Terpenoids & Volatile Oils

Transcription

1 Terpenoids & Volatile Oils Mohammed N. Sabir

2 Introduction Uses in Plants & Medicine Classes of terpenoids Chemistry & Biosynthetic origin Monoterpenoids 2

3 Terpenoids Widely distributed natural products, mainly found in higher plants. Biosynthesized from mevalonic acid via acetate β- Plolyketide Pathway. 3

4 In Plants, they composed from dimerization and polymerization of single isoprene (isoprenoid) units. About 20,000 compounds related to terpenoids discovered CH 3 CH 3 H 3 C CH 3 H 3 C Head-to-tail conjugation CH 3 4

5 Biosynthetic origin of terpenoids Mevalonic acid Dimethylallyl PP (DMAPP) C 5 OPP Isopentenyl PP (IPP) C 5 OPP Hemiterpens C 5 C 10 Monoterpenes (C 10 ) IPP C 15 Sesquiterpenes (C 15 ) IPP C 20 Diterpenes (C 20 ) IPP C 25 Sesterterpenes (C 25 ) C 30 Triterpenes (C 30 ) Steroids (C 18 -C 30 ) 5 C 40 Tetraterpenes (C40 ) Carotenoids

6 Volatile Oils Are terpenoids (almost mono), they are oily substances and volatile at room temperature. 6

7 Role in Climate Monoterpenes are emitted by forests and form that can serve as Cloud Condensation Nuclei (CCN). Such aerosols can increase the brightness of clouds and cool the climate. 7

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9 Functions of terpenoids in Plants Insect repellants Insect attractant (Pollinating agents) Defensive agents Plant hormones Signaling molecules 9

10 Medicinal Uses of terpenoids As flavoring agents Antiflactulents Spasmolytic Expectorants Insect repellent Analgesic anti-inflammatory agents Cough suppressants Local anesthetics 10

11 Terpenes Hemiterpenes Monoterpenes Sesquiterpenes Diterpenes Acyclic Monocyclic Bicyclic Triterpenes OH Tetraterpenes 11 HO

12 Classification of terpenoids Hemiterpenoids (one isoprene unit) Monoterpenoids (two isoprene units) Acyclic Monocyclic Bicyclic Tricyclic Sesquiterpenoids (three isoprene units) 12

13 Classification of terpenoids Diterpenoids (four isoprene units) Triterpenoids (six isoprene units) Tetraterpenoids & carotenoids (eight isoprene units) Meroterpenoids 13

14 CALASSFICATION TYPE OF NUMBER OF ISOPRENE TERPENOIDS CARBON ATOMS UNITS hemiterpenes monoterpenes sesquiterpenes diterpenes triterpenes tetraterpenes C 5 C 10 C 15 C 20 C 30 C 40 one two three four sesterterpenes C 25 five six eight NOTE: hemi = half sesqui = one and a half di = two tri = three tetra = four 14

15 Bicyclic sesquiterpenoids 15

16 ing in carbon numbers, the possibilities of cyclization also ed. Therefore; a wide variety of cyclic terpenoids exists. 16

17 In addition to common six-membered ring systems such as zingiberene, a constituent of the oil from Ginger, cyclization of one end of the chains to the other end can lead to macrocyclic rings such as humulene. 17

18 Sesquiterpenes are a class of terpenes that consist of three isoprene units and have the molecular formula C 15 H 24. Sesquiterpenes may be acyclic or contain rings, including many unique combinations. 18

19 Biochemical modifications such as oxidation or rearrangement produce the related sesquiterpenoids. 19

20 OH Geraniol OH Farnesol Squalene Phytoene Methanol Bisabolene Taxadiene 20

21 Nomenclature of terpenoids -Oid suffix rather than ens -ene suffix should be restricted for the unsaturated hydrocarbon of the class -Isoprene units are linked head-to-tail manner -The number of isoprene units incorporated indicate the class of the terpenoid 21

22 Named either to IUPAC (systematic) or the trivial names Sometimes not only an isoprene oligomer, but rather saturated or partially saturated isomers as well as oxygenated derivatives such as alcohols, aldehydes, ketones, phenols, ethers and esters are involved in the structure. 22

23 Monoterpenoids -About 1,000 naturally occurring monoterpenoids have been isolated from higher plants. -Monoterpenoids are also found in secretions of insects. 23

24 Monoterpenoids -A characteristic feature of monoterpenoids are their volatility and intensely pungent odor -They are the most compounds responsible for plant fragrance (essential oils) 24

25 Classes of monoterpenoids A-Acyclic Monoterpenoids (Myrcane sub-class) Is the major component of Rose oil and occur in small quantities in lemon essential oils 25

26 Classes of monoterpenoids B-Cyclic Monoterpenoids 1-Monocyclic monoterpenoids (ex. p. Menthane) Found in:- -Eucalyptus oil Used in topical preparations for the treatment of muscle spasm (analgesic activity and in insect repellants (Citridiol )). 26

27 Classes of monoterpenoids 2-Bicyclic monoterpenoids Subclasses:- -Bornane -Carnane -Fenchone -Pinane -Thujane 27

28 CH 3 CH 3 CH 3 OPP H 2C OPP H PPO OPP H 3C CH 3 DMAPP H 3C CH 3 GeranylPP H 3C CH 3 Linalyl PP (Mycrane class) Menthane H Carnane Bornane Pinane 28 Thujane Fenchone

29 -Most of these monoterpenoids occur in nature as optically pure compounds. However some of which may present in some plants as both enantiomers. Ex:- (+) & (-) α-pinene in Pinus spp. 29

30 Turpentine oil (+) alpha-pinen (-) alpha pinen 30

31 -Camphor Is a ketone obtained from Cinnamomum camphora (Fam: Lauraceae) Also Rosemarinus officinalis Camphor = kafur Bicyclic bornane class CH 3 O CH 3 H 3 C Camphor 31

32 Medicinal uses -Local anesthetic -Anti-inflammatory -Antimicrobial -Antipruretic in conc % -Counterirritant for neuralgia & fibrositis. 32

33 -Common colds, externally applied for the chest in cough conditions, especially in Children -Inhalations of the aromatic vapors causes a local anesthetic action Vicks, Vaporub Extract obtained by steam distillation Synthetically, made from pinene 33

34 Cineol (eucalyptol) CH 3 Found in Eucalyptus globus and in Cajuput, Fam: Myrtaceae Also called cajuputol O Obtained from eucalyptus leaf oil and other sources by steam distillation. H 3 C Cineole CH 3 34

35 Medicinal Uses Flavoring agent Nasal inhalers for nasal congestion Antiseptic sprays Mild anesthetic for nose and throat Expectorant Analgesic 35

36 Menthol (menth-3-ol) Peppermint or Mint Is an alcohol obtained from divers mint oils and prepared synthetically. It is Levorotatory (-)-menthol when natural. The synthetic are racemic mixtures [( + )-menthol] 36

37 It is prepared form Japanese peppermint oil by freezing to (-220 o C), during which the menthol crystallizes. The liquid portion is poured off and the crystallized menthol is passed between filter papers and subsequently purified by recrystallization. 37

38 Also obtained by steam distillation of the flowering tops of Mentha arvensis, M. piperita Fam: Lamiaceae Synthetic racemic menthol is produced by hydrogenation of thymol CH 3 CH 3 +H OH OH H 3 C CH 3 H 3 C CH 3 38 Thymol Menthol

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40 Menthol occurs as colorless, hexagonal crystals that are usually needle like, as fused masses, or as a crystalline powder. 40

41 Medicinal uses:- In concentrations ranging from %, found in preparations used to treat minor burns and sunburns, poison ivy rash, athletics' foot. 41

42 In concentrations ( %) act as a counter irritant. Combined with Camphor and Eucalyptus oil (Cineol) in ointments, cough drugs, nasal sprays and inhalations to relieve symptoms of bronchitis, sinusitis and nasal congestion. 42

43 Small oral doses act as carminative, however larger doses have a depressant action on the heart. 43

44 Thymol Is a phenol obtained from thyme oil (Thymus vulgaris) [Lamiaceae] It may be prepared synthetically from m-cresol or p-cymene. CH 3 OH H 3 C CH 3 m-cresol CH 3 p-cymene 44

45 Thymol is an antifungal and antibacterial agent. It is more powerful than Phenol, but it s use is limited by its low solubility in water and because of it s irritation to skin. 45

46 It s included in topical antiseptic and analgesic preparations in concentrations ranging from % and oral gargles. 46

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48 Volatile Oils Are odorous principles found in various plant parts Since they are volatilize upon exposure to air, they are termed as volatile Some times also called essential oils related to essence, and also called ethereal oils 48

49 Spices are dried, fragrant, aromatic, or pungent plant parts that contain volatile oils are primarily used in food as seasoning rather than nutrition Depending on the plant family, volatile oils may occur in specialized secretary structures 49

50 Family Lamiaceae Pipraceae Apiaceae Pinaceae Occurrence Glandular hair Modified paranchymal cells Oil-tubes (Vittae) Schizogenous passages 50

51 They may be formed directly by the protoplasm through decomposition of the cell wall, or by hydrolysis of certain glycosides Plant Part Plant Conifer Rose Cinnamon All tissues Petals Bark and Leaves Mints Orange Glandular hair of stem and leaves Flower petals 51

52 The chemical constituents of volatile oils and spices are divided into two broad classes, based on their biosynthetic origin:- 1. Terpenoid (acetate, mevalonic acid) 2. Aromatic compounds (Shikimate) 52

53 Common physical properties of volatile oils 1. Characteristic odor 2. High refractive index 3. Optical activity 4. Special optical rotation 5. Immiscible with water 6. Soluble in ether, alcohol and organic solvents 53

54 Differences between volatile oils and fixed oils Volatile oils Can be distillated from the natural sources Don t become rancid Fixed oils Leave a permanent grease spot on paper Become rancid On exposure to light they oxidize and resinify Sapponified with alkalis Volatile at room temperature Not volatile 54

55 Volatile oils consist of chemical mixtures The presence of traces of the essential oils is essential for the aroma 55

56 Cinnamon Cinnamomum zeylanicum Plant part: Barks Fam: Lauraceae 56

57 Clove (Eugina) euginol Eugina caryophyllus E. caryophylata Syzygium aromaticum Plant part: Flowers Fam: Myrtaceae 57

58 Sesquiterpenoids Consists of three isoprene units and having the formula C 15 H 24. Like monoterpenes, it may be acyclic or contain rings, including many unique combinations. 58

59 Biochemical modifications such as oxidation or rearrangement produce the related sesquiterpenoids. 59

60 Sesquiterpenoids Acyclic sesquiterpenoids Monocyclic sesquiterpenoids O Á-farnesene Â-farnesene 姜稀 姜黄酮 Bicyclic sesquiterpenoids H OH H 60 Á-eudesmol cadinene guaiazulene

61 Acyclic Sesquiterpenoids When geranyl pyrophosphate reacts with isopentenyl pyro- phosphate, the result is the 15-carbon farnesyl pyrophosphate, which is an intermediate in the biosynthesis of sesquiterpenes such as farnesene 61

62 farnesene farnesyl pyrophosphate farnesol 62

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64 Oxidation can then provide sesquiterpenoids such as farnesol. Sesquiterpenes are found naturally in plants as defensive agents. 64

65 Monocyclic Sesquiterpenoids Increasing chain length and additional double bonds, the number of possible ways that cyclization can occur is also increased, there are a wide variety of cyclic sesquiterpenes. zingiberene 姜稀 65

66 In addition to common six-membered ring systems such as is found in zingiberene, a constituent of the oil from ginger, cyclization of one end of the chain to the other end can lead to macrocyclic rings such as humulene. 66

67 Sesquiterpene lactones The α-methylene-δ-lactone ring is essential for the pharmacologic actions. 67

68 Example of Sesquiterpenoids - Artemisinin Isolated from the plant Artemisia annua. Not all plants of this species contain artemisinin. Used to treat multi-drug resistant strains of falciparum. 68

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70 Its anti-malarial application was first described in Zhouhou Beji Fang "The Handbook of Prescriptions for Emergencies", edited in the middle of fourth century by Ge Hong. 70

71 In 1972, discovered artemisinin in the leaves of Artemisia annua 71

72 It was found that it cleared malaria parasites from their bodies faster than any other drug in history. 72

73 Cancer treatment is under early research and testing lactone peroxide group which comes into contact with high iron concentrations (common in cancerous cells), the molecule becomes unstable and releases reactive oxygen species. It has been shown to reduce angiogenesis and the expression of vascular endothelial growth factor in some tissue cultures. 73

74 Chamomile Dried flowering tops of Matricaria recutita (Astraceae) Bisabolol 74

75 Major constituents Bisabolol Bisaboloxides Matricin 75

76 H 3 C H 3 C HO CH 3 H 3 C H 3 C α-(-)-bisabolol a natural monocyclic sesquiterpene alcohol a colorless viscous oil almost insoluble in water well soluble in ethanol 76

77 Has weak sweet floral aroma and used in various fragrances. Be used for hundreds of years in cosmetics because of its perceived skin healing properties. - spasmolytic - anti-inflammatory - anti-microbial 77

78 Feverfew Dried leaves of Tanacetum parthenium (Astraceae) Contains Parthenolide CH 3 CH 2 78 H 3 C O O O

79 The drug has anti-migraine activity 79

80 Zingiberene is a monocyclic sesquitepenoid which is the predominant constituent of the oil of ginger (Zingiber officinale), from which it gets its name. 姜稀 80

81 The name 5-(1,5-dim--ethyl-4-hexenyl)-2-methyl-1,3- cyclohexadiene, chemical formulac 15 H

82 Diterpenes Diterpenes are composed for four isoprene units and have the molecular formula C 20 H 32. They derive from geranylgeranyl pyrophosphate. 82

83 Examples of diterpenes are cafestol, kahweol, cembrene and taxadiene (precursor of taxol) geranylgeranyl pyrophosphate 83

84 The first diterpenoids introduced were:- Abietic acid Gibberllins Podolactones Diesters of Phorbal Stevioside 84

85 Taxol (Paclitaxel) Overview a mitotic inhibitor used in cancer chemotherapy 1967, Wall and Wani Pacific yew tree, Taxus brevifolia Bristol-Myers Squibb (BMS) taxol ---- paclitaxel ---- trademark 'Taxol 85

86 Forskolin (Colforsin) Dried roots of the Indian herb Coleus forskohlii (Lamiaceae) 86

87 Contains Forskolin CH 3 CH 2 OH O CH 3 CH 3 O OH O O CH 3 H 3 C CH 3 OH 87

88 Ginkgolides Ginkgo is a genus of highly unusual non-flowering plants with one extant species, G. biloba, which is regarded as a living fossil. 88

89 Ginkgolides are biologically active terpenic lactones present in Ginkgo biloba. They are bicyclic diterpenoids, and there are six lactone-rings in their skeletons. 89

90 Ginkgolide B is an extract from the cultivated leaves of the Ginkgo Tree. Clinical studies have shown ginkgo to benefit short term memory, cardiovascular health, respiratory health and gastrointestinal health. 90

91 Ginkgolide B is an active platelet aggregating factor (PAF) antagonist. All ginkgo formulas must have adequate levels of ginkgolide B in order to successfully increase cerebral blood flow. 91

92 Triterpenes Triterpenes consist of six isoprene units and have the molecular formula C 30 H 48. The linear triterpene squalene, the major constituent of shark liver oil, is derived from the reductive coupling of two molecules of farnesyl pyrophosphate. 92

93 Squalene is then processed biosynthetically to generate either lanosterol or cycloartenol, the structural precursors to all the steroids. farnesyl pyrophosphate 93

94 Ginsenosides are a class of triterpene saponins, found exclusively in the plant genus Panax (ginseng). Ginsenosides have been the target of research, as they are viewed as the active compounds behind the claims of ginseng's efficacy. 94

95 Ginsenoside Rb 1 most abundant in Panax quinquefolius (American Ginseng). affect the reproductive system in animal testicles. recent research ---- affects rat embryo development. may increase testosterone production in male rats indirectly through the stimulation of the luteinizing hormone. inhibits chemoinvasion and angiogenesis. 95

96 Ginsenoside Rc is recognized for producing more sedative related results than other ginsenosides 96

97 In one particular study on breast cancer and different ginsenosides, it was found that only ginsenoside-rc was capable of inhibiting the growth of these cancer cells. This suggests that there is a possibility that ginsenoside-rc may have effects that prevent or limit the development of breast cancer. 97

98 A further study was also able to demonstrate a possible effect of ginsenoside-rc on the motility of sperm. Data from this experimentation showed a significant increase in motility when the sperm was in a ginsenoside-rc solution. 98

99 Ginsenoside Rg1 Most abundant in Panax ginseng (Chinese/Korean Ginseng). Improves the capability of spatial learning for mice, plus estrogen-like activity (which could account for the boosting of "yin" theory) 99

100 Tetraterpenes and carotenoids Vitamin-A Physiologic importance Deficiency 100

101 Some biologically important compounds such as retinol, retinal, and phytol. They are known to be antimicrobial and antiinflammatory. 101

102 H 3 C CH 3 CH 3 CH 3 H 3 C CH 3 CH 3 CH 3 Β-carotene 102

103 Preparations - Tretinoin - Isotretinoin 103

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105 Thank you 105