Pharmacognosy Pt 1

Page 1

• Introduction to Pharmacognosy

Page 2

• Etymology and meaning:

  • pharmacognosy from Greek: "pharmakon" = drugs; "gnosis" = knowledge or "gignosco" = to acquire knowledge

  • Literally: knowledge of drugs or pharmaceuticals

• Scope and history:

  • Part of healing arts and sciences since mankind began treating illnesses

  • Defined as the science of natural drugs and other natural products affecting health of humans and animals

Page 3

• Pharmacognosy as an applied science involves three broad facets:

  • Biological: taxonomy, morphology, anatomy, physiology, genetics, biochemistry, etc.

  • Chemical: isolation, purification, and characterization of active constituents

  • Economic: commercial production and trade of natural drugs and their constituents

Page 4

• Flückiger’s comprehensive scope: “It is the simultaneous application of various scientific disciplines with the object of acquiring knowledge of drugs from every point of view.”

Page 5

• Plant chemistry vs phytochemistry:

  • Plant Chemistry: study of plant constituents; part of natural product and organic chemistry; includes biosynthesis explaining how plants synthesize constituents from simple molecules

  • Phytochemistry: study of composition of plant principles with their extraction, biosynthesis, and identification

• Scheele: father of modern Plant Chemistry

Page 6

• Early days:

  • Western pharmacology knowledge compiled as materia medica (medical matter)

• Early 19th century shifts:

  • As knowledge grew, materia medica divided into: (1) Pharmacology and (2) Pharmacognosy (with lesser emphasis on actions)

Page 7

• Late 19th century developments:

  • Chemists synthesized numerous organic compounds; three basic drug-related disciplines emerged:

  1. Pharmacology – drug actions

  2. Pharmacognosy – information on drugs from natural sources

  3. Medicinal chemistry – synthetic drugs

Page 8

• Crude drugs:

  • Vegetable/animal drugs consisting of natural substances that have undergone only collection and drying

  • In natural product terms, a product not yet processed by shredding, grinding, crushing, distilling, extracting, or adulteration beyond essential packing for storage

Page 9

• Natural substances (categories):
  1) Whole plants/herbs and anatomical parts, saps, extracts, secretions, and other constituents
  2) Whole animals/anatomic parts, glands/organs, extracts, secretions, and other constituents
  3) Substances in their natural molecular structure (unmodified)

Page 10

• Pharmaceutically, Biological Drugs may be:
  1) Crude drugs – examples: chondrus, cascara sagrada, cochineal, thyroid
  2) Drug Constituents – chief constituents and derivatives from biologic origin or prepared synthetically or semi-synthetically – examples: ext{sucrose}, ext{menthol}, ext{progesterone}

Page 11

• Other Natural Products:
  3.1. Plant juices, exudates, secretions, extracts – examples: aloe, acacia, orange oil
  3.2. Animal secretions and extracts – examples: gelatin, chymotrypsin
  3.3. Microbial extracts and products – examples: sutilains, xanthan gum

Page 12

• Biologics:
  4.1. Antigenic matter or antibody preparations capable of developing immunity – examples: vaccines, toxoids, antitoxins, anti-rabies serum
  4.2. Diagnostic aids – examples: mumps skin test antigen, tuberculin
  4.3. Biologics related to human blood – examples: blood grouping serum, whole blood, human albumin

Page 13

• Materia medica: medical/m medicinal substances; information on drug usage

• De Materia Medica: famous 5-volume treatise by Pedanios Dioscorides; covered ~600 plant drugs plus animal/mineral products; remained authority for ~15 centuries

Page 14

• Pedanios Dioscorides – wrote “De Materia Medica” (77–78 CE) describing ~600 plants; still cited examples: belladonna, ergot, colchicum, aloe, hyoscyamus, opium

• J.A. Schmidt – first to introduce the word pharmacognosy in the title “Lehrbuch der Materia Medica”

• C.A. Seydler – first to coin the word Pharmacognosy in “Analectica Pharmacognostica”

Page 15

• Galen – Greek pharmacist-physician; described preparation methods (galenical preparations); father of Galenical Pharmacy

• Pen-ts’ao kang mu – Chinese drug encyclopedia; Li Shih-Chen; published 1596 CE; listed >2000 natural drugs

• Vedas of India – pre-1000 BCE; included >1000 healing herbs

Page 16

• Egyptian Papyrus Ebers (1550 BCE): 110 pages, long scroll; collection kept at University of Leipzig

• Pseudopharmacognostic writings – lay authors writing about natural drugs intended for lay readers

Page 17

• Drugs can be used crude or after extraction to active constituents

• Methods of extraction/separation:
  a) maceration
  b) infusion
  c) digestion
  d) decoction
  e) percolation
  f) distillation
  g) expression

Page 18

• Solvents commonly used for extraction:
  a) petroleum ether – fats, fixed oils, waxes, pigments, resins
  b) ether/chloroform – alkaloids, resins, glycosides
  c) 95% EtOH – glycosides, tannins, saponins, resins
  d) 80% EtOH – same as 95% EtOH (phytochemical screening preferred)
  e) water – glycosides, sugar, salt, gums, proteins
  f) 1% HCl – alkaloids, salts of vegetable acids
  g) 5% NaOH – pentosans and hemicelluloses

Page 19

• Plant Metabolites:
  1) Primary metabolites – abundant but often lower value; examples: CHON, CHO, lipids
  2) Secondary metabolites – unique to species; often therapeutic; examples: alkaloids, steroids, flavonoids

Page 20

• Derivatives/extractives – compounds separated from crude drugs by extraction; chief constituents of the drug; product of extraction

• Menstruum – solvent used in extraction with selective action

• Marc – undissolved portion remaining after extraction

Page 21

• Geographic source and habitat:

  • Indigenous plants: grow in native countries

  • Naturalized plants: grown in foreign land outside their country of origin

Page 22

• Preparation of drugs for the commercial market:
  1) Collection – optimal when active principles are highest; material dries well for quality and appearance
  2) Harvesting – methods: hand labor or mechanical devices (hand labor often essential for skilled selection)

Page 23

• Collection rules by plant part:
  1) Leaves – mature
  2) Flowers – as they begin to open
  3) Underground parts – after vegetative growth ceases
  4) Bark – before vegetative growth begins
  5) Gums and resins – during dry weather
  6) Leaves and tops – not dew or rain-covered; reject if insect-damaged
  7) Fruits – mature but not ripe
  8) Seeds – mature but before the fruit opens

Page 24

• Drying methods and purposes:

  • Sun drying, artificial heat (40–60°C), or shade drying

  • Purposes: remove moisture for shelf life; facilitate comminution; inhibit enzymes, molding, bacterial action; prevent chemical changes; fix constituents; convert for handling

Page 25

• Drying principles:
  a) temperature control
  b) air flow regulation

• Curing: modified drying converting inert constituents to active form (example: vanilla)

Page 26

• Garbling: final step to remove extraneous matter

• Packaging, storage, and preservation:

  • Packaging depends on final disposition of the drug; protect from moisture, light, air, insects, high temperature; economy of space

Page 27

• Storage concerns: Moisture

  • Excess moisture increases weight and reduces active constituents; promotes enzymatic activity and fungal growth

• Light: adversely affects highly colored drugs; can cause undesirable changes in constituents, especially photosensitive drugs

Page 28

• Air/Oxygen: promotes oxidation of constituents

• High Temperature: detrimental to thermolabile substances and volatile constituents

Page 29

• Insects affecting drugs belong mainly to orders Lepidoptera, Coleoptera, Diptera

• Insect-control methods:
  1) expose to 65°C (most efficient)
  2) fumigation with methyl bromide
  3) store in tight, light-resistant containers; add few drops of CHCl3/CCl4

Page 30

• ANIMAL DRUGS:

  • From wild sources (e.g., whale, musk deer)

  • From domesticated animals (sheep, hog, honeybee, cattle)

  • Slaughterhouses are common sources of glandular products and enzymes

  • Processing and purification vary by drug

Page 31

• Evaluation of Drugs:

  • Purpose: determine quality and purity or identify drugs

• Quality: intrinsic value; amount of medicinal/active principles/constituents present

Page 32

• Methods of evaluating drugs:
  1) Organoleptic – macroscopic appearance, odor, taste, sound of fracture, feel
  2) Microscopic – essential for identification and adulterants in powders
  3) Pharmacologic/Biologic assay (bioassay) – using living animals or organs; indicates strength; may include microorganisms

Page 33

• Methods continued: 4) Chemical assay – standard method for potency; examples: colorimetric tests 5) Physical tests – rarely used for crude drugs but common for active principles (alkaloids, volatile oils): solubility, specific gravity, optical rotation, refractive index, melting point, moisture 6) Instrumental – e.g.,

  • UV-VIS spectroscopy (plant pigments)

  • IR spectroscopy (fingerprinting, functional groups)

  • Mass spectroscopy (molecular weight)

  • NMR spectroscopy (structural formula)

Page 34

• Instrumental methods overview (as above): UV-VIS, IR, Mass, NMR

Page 35

• Classification of Vegetal Drugs (study headings):
  1) Alphabetical – Latin or vernacular names
  2) Morphological – grouped by plant/animal part
  3) Taxonomic – based on botanical classification or phylogeny
  4) Pharmacologic/Therapeutic – based on therapeutic use or action of active constituent
  5) Chemical/Biogenetic – based on therapeutically/chemically active constituents

Page 36

• Two main groups of plant constituents:
  1) Active constituents – responsible for therapeutic effect (examples: glycosides, alkaloids, terpenes)
  2) Inert constituents – no definite pharmacologic activity (examples: cellulose, lignin, suberin, cutin, starch, albumin; in animals: keratin, chitin, muscle fiber, connective tissue)

Page 37

• Two classes of active constituents:
  1) Pharmaceutically active – cause precipitation/chemical changes in preparations (example: tannin)
  2) Pharmacologically active – responsible for therapeutic activity (examples: glycosides, alkaloids)

Page 38

• Constituents may be:
  1) A single chemical substance – examples: sugars, starches, plant acids, enzymes, glycosides, steroids, alkaloids, proteins, hormones, vitamins
  2) Mixture of principles – examples: fixed oils, fats, waxes, volatile oils, resins, oleoresins, oleo-gum-resins, balsams

Page 39

• Principal factors influencing secondary constituents:
  1) Heredity (genetics) – influences qualitative/quantitative changes; phenotypes resemble genotypes
  2) Ontogeny (development stage) – constituents vary with plant development
  3) Environmental factors – soil, climate, flora, cultivation methods

Page 40

• Drug biosynthesis/biogenesis:

  • Study of biochemical pathways leading to formation of secondary constituents used as drugs

  • Aim: understand pathways and interrelationships

Page 41

• Plant/Family name changes (new vs old names):

  • Examples:
    1) Brassicaceae (Old: Cruciferae) – Mustard
    2) Poaceae (Old: Graminae) – Grasses
    3) Lamiaceae (Old: Labiatae) – Mint
    4) Arecaceae (Old: Palmae) – Palm
    5) Umbelliferae – Apiaceae – Parsley
    6) Fabaceae (Old: Leguminosae) – Beans
    7) Asteraceae (Old: Compositae) – Sunflower
    8) Clusiaceae (Old: Guttiferae) – Mangosteen

Page 42

• Module 2: BDRP Cardohydrates (Carbohydrates)

• Institution: University of San Agustin

Page 43

• Carbohydrates definition:

  • Group of compounds C, H, O with H and O in same proportion as in water, formula often expressed as (CH2O)n , hydrates of carbon

• Etymology and initial definition: arose from belief that carbohydrates were hydrates of carbon

• Limitations of the definition include: (see details on Page 44)

Page 44

• Drawbacks of the simple hydrates definition:
  1) Not all organic compounds with H and O in water-like proportion are carbohydrates (e.g., ext{formaldehyde } H2CO ext{ as } C(H2O); acetic acid CH3COOH as C3(H2O)2; lactic acid CH3CH(OH)COOH as C3(H2O)3)
  2) Many carbohydrates do not have the usual H:O ratio (e.g., rhamnose C6H{12}O5, cymarose C7H{14}O4, digitoxose C6H{12}O_4)
  3) Some carbohydrates contain N or S in addition to C, H, O

Page 45

• Modern chemical definition:

  • Carbohydrates are polyhydroxy aldehydes or polyhydroxy ketones, or compounds that hydrolyze to yield such units

• Roles in plants: first products of photosynthesis; contribute to plant biomass

• Functions:

  • Cellulose provides rigid framework

  • Starch serves as food reserve

  • Sugars form glycosides and secondary metabolites

Page 46

• Molecular weight and properties:

  • Low molecular weight carbohydrates: crystalline, water-soluble, sweet (e.g., ext{glucose}, ext{fructose}, ext{sucrose})

  • High molecular weight carbohydrates (polysaccharides): amorphous, tasteless, less soluble (e.g., ext{starch}, ext{cellulose}, ext{inulin})

Page 47

• Carbohydrates classification:

  • Monosaccharides

  • Disaccharides

  • Trisaccharides

  • Tetrasaccharides

  • (Biosynthetic terms: and their abbreviations in the notes)

Page 48

• Bioses (biosynthetic small units):

  • Trioses contain two carbon atoms; not free in nature; example glyceraldehyde

• Four carbon sugars: Tetroses (e.g., erythrose, threose)

Page 49

• More details on tetrases (structure snippets shown in diagrams in the source)

Page 50

• Pentoses: common in plants; products of hydrolysis of polysaccharides like hemicelluloses, mucilage, gums (examples: ribose, arabinose, xylose)

Page 51

• Hexoses: monosaccharides with six carbon atoms; abundant in plants; subdivided into aldoses and ketoses

  • Aldoses: ext{Glucose}, ext{mannose}, ext{galactose}

  • Ketoses: ext{Fructose}, ext{sorbose}

Page 52

• Visual representations of glucose, mannose, galactose, fructose (D- and L- forms shown in the figures)

Page 53

• Disaccharides:

  • Hydrolysis yields two monosaccharides

  • Examples:

  • Sucrose → Glucose + Fructose

  • Maltose → Glucose + Glucose

  • Lactose → Glucose + Galactose

Page 54

• Trisaccharides:

  • Hydrolysis yields three monosaccharides

  • Examples:

  • Raffinose → Glucose + Fructose + Galactose

  • Gentianose → Glucose + Glucose + Fructose

• Tetrasaccharides:

  • Example: Stachyose → four monosaccharides

Page 55

• Summary table for disaccharides, trisaccharides, and tetrasaccharides (names, hydrolysis products, occurrences)

• Notable examples include: sucrose, maltose, lactose, raffinose, gentianose, stachyose, mogens (as listed in the source)

Page 56

• Polysaccharides:

  • Hydrolysis yields an indefinite number of monosaccharides

  • Condensation of monosaccharides forms polysaccharides

  • Types of hydrolysis products include pentosans and hexosans

  • Examples: xylan (pentosan); starch, insulin, cellulose (hexosans)

Page 57

• Cellulose vs starch structure:

  • Cellulose: glucose units linked by eta-1,4 linkages

  • Starch: glucose units linked by ext{α-}1,4 and ext{α-}1,6 linkages

• Polyuronides, gums, and mucilages exist as other important polysaccharide derivatives

Page 58

• Photosynthesis overview:

  • Carbohydrates arise from photosynthesis, converting light energy to chemical energy

  • Overall: 2 ext{H}2 ext{O} + ext{CO}2 + ext{light}
    ightarrow ( ext{CH}2 ext{O}) + ext{H}2 ext{O} + ext{O}_2

Page 59

• Metabolic flow schematic (conceptual):

  • Photosynthesis pathway feeds into glucose, which in turn enters various metabolic pools and pathways leading to monosaccharides, disaccharides, polysaccharides, and glycosides

Page 60

• Carbohydrate-containing drugs: examples include ext{Sucrose}, ext{Dextrose}, ext{Fructose}, ext{Lactose (various dairy products)}, ext{Lactulose}, ext{Xylose}, ext{Cherry Juice}

Page 61

• Metabolically related sugar compounds:

  • Glycolytic and oxidative metabolism products (plant acids such as citric, lactic, tartaric acids; alcohols such as beer, wine, brandy, whiskey, rum)

  • Reductive metabolism products (sugar alcohols like mannitol, sorbitol)

Page 62

• Polysaccharides and polysaccharide-containing drugs:

  • Starch (amylose and amylopectin)

  • Inulin

  • Dextran

  • Cellulose derivatives (e.g., methylcellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, cellulose acetate phthalate, sodium CMC)

Page 63

• Gums and mucilage:

  • Natural plant hydrocolloids; classified as anionic/nonionic polysaccharides or salts of polysaccharide

  • Produced by higher plants as protective after injury; upon hydrolysis yield arabinose, galactose, glucose, mannose, xylose, uronic acids; form salts with Ca, Mg, etc.

  • Gums: dissolve in water; mucilages: physiologic products that form slimy masses in water

Page 64

• Sources of commercially useful gums:

  • Shrub/tree exudates (Acacia, Karaya, Tragacanth)

  • Marine gums (Agar, Algin, Carrageenan, Furcellaran)

  • Seed gums (Cydonium, Guar, Locust bean, Psyllium)

  • Microbial gums (Dextran, Xanthan)

  • Plant extracts – Pectin (soluble pectin, protopectin, pectic acid)

Page 65

• Sources of pectin:

  • Plant sources: Pomelo, Orange, Dalanghita, Ponkan, Kalamansi, Lemon, Lime

  • Scientific names provided for each source (e.g., Citrus grandis, Citrus aurantium, Citrus nobilis, Citrus sinensis, etc.)

Page 66

• Module 3: BDRP Glycosides

• Focus: Glycosides (structure, classification, biosynthesis)

Page 67

• Definition of a glycoside:

  • A molecule where a sugar group is bonded through its anomeric carbon to another group via a glycosidic bond

  • Glycosidic bond forms between hemiacetal of a saccharide and hydroxyl of an alcohol

  • Glycone (sugar portion) and aglycone/genin (non-sugar portion) can be separated by hydrolysis in acid

• Enzymes: enzymes can form/break glycosidic bonds

Page 68

• Glycone and aglycone:

  • Glycone: sugar portion; may be a single sugar or multiple sugars

  • Aglycone: non-sugar portion; preferentially soluble in organic solvents

• Glycosides in plants: synthesized and hydrolyzed via specific enzymes; typically soluble in water/alcohols; aglycone soluble in benzene/ether

Page 69

• Sugar stereochemistry and general properties:

  • Sugars in glycosides are typically β-type; natural glycosides commonly contain β-sugars

  • Glycosides are a broad category with many sugar-aglycone combinations

• Classification basis: glycone, glycosidic linkage type, aglycone

Page 70

• Basis for glycoside classification:

  • By glycone

  • By glycosidic linkage

  • By aglycone

Page 71

• Basis of glycone classification:

  • If glycone is glucose → glucoside

  • If glycone is fructose → fructoside

  • If glycone is glucuronic acid → glucuronide

Page 72

• Basis of glycosidic linkage:

  • 1) O-glycosides: sugar bonded to phenol or –OH of aglycone (e.g., amygdaline, indicine, arbutin, salicin, cardiac glycosides, anthraquinone glycosides like sennosides)

  • 2) N-glycosides: sugar bonded to N of –NH in aglycone (nucleosides)

Page 73

• O-Glycosides representation and examples:

  • General schematic and a notable example: Rhein-8-glucoside from rhubarb

Page 74

• N-Glycosides:

  • Representation and examples: Adenosine (found in yeast nucleic acids)

Page 75

• S-Glycosides and C-Glycosides:

  • S-Glycosides: sugar attached to sulfur/thiol group of aglycone (e.g., Sinigrin from black mustard)

  • C-Glycosides: sugar directly attached to carbon of aglycone (e.g., Aloin, Cascarosides)

Page 76

• S-Glycosides detail:

  • S-Glycosides structures and example: Sinigrin (from Brassica juncea) with THIOglycoside linkage

Page 77

• C-Glycosides detail:

  • Examples: Aloin (Barbaloin) in Aloe; Cascarosides (A, B, C, D) with diverse stereochemistry

Page 78

• Glycoside classes overview:

  • Anthraquinone glycosides (e.g., senna, aloe, rhubarb)

  • Sterol or cardiac glycosides (Digitalis, Thevetia, Squill, etc.)

  • Saponin glycosides

  • Cyanogenetic and cyanophoric glycosides

  • Thiocynate/isothiocyanate glycosides

  • Flavone glycosides

  • Aldehyde glycosides

  • Coumarin and furanocoumarin glycosides

  • Phenol glycosides

  • Steroidal glycosides (overview)

  • Bitter and miscellaneous glycosides

Page 79

• Biosynthesis of glycosides (general):

  • Glycosides are condensation products of sugar and an aglycone (acceptor)

  • Step 1: sugar phosphates + UTP → UDP-sugar (sugar-uridine diphosphate)

  • Step 2: UDP-sugar + acceptor (glycosyl transferase) → glycoside + UDP

  • Subsequent enzymes may add more sugar units to form di-, tri-, or tetraglycosides

Page 80

• Anthracene glycosides:

  • Found mainly in dicot plants; aglycones include anthraquinones, anthraquinones related derivatives (anthrones/anthranols)

Page 81

• Anthracene glycosides characteristics:

  • Anthrones insoluble in alkali; anthranols soluble in alkali show strong fluorescence

  • Reduced anthraquinones are more active; fresh drugs contain reduced aglycones; storage leads to oxidation/hydrolysis

Page 82

• Anthracene structure and properties:

  • Anthraquinone: C${14}$H${8}$O$_{2}$; yellow/grey crystalline powder; melts at 286°C; boils at 379.8°C; insoluble in water/alcohol; soluble in nitrobenzene and aniline; chemically stable under normal conditions

Page 83

• Images and relationships among anthracene-related compounds: anthraquinone, anthrone, oxanthrone, anthranol, dianthranol (structural overview)

Page 84

• Sterol or Cardiac glycosides:

  • Important natural drugs with heart effects; used in treatment of congestive heart failure and atrial fibrillation/flutter

Page 85

• Cardiac glycoside aglycone features:

  • Steroid nucleus with fused ring system; 3-OH linked to sugar attachment; 14-OH present

  • Lactone moiety at C-17 is crucial

Page 86

• Lactone types and natural classes:

  • Cardeno-lides (unsaturated butyrolactone) vs bufadienolides (pyrone ring)

Page 87

• Lactone specifics:

  • Cardenolides lactone: single double bond; C23 steroids

  • Bufadienolides lactone: two double bonds; C24 steroids

Page 88

• (Figure references) Cardenolide and Bufadienolide diagrams

Page 89

• Saponin glycosides:

  • Saponins described as natural detergents; foaming in water; hemolytic activity; sneezing effect; toxicity; form complexes with cholesterol; antibiotic properties

  • Active role in plant immune systems

Page 90

• Saponin properties:

  • Often not crystalline; amorphous powders with high molecular weight

  • Contain many stereocenters; optically active

  • Usually water-soluble; soluble in ethanol/methanol; generally insoluble in nonpolar solvents

  • Bitter taste; cause sneezing; lower surface tension

Page 91

• Steroidal saponins and sapogenins:

  • Interact with cardiac glycosides, sex hormones, vitamin D, etc.

  • Diosgenin is a key steroid sapogenin

  • Families with steroidal saponins include Solanaceae, Apocynaceae, Liliaceae, Leguminosae

Page 92

• Triterpenoid saponins (sapogenins):

  • Lather in water; used as detergents or emulsifiers; exhibit antifungal, antimicrobial, and adaptogenic properties

  • Common in families: Rubiaceae, Compositae, Rutaceae, Umbelliferae

Page 93

• Tetracyclic and pentacyclic triterpenoids diagrams (structure references)

Page 94

• Cyanogenic glycosides:

  • Hydrolysis yields hydrocyanic acid (HCN), benzaldehyde, and sugars

  • Activity linked to hydrocyanic acid; characteristic of Rosaceae; examples: Amygdalin (bitter almond), Prunasin (wild cherry bark)

Page 95

• Isothiocyanate glycosides (glucosinolates):

  • Sulfur-containing glycosides common in Cruciferae; hydrolysis yields isothiocyanate (-NCS)

  • Examples: Sinigrin (black mustard), Sinalbin (white mustard), Gluconapin (rapeseed)

Page 96

• Flavone glycosides:

  • Contain phenylbenzopyrone system; occur free or as glycosides (O- or C-glycosides) with derivatives like flavone, flavonol, flavanone, isoflavone, chalcones

  • Examples: Rutin, quercitrin, hyperoside, diosmin, hesperidin, vitexin

Page 97

• Coumarin and furanocoumarin glycosides:

  • Aglycone is coumarin; benzopyrone derivatives with characteristic fluorescence under alkaline conditions

  • Biosynthesis via hydroxylation, glycolysis, and cyclization of cinnamic acid

  • Clinical value as precursors for anticoagulants (e.g., warfarin)

  • Furanocoumarins are toxic; found in Rutaceae, Umbelliferae, Leguminosae

Page 98

• Continued coumarin/furanocoumarin notes:

  • Coumarins have flavoring properties; potential liver toxicity

  • Furanocoumarins: linear and angular types

Page 99

• Aldehyde glycosides:

  • Vanilla pod contains glucovanillin; cinnamon bark contains cinnamic aldehyde

Page 100

• Phenol glycosides:

  • Aglycone often features phenolic/moieties; vegetative products like willow bark (containing salicin) and bearberry leaves (bearing arbutin) used historically for antipyretic and urinary antiseptic effects

Page 101

• Table 21.1: Phenolic glycosides examples, sources, and hydrolysis products (selected entries)

  • Examples include Salicin (Salix spp.), Arbutin (Populus spp. and Rosaceae), Phloridzin, etc.

  • Hydrolysis products listed (e.g., salicyl alcohol, glucose; vanillin, glucose; gallic acid + glucose, etc.)

Page 102

• Bitter and miscellaneous glycosides:

  • Bitter glycosides play a digestive role; used as stomachics, febrifuges, bitters; stimulate digestive juice secretion

Page 103

• Biosynthesis of Anthracene Glycosides (4.3.1):

  • Emodin and related derivatives biosynthesis studied via Penicillium islandicum

  • Proposed intermediate poly-β-ketomethylene acid from 8 acetate units; intramolecular condensation yields anthraquinones (e.g., emodin)

  • Alternative pathway (Alizarin) via shikimic acid–mevalonic acid mediators; Rubiaceae example

Page 104

• Biosynthesis of Phenol Glycosides (4.3.2): Arbutin biosynthesis via shikimic acid route involving phenylalanine and hydroquinone to Arbutin; pathway includes cinnamic acid

Page 105

• Biosynthesis of Steroid Glycosides (4.3.3):

  • Biotransformation of steroids and cardiac glycosides in plant cell cultures documented

  • General steroid biogenesis pathway: Acetate → Mevalonate → Isopentenyl pyrophosphate → Steroid backbone (head-to-tail assembly)

Page 106

• Biosynthesis of Flavonoid Glycosides (4.3.4):

  • Enzymatic steps postulated; more than 20 flavonoid glycosides detected in irradiated parsley cells

  • Aglycones mostly share similar substitution; two main biosynthetic pathways:

  • Acetate pathway

  • Shikimic acid pathway

  • One 6-carbon fragment from acetate combines with a 9-carbon fragment from shikimate/phenylpropanoid pathway

Page 107

• Biosynthesis of Coumarin and Furanocoumarin Glycosides (4.3.5):

  • Grafting experiments show roots essential for coumarin; fruits accumulate furanocoumarins; no evidence for translocation

  • Two demonstrated pathways for bezopyran nucleus-containing compounds:

  • Pathway A: polyketide-derived for some coumarins; phenylpropanoid shikimate linkage

  • Pathway B: shikimate-chorismate pathway leading to phenylpyruvic acid; phenylalanine via transamination → cinnamic acid

  • Linear vs angular furanocoumarins shown

Page 108

• Biosynthesis of Cyanogenetic Glycosides (4.3.6):

  • Cyanogenesis: hydroxynitrile glycosides hydrolyzed by cellular enzymes to hydroxynitriles (HCN) when tissue is disrupted

  • Key cyanogenic glycosides and families: dhurrin (Sorghum spp.), prunasin (various families; listed genera)

  • Tyrosine and phenylalanine concept: shikimic acid pathway contributes to these amino acids; phenylalanine pathway produces prunasin from phenylalanine

Page 109

• Biosynthesis of Thioglycosides (4.3.7):

  • Mustard-family glycosides yield isothiocyanate glycosides; aglycones may be aliphatic or aromatic

  • Acetate is incorporated into allyl moiety of Sinigrin (Brassica juncea) via a labeled acetate experiment

Page 110

• Biosynthesis of Saponin Glycosides (4.3.8):

  • Two main types: steroidal saponins (spiroketal side chain) and triterpenoid saponins

  • Acetate/mevalonate labeling shows incorporation into spiroketal steroids and pentacyclic triterpenoids; branching likely after squalene formation

  • Pathways converge on squalene, then diverge to spiroketal steroids or pentacyclic triterpenoids

Page 111

• Biosynthesis of Aldehyde Glycosides (4.3.9):

  • Aromatic nuclei of aldehyde glycosides originate from C6-C3 precursors via Shikimic Pathway

  • The conversion of cinnamic acid to vanillin is proposed via shikimate and phenylalanine routes

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• Module 3: Tannins (BDRPH)

• Tannins overview: complex, non-nitrogenous plant products with astringent properties; widely distributed in plants; term coined by Seguin (1796)

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• Tannin classification (Goldbeater’s skin test):

  • True tannins – positive tanning test

  • Pseudotannins – partially retain on hide powder and do not give full tanning test

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• True tannins vs pseudotannins: high molecular weight tannins are often true tannins; condensed tannins also called proanthocyanidins

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• True tannins characteristics:

  • Usually high molecular weight and complex polyphenolics; may form glycosides

  • Hydrolyze with mineral acids/enzymes

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• Hydrolysable tannins:

  • Hydrolyzed by mineral acids or enzymes (tannase)

  • Consist of polyphenolic acids (gallic, hexahydrodiphenic, ellagic) esterified to glucose

  • Gallotannins vs ellagitannins (ellagic acid after intraesterification)

  • Soluble in water; blue color with ferric chloride

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• Hydrolysis products: gallic acid, ellagic acid

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• Nonhydrolysable (condensed) tannins:

  • Not readily hydrolyzed; sometimes called proanthocyanidins

  • Related to flavonoids; organisms like catechin (flavan-3-ol) and leucoanthocyanidins (flavan-3,4-diol)

  • Often linked to carbohydrates or proteins; upon acid/enzymes, polymerize to phlobaphens (red color)

  • On dry distillation yield catechol derivatives; soluble in water; give green color with ferric chloride

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• Structural examples:

  • Catechin and Leucoanthocyanidin structures displayed

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• Pseudotannins:

  • Simple phenolics of lower molecular weight; do not respond to Goldbeater’s tanning test

  • Examples include gallic acid, chlorogenic acid, catechin

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• Characteristics of tannins (summary):

  • Colloidal in water; non-crystalline; soluble in water, alcohol, dilute alkali, glycerin; sparingly soluble in ethyl acetate; insoluble in many organic solvents; molecular weight from ~500 to >20,000; oligomeric with multiple phenolic units; can bind to proteins

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• Biosynthesis of tannins (phenolics pathway):

  • All phenolics are formed via the shikimic acid/phenylpropanoid pathway

  • Hydrolysable tannins: gallic/ellagic acids derived from gallic acid; ellagitannins formed via hexahydroxydiphenic acid esters to glucose

  • Proanthocyanidins: biosynthetic precursors are leucocyanidins; auto-oxidation forms anthocyanidins and related compounds; polymerize to PAs

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• Glycosides and tannins (selected examples):

  • List of glycosides associated with tannins and related plants (examples include Cascara sagrada, Frangula, Aloe, Rhubarb, Senna, Ginseng, Digitalis, Salicin, etc.)

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• Final note: Thank you