Phenolic Glycosides

lec.( 6 )

phenols / phenolic glycosides

these chemical structures are classified by the presence of a benzenering combined with an alcohol. most members of this class of compounds have antiseptic activity and are also anthelmintic and caustic. in order for the body to absorb this compound, they are usually naturally combined with a sugar to form a glycoside.
a familiar example of this compound is salicylic acid, which is found free or as methyl salicilyte in many plants such as meadowsweet and willow. this is the basis of aspirin and a whole class of non-steriodal anti-inflammatory drugs (nsaids). it is here that may best show how the chemical may have a whole range of properties that are not necessarily those of the plant. salicylates are well known to cause severe stomach irritation, even leading to stomach hemorrhage. however, in a plant such as meadowsweet, the whole remedy can actually stop bleeding in the stomach. it is thus important to realize that the actions of a whole plant cannot always be predicted by knowledge of their constituents.
other actions related to this class of compounds includefever reduction, general anti-inflammatory effect, increased volume and concentration of bile, and rubefacient actions when used externally. it is now known that this anti-inflammatory effect is due to an anti-prostaglandin and bradykinin action, which would also explain the use of salicylates as anti-blood-clotting agents. in summary, these are generally useful compounds that are quite safe when used in their natural plant context. two other familiar examples are eugenol from cloves, which helps tooth aches, and thymol from thyme and other aromatic remedies which is a useful anti-septic and anti-fungal oil.
phenolic group of glycosides:-
here the aglycone is a simple phenolic structure. an example is arbutin.
arbutin,which isolated from commonbearberry leaves
arctostaphylosuva-ursiis an example of phenolic glycoside (simple). rutin is present in rooibos tea.phenolic glycosides (simple) possess antiseptic properties that are useful for the health of the urinary tract.
. it has a urinary antiseptic effect.

uses: uti as antiseptic and antibacterial & mild diuretic


drugs :
-esoterica :cream :age spots
-hydroquinone solution : wet hands



lactone glycosides


•coumarin•classified as a simple phenylpropanoid•occurs in
tonka beans, sweet vanilagrass(anthoxanthumodoratum fam
poaceae),sweet clover (melilotusalbus/officinalis
fabaceae) etc.•formerly used as flavoring agent, fdabanned the use of coumarin and coumarincontaining materials as flavoring agent(con’t)

cantharide zoological origin: cantharis vesicatoria
part used: dried insects
collection: insects are collected during month of june an july in early morning when these are sluggish and inactive. insects are killed by exposing them to fumes of ammonia, hydrogen sulfide, carbon disulfide or acetic acid . insects are dried in an oven at temperature not exceeding 40°c and packed in air tight container with few dropings of chloroform or carbon tetra chloride.
chemistry: active principle is cantharidin. in addition to this, it contains formic acid acetic acid fat fixed oil uric acid
uses: counter irritant vesicant rubefacient
lactoneglycosides:

–bishydroxycoumarin (dicumarol) is obtainedfrom improperly cured leaves andflowering tops of
melilotus officinalis

(fabaceae) –
anti -coagulant property
(determine byaptt) as prophylaxis and treatment of venousthrombosis and pulmonary embolism –interfere with vit. k action



coumarins

the sweet-smelling plant substance called coumarin. for the anticoagulant rodenticide poisons often called "coumarins" or "coumadins", see 4-hydroxycoumarins.

coumarin



iupac name[hide]
2h-chromen-2-one
other names[hide]
1-benzopyran-2-one
identifiers



















coumarin : (2h-chromen-2-one) is a fragrant organic chemical compound in the benzopyrone chemical class, which is a colorless crystalline substance in its standard state. it is found naturally in many plants, notably in high concentration in the tonka bean (dipteryxodorata), vanilla grass (anthoxanthumodoratum), sweet woodruff (galiumdoratum), mullein (verbascum spp.), sweet grass (hierochloeodorata), cassia cinnamon (cinnamomumaromaticum), melilot (melilotus ssp.), deers tongue (panicumclandestinum) and sweet clover (fabaceae spp.). the name comes from a french word, coumarou, for the tonka bean. it has a sweet odor, readily recognised as the scent of new-mown hay, and has been used in perfumes since 1882. sweet woodruff, sweet grass and sweet clover in particular are named for their sweet smell, which in turn is due to their high content of this substance. when it occurs in high concentrations in forage plants, coumarin is a somewhat bitter-tasting appetite suppressant, and is presumed to be produced by plants as a defense chemical in order to discourage predation.
coumarin has been used as an aroma enhancer in pipe tobaccos and certain alcoholic drinks, although in general it is banned as a flavorant food additive, due to concerns about coumarin s hepatotoxicity in animal models.

although coumarin itself has no anticoagulant properties, it is transformed into the natural anticoagulant dicoumarol by a number of species of fungi. this occurs as the result of the production of 4-hydroxycoumarin, then further (in the presence of naturally occurring formaldehyde) into the actual anticoagulant dicoumarol, a fermentation product and mycotoxin. this substance was responsible for the bleeding disease known historically as "sweet clover disease" in cattle eating moldy sweet clover silage.[1]
coumarin is used in the pharmaceutical industry as a precursor molecule in the synthesis of a number of synthetic anticoagulant pharmaceuticals similar to dicoumarol, the notable ones being warfarin (tradenamed "coumadin," not to be confused with coumarin) and some even more potent rodenticides that work by the same anticoagulant mechanism. see 4-hydroxycoumarin and the relevant section of vitamin k antagonists for a discussion and listing of this class of drugs. all of these agents were historically discovered by analyzing sweet clover disease.
coumarin has clinical medical value by itself, as an edema modifier. coumarin and other benzopyrones, such as 5,6benzopyrone, 1,2 benzopyrone,diosmin, and others, are known to stimulate macrophages to degrade extracellular albumen, allowing faster resorption of edematous fluids. other biological activities that may lead to other medical uses have been suggested, with varying degrees of evidence.
coumarin is also used as a gain medium in some dye lasers, and as a sensitizer in older photovoltaic technologies.

biological function
coumarin has appetite-suppressing properties, suggesting one reason for its widespread occurrence in plants, especially grasses and clovers, is because of its effect of reducing the impact of grazing animals on these forages. although the compound has a pleasant sweet odor and is responsible for the names of sweet clover and sweet grass, these plants are not named for their taste. coumarin has a bitter taste, and animals will avoid it, if possible.
derivatives
coumarin and its derivatives are all considered phenylpropanoids.
some naturally occurring coumarin derivatives include umbelliferone (7-hydroxycoumarin), aesculetin (6,7-dihydroxycoumarin), herniarin (7-methoxycoumarin), psoralen and imperatorin.
4-phenylcoumarin is the backbone of the neoflavones, a type of neoflavonoids.
medical use
coumarins have shown some evidence of many biological activities, although they are approved for few medical uses as pharmaceuticals. the activity reported for coumarin and coumarins includes anti-hiv, anti-tumor, anti-hypertension, anti-arrhythmia, anti-inflammatory, anti-osteoporosis, antiseptic, and analgesic (pain relief). it is also used in the treatment of asthma. coumarin has been used in the treatment of lymphedema.

toxicity and use in foods, beverages, cosmetics and tobacco
coumarin is moderately toxic to the liver and kidneys, with a "median lethal dose" (ld50) of 275 mg/kg — low compared to related compounds. although only somewhat dangerous to humans, coumarin is a potent rodenticide: rats and other rodents metabolize it largely to 3,4-coumarin epoxide, a toxic compound that can cause internal hemorrhage and death. humans metabolize it largely to 7-hydroxycoumarin, a compound of lower toxicity. the german federal institute for risk assessment has established a "tolerable daily intake" (tdi) of 0.1 mg coumarin per kg body weight, but also advises, [if] this level is exceeded for a short time only, there is no threat to health. for example, a person weighing 60 kg (about 132 lbs) would have a tdi of approximately 6.0 mg of coumarin. the u.s. occupational safety and health administration (osha) regardscoumarin to be not classifiable as to its carcinogenicity to humans.
european health agencies have warned against consuming high amounts of cassia bark, one of the four species of cinnamon, because of its coumarin content. according to the german federal institute for risk assessment (bfr), 1 kg of (cassia) cinnamon powder contains approximately 2.1 to 4.4 g of coumarin. powdered cassia cinnamon weighs 0.56 g/cc therefore, 1 kg of cassia cinnamon powder is equal to 362.29 teaspoons (1000 g divided by 0.56 g/cc multiplied by 0.20288 tsp/cc). this means 1 teaspoon of cinnamon powder contains 5.8 to 12.1 mg of coumarin, which may be above the tolerable daily intake for smaller individuals. however, the bfr only cautions against high daily intakes of foods containing coumarin. its report specifically states that "ceylon" cinnamon, cinnamomumverum, contains hardly any coumarin. chamomile, a common herbal tea, also contains coumarin.
coumarin is often found in artificial vanilla substitutes, despite having been banned as a food additive in numerous countries since the mid-20th century. coumarin was banned as a food additive in the united states in 1954, largely because of hepatotoxicity results in rodents. the u.s. osha considers this compound to be only a lung-specific carcinogen and "not classifiable as to its carcinogenicity to humans". coumarin was banned as an adulterant in cigarettes by tobacco companies in 1997, but due to the lack of reporting requirements to the usdepartment of health and human services it was still being used as a flavoring additive in pipe tobacco
coumarin is currently listed by the united states food and drug administration (fda) among "substances generally prohibited from direct addition or use as human food", according to 21 cfr 189.130, but some natural additives containing coumarin, such as sweet woodruff (galiumodoratum) due to its coumarin odor, are allowed "in alcoholic beverages only" (21 cfr 172.510). in europe, such beverages are very popular, for examplemaiwein (white wine with woodruff) and ?ubr?wka (vodka flavoured with bison grass). however, the coumarin content of these drinks is said to cause headaches.
coumarin is subject to restrictions on its use in perfumery as some people may become sensitised to it, however the evidence that coumarin can cause an allergic reaction in humans is disputed.
coumarin is still used as a legal flavorant in the tobacco industry, particularly for sweet pipe tobacco. its presence in cigarette tobacco led former brown & williamson executive jeffrey wigandto contact cbs news show 60 minutes in 1995, charging that there was a “form of rat poison” in the tobacco. he held that from a chemist’s point of view, coumarin is an “immediate precursor” to the rodenticide coumadin. dr. wigand later stated that coumarin itself is dangerous, pointing out that the fda had banned its addition to human food in 1954. under his later testimony he would repeatedly classify coumarin as a "lung-specific carcinogen". in germany, coumarin is banned as additive in tobacco.




chromones

chromone

iupac name[hide]
chromen-4-one















chromone (or 1,4-benzopyrone) is a derivative of benzopyran with a substituted keto group on the pyran ring. it is an isomer of coumarin.
derivatives of chromone are collectively known as chromones. most, though not all, chromones are also phenylpropanoids.

examples
6,7-dimethoxy-2,3-dihydrochromone has been isolated from sarcolobusglobosus.
eucryphin, a chromonerhamnoside, can be isolated from the bark of eucryphiacordifolia.[1]
roger altounyan studied chromones and eventually found disodium cromoglicate.[2] this drug was found to inhibit antigen challenge as well as stress induced symptoms. cromoglicate is used as a mast cell stabilizer in allergic rhinitis, asthma and allergic conjunctivitis. comparatively free of side-effects, unfortunately its short half-life limited its value.
nedocromil sodium was found to have a somewhat longer half-life.

professor dr. saad ali ihsan
ph.d. in pharmacognosy& medicinal plants