides C and D (chrysaloin)
• Casanthrol is a purified mixture of anthranol glycosides from Cascara sagrada
• Uses: Cathartic

Frangula or Buckthorn Bark

• Anthraquinone Glycoside
• Source: Dried rhizome Rhamnus frangula, Linné
• Family: Rhamnaceae
• Constituents: Rhem anthrones and Frangulin A and B
• Uses: Present in Movicol, as a cathartic and laxative

Aloe/Aloes

• Anthraquinone Glycoside
• Source: Dried latex of leaves of various species of Aloes, including Aloe barbadensis (Miller), A. vera (Linné), A. ferox (Miller), A. Africana (Miller) and A. spicata (Baker)
• Family: Liliaceae
• Constituents: Barbaloin (aloe-emodin) and Isobarbaloin

Rhubarb or Rheum

• Anthraquinone Glycoside
• Source: Dried rhizome and root deprived of periderm tissues of Rheum officinale (Bailon) or R. palmatum (Linné)
• Family: Polygonaceae
• Constituents: Rhem anthrones
• Uses: Cathartic preparations

Senna or Senna Leaves

• Anthraquinone Glycoside
• Source: Dried leaflet of Alexandria senna (Cassia acutifolia, Delile) or Tinnevelly senna (C. angustifolia, Vahl)
• Family: Leguminosae
• Constituents: Dimeric glycosides, sennosides A and B
• Uses: Cathartic at a usual dose of 2g

Chrysarobin or Goa

• Anthraquinone Glycoside
• Source: Obtained from lysogenous cavities in the wood of Andira araroba, Aguiar
• Family: Leguminosae
• Constituents: Chrysophenol anthrone or chrysophenol anthranol
• Uses: Keratolytic agent for psoriasis, trichophytosis, and chronic eczema treatment

Danthron or Chrysazin

• Anthraquinone Glycoside
• A 1,8-dihydroanthraquinone
• Occurs as an orange crystalline powder, practically insoluble in water but soluble in alcohol, ether, and benzene
• Uses: Cathartic drug at a usual dose of 75 – 150 mg, current use is as an antioxidant

Cyanophoric or Cyanogenic Glycosides

• Glycosides yield hydrocyanic acid (HCN) as a product and are derivatives of mandelonitrile
• Identified via the Guignard Test
• Uses: Flavoring agents, anticancer claims, possible control of sickle cell anemia

Bitter Almond

• Cyanophoric or Cyanogenic Glycoside
• Source: Prunus amygdalus
• Family: Rosaceae
• Constituents: Amygdalin
• Uses: Arthritis and BP management, maintains body pH level

Wild Cherry

• Cyanophoric or Cyanogenic Glycoside
• Source: Dried stem bark of Prunus serotina, Ehrhart and Prunus virginiana
• Family: Rosaceae
• Constituents: Prunasin
• Uses: Flavored vehicle, sedative expectorant

Apricot Pits

• Cyanophoric or Cyanogenic Glycoside
• Source: Fruit of Prunus amerniaca
• Family: Rosaceae
• Constituents: Laetrile or Vit B17
• Uses: Possibility of controlling sickle cell anemia

Cassava

• Cyanophoric or Cyanogenic Glycoside
• Source: Mannihot esculenta
• Family: Rosaceae
• Constituents: Mannihotoxin
• Uses: Food

Saponin Glycoside

• Aglycone part is sapogenin
• Toxic aglycone: sapotoxin
• Irritates mucus membranes
• Toxic to cold-blooded animals (fish poisons)
• Organic compounds that form colloidal solutions with froth when shaken with water, even in dilute solutions

Saponin Glycoside Characteristics

• Forms a persistent froth with water
• Forms a precipitate with Ba (OH)2
• Bitter and acrid taste
• Causes Hemolysis with RBC’s
• Enhances the absorption of other drugs
• Drugs containing saponin are typically sternutatory

Saponin Glycosides Biosynthesis

• Uses the Acetate – Mevalonate pathway
• Acetate and mevalonate are incorporated into spiroketal
• Forms Triterpenoid and steroidal saponins

Saponin Glycosides Qualitative Tests

• Froth test
• Liebermann – burchard test
• Hemolysis test
• Capillary test tube
• Fehling’s test

Glycyrrhiza or Licorice Root

• Triterpenoidal type Glycoside
• Source: Dried rhizome and roots of Glycyrrhiza glabra(Linné)
• Family: Leguminosae
• Constituents: Glycyrrhizin (glycyrrhizic acid)
• Uses: Demulcent and expectorant, flavoring agent, increases foaminess of beer, masks the bitter taste of drugs like Aloe, NH4Cl and quinine. used for treatment of Addison’s disease
• Contraindication: Should not be taken by patients with cardiac problems

Ginseng

• Steroidal type Glycoside
• Source: Asia (Panax ginseng) and America (Panax quinquefolius)
• Family: Araliaceae
• Constituents: Panaxosides, Ginsenosides, Chikusetsusaponins
• Uses: Aphrodisiac, treats sexual impotence, antidiabetes, insomnia and gastritis, and acts as adaptogens

Sarsapilla

• Steroidal type Glycoside
• Source: Smilax regelii
• Family: Liliaceae
• Constituents: Sarsasapogenin, smilagenin, and parilin
• Uses: Treatment of syphilis, diabetes, gastritis, skin diseases (psoriasis and eczema)

Dioscorea

• Steroidal type Glycoside
• Source: Root of Discorea spiculiflora and D. floribunda
• Family: Dioscoreaceae
• Constituents: Botogenin and disogenin
• Uses: Anti-inflammatory, diuretic, and diaphoretic

California Soap Plant

• Steroidal type Glycoside
• Source: Chlorogalum pomeridianum
• Family: Liliaceae
• Constituents: Amolonin
• Uses: Antidandruff

Isothiocyanate Glycosides

• Aglycone is Isothiocyanate
• Mostly found in Cruciferae
• Has a Mustard smell
• Use as condiments

Isothiocyanate Glycosides Biosynthesis

• Biosynthesis incorporates acetate to allyl moiety
• Aglycone portions of thioglycosides mainly consist of aliphatic or aromatic derivatives

Black Mustard/Sinapis Nigra

• Saponin Glycosides
• Source: Dried ripe seed varieties of Brassica nigra (Linné) Koch or B. juncea (Linné) Czerniaew
• Family: Cruciferae
• Constituents: Sinigrin
• Uses: Local irritant, emetic, and rubefacient

White Mustard/Sinapis Alba:

• Saponin Glycosides
• Source: Brassica alba (Linné) Hooker filius
• Family: Cruciferae
• Constituents: Sinalbin
• Uses: Diuretic and anti-inflammatory

Identifying Saponin Glycosides

• Uses Qualitative, Odor and Ferric chloride tests

Flavonol Glycosides

• Aglycone part is flavonoids
• Usually visible as yellow pigments in plants
• Mostly found in citrus plants (Rutaceae)
• Flavonoids include Rutin and Quercitin.
• Bioflavonoids include Hesperidin, Hesperitin, Diosmin and Naringen

Flavonol Glycosides Constituents

• Rutin & Hesperidin (aka Vitamin P)
• Treat capillary bleeding caused by capillary fragility
• Citrus Flavonoids can treat symptoms of common colds
• Rutin and Citrus Bioflavonoids are sometimes included in dietary supplements

Flavonol Glycosides Other Sources

• Milk Thistle (Silybum marianum); Constituents: Silibinin, Silymarin, Uses: Local irritant, emetic, rubefacient
• Ginkgo (Ginkgo biloba); Constituents: Gingkolide, Bilobalides; Uses: Memory enhancement

Alcohol Glycosides

• Detected by ester formation, C2H5-OH + CH3COOH resulting in CH3COOC2H5
• Salicin is hydrolyzed into D-glucose and saligenin (salicyl alcohol) by emulsin
• Possess Anti-rheumatic properties

Willow Tree

• Alcohol Glycosides
• Source: Salix purpurea and Salix fragilis
• Family: Salicaceae
• Constituents: Salicin
• Uses: Antirheumatic and anti-inflammatory

Aldehyde Glycosides

• Aglycone part is Vanillin (methyl protocatechuic aldehyde)

Aldehyde Glycosides Biosynthesis

• The conversion of cinnamic acid to vanillin is the most probable route, uses the Shikimic pathway

Vanilla or Vanilla Bean

• Aldehyde Glycosides
• Source: Cured, full-grown, unripe fruit of Vanilla plantifolia (Andrews)(Mexican or Bourbon vanilla) and Vanilla tahitensis, J.W. Moore (Tahita vanilla)
• Family: Orchidaceae
• Constituents: Vanillin
• Uses: Flavoring agent and pharmaceutic aid

Lactone Glycosides

• Coumarin glycosides that contain Lactones
• Include Viburnum prunifolium and V. opolus, which have antispasmodic properties attributed to scopoletin and may act as uterine-sedatives
• Other Lactone Glycosides: Cantharidin and methoxsalen (dermatological use), and Santonin (from the unexpanded flowerheads of Artemisia cina), which is formerly used as an anthelmintic (potential toxicity)

Coumarin

• Lactone Glycoside
• Source: Tonka beans (Dipteryx odorata), sweet clover (Melilotus albus), Medicus and M.officinalis (Linné), Lamarck, red clover (Trifolium pratense, Linné )
• Family: Leguminaceae
• Uses: Antithrombotic, anticoagulant, and flavoring agent (banned by the US FDA)

Dicumarol

• Lactone Glycoside
• Source: Cured leaves and flowering tops of Melilotus officinalis (Linné), red clover (Trifolium pratense Linné))
• Family: Leguminaceae
• Uses: Anticoagulant, with a usual dose 25 to 200 mg OD as indicated by prothrombin time

Cantharides

• Lactone Glycoside
• Consists of dried Spanish flies, Russian flies or Blistering flies (the insect Cantharis vesicatoria (Linné) De Geer)
• Family: Meliodae
• Constituents: Cantharidin
• Uses: Irritant, vesicant, wart removal and rubefacient
• Caution: priaprism if taken internally

Psoralens

• Lactone Glycoside
• Photosensitizing furocoumarins
• Source: Cremocarps of Bishop's flower (Ammi majus, Linné)
• Family: Umbelliferae
• Constituents: Methoxsalen and 8-methoxypsoralens, or xanthotoxin
• Uses: Facilitate repigmentation in idiopathic vitiligo & psoriasis
• Contraindication: Keep patients away from sun

Phenol Glycosides

• The aglycone groups of many of the naturally occurring glycosides are phenolic
• Drugs yield glucose + hydroquinone
• Millon’s test produces (+) peach/salmon/pink coloration with the mercury complex of the nitrophenyl derivative

Uva Ursi

• Phenol Glycosides
• Source: Dried leaf of Bearberry (Arctostaphylos uva-ursi (Linné) Sprengel)
• Family: Ericacea
• Constituents: Arbutin
• Uses: Astringent, diuretic and whitening agent

Gaultherin

• Phenol Glycosides
• Source: Gaultheria procumben (Linné) (Wintergreen)
• Family: Ericacea
• Constituents: Gaultherin
• Uses: Use in candies and as a spice, for rheumatism, and for sore muscles