1. Natural Product
The organic compounds isolated from the living organism i.e plants, animals and micro organism are generally known
as Natural products. These includes carbohydrates, protein,
aminoacids, alkaloides, terpenes, antibiotics etc
The term natural product is applied to material derived from plants microorganisms and invertebrates, which are fine biochemical’s factories for synthesis of both primary and secondary metabolites OR

4. Bacteria and Fungi as source for Biologically active Compounds

5. Classical and Advance methods

9. Structure of Morphine

10. ‘Tinkering’ with the structure of morphine produced heroin

11. The heart beat may be too fast or too slow

25. Terpenoids

26. INTRODUCTION
Terpenoids are the secondary metabolites synthesized by plants, marine organisms and fungi by head to tail joining of isoprene units. They are also found to occur in rocks, fossils and animal kingdom.
Isoprene

27. Isoprene (2-methyl-1,3-butadiene)
Terpenes
Terpenes are natural products that are structurally related to isoprene.
H2C C
CH3 CH
CH2 or
Isoprene (2-methyl-1,3-butadiene)

28. Introduction to Natural Products
Isoprene

29. Introduction to Natural Products
Head
Isoprene
Tail
Head
Tail

30. Introduction to Natural Products
Head
Isoprene
Tail
Head
Tail

31. Classification of Terpenes
Terpenes and terpenoids posses a carbon fram work consisting of five carbon units known as isoprene unit.
It is represented by symbol C5H8
In oldest days the term terpene was used for those compounds containing 10 carbon atoms.
This is still used in Modern classification of Terpenes.
Terpenes are classified in to the following groups.
Hemeterpens 1 x C5H8 = C5H8
Monoterpens x C5H8 = C10H16
sesquiterpens 3 x C5H8 = C15H24
Diterpens x C5H8 = C20H32
sesterpens x C5H8 = C25H40
triterpens 6 x C5H8 = C30H48
Tetraterpenes 7 x C5H8 = C35H58
Polyterpenes n x C5H8 = C5H8)n
Rubber n= 100 or above
Classification of Terpenes

32. CALASSFICATION hemiterpene C5 one monoterpenoid C10 two
TYPE OF NUMBER OF ISOPRENE
TERPENOIDS CARBON ATOMS UNITS
hemiterpene C5
one
monoterpenoid
C10
two
sesquiterpenoid
C15
three
diterpenoid
C20
four
sesterterpenoid
C25
five
triterpenoid
C30
six
tetraterpenoid
C40
eight
NOTE:
hemi = half di = two
sesqui = one and a half tri = three
tetra = four

33. Mnonoterpenoids
Monoterpenes are a class of terpenes that consist of two isoprene units and have the molecular formula C10H16.
Monoterpenes may be linear (acyclic) or contain rings. Biochemical modifications such as oxidation or rearrange-ment produce the related monoterpenoids.

34. a-Phellandrene (eucalyptus)
Representative Monoterpenes OH O H
a-Phellandrene (eucalyptus)
Menthol (peppermint)
Citral (lemon grass)

35. a-Phellandrene (eucalyptus)
Representative Monoterpenes OH O H
a-Phellandrene (eucalyptus)
Menthol (peppermint)
Citral (lemon grass)

36. a-Phellandrene (eucalyptus)
Representative Monoterpenes
a-Phellandrene (eucalyptus)
Menthol (peppermint)
Citral (lemon grass)

37. Mnonoterpenoids Acyclic monoterpenoid: Bicyclic monoterpenoid
Monocyclic monoterpenodi

38. Acyclic monoterpenoid
Biosynthetically, isopentenyl pyrophosphate and dimethylallyl pyrophosphate are combined to form geranyl pyrophosphate
Geranyl pyrophosphate

39. Acyclic monoterpenoid
Elimination of the pyrophosphate group leads to the formation of acyclic monoterpenes such as ocimene and the myrcenes.
Myrcene

40. Acyclic monoterpenoid
Hydrolysis of the phosphate groups leads to the prototypical acyclic monoterpenoid geraniol.
geraniol

41. Acyclic monoterpenoid
Additional rearrangements and oxidations provide compounds such as citral, citronellol, and many others.
citral

42. Acyclic monoterpenoid
Many monoterpenes found in marine organisms are halogenated, such as halomon.
Halomon is a polyhalogenated monoterpene first isolated from the marine red algae Portieria hornemannii.
It has attracted research interest because of its promising profile of selective cytotoxicity that suggests its potential use as an antitumor agent.
Halomon

43. Monocyclic monoterpenoid
In addition to linear attachments, the isoprene units can make connections to form rings. The most common ring 　size 　in monoterpenes is a six-membered ring.
A classic example is the 　cyclization　 of　 geranyl pyrophosphate to form limonene.

44. Bicyclic monoterpenoid
Geranyl pyrophosphate can also undergo two sequential cyclization reactions to form bicyclic monoterpenes, such as pinene which is the primary constituent of pine resin.

45. Bicyclic monoterpenoid
Other bicyclic monoterpenes include carene and camphene.
Camphor, borneol and eucalyptol are examples of bicyclic monoterpenoids containing ketone, alcohol, and ether functional groups, respectively.
carene
camphor borneol

46. Sesquiterpenoids
Sesquiterpenes are a class of terpenes that consist of three isoprene units and have the molecular formula C15H24.
Like monoterpenes, sesquiterpenes may be acyclic or contain rings, including many unique combinations.
Biochemical modifications such as oxidation or rearrangement produce the related sesquiterpenoids.

47. Representative SesquiterpenesH
a-Selinene (celery)

48. Representative SesquiterpenesH
a-Selinene (celery)

49. Representative Sesquiterpenes
a-Selinene (celery)

50. Sesquiterpenoids Monocyclic sesquiterpenoids Acyclic sesquiterpenoids
Bicyclic sesquiterpenoids

51. 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 . Oxidation can then provide sesquiterpenoids such as farnesol.
Sesquiterpenes are found naturally in plants as defensive agents.
farnesene
farnesyl pyrophosphate
farnesol

52. Monocyclic Sesquiterpenoids
With the increased chain length and additional double bond, the number of possible ways that cyclization can occur is also increased, and there exists a wide variety of cyclic sesquiterpenes. In addition to common six-membered ring systems such as is found in zingiberene, a consitituent of the oil from ginger, cyclization of one end of the chain to the other end can lead to macrocyclic, rings such as humulene.
zingiberene

53. Bicyclic Sesquiterpenoids
In addition to common six-membered rings such as in the cadinenes, one classic bicyclic sesquiterpene is caryophyllene, from the oil of cloves which has a nine-membered ring and cyclobutane ring. Additional unsaturation provides aromatic bicyclic sesquiter- penoids such as guaiazulene.
caryophyllene

54. Tricyclic Sesquiterpenoids
With the addition of a third ring, the possible structures become increasingly varied. Examples include longifolene, copaene and the alcohol patchoulol.
isomers of patchoulol
longifolene
copaene

55. Diterpenoids

56. Diterpenoids
Diterpenes are composed for four isoprene units and have the molecular formula C20H32. They derive from geranylgeranyl pyrophosphate.
Examples of diterpenes are cafestol, kahweol, cembrene and taxadiene (precursor of taxol).
geranylgeranyl pyrophosphate
cafestol
cembrene

57. Representative DiterpenesOH
Vitamin A

58. Representative DiterpenesOH
Vitamin A

59. Representative Diterpenes
Vitamin A

60. Diterpenoids
Diterpenes also form the basis for biologically important compounds such as retinol, retinal, and phytol. They are known to be antimicrobial and antiinflammatory. The herb Sideritis contains diterpenes.
retinal
retinol

61. Structure ----Diterpenoids
Monocyclic diterpenoids
Acyclic diterpenoids
Bicyclic diterpenoids
Tricyclic diterpenoids
Tetracyclic diterpenoids

62. Triterpenoids

63. Triterpenoids
Triterpenes consist of six isoprene units and have the molecular formula C30H48. The linear triterpene squalene, the major constituent of shark liver oil, is derived from t he reductive coupling of two molecules of farnesyl pyrophosphate. Squalene is then processed biosynthetically to generate either lanosterol or cycloartenol, the structural precursors to all the steroids.
squalene
farnesyl pyrophosphate
lanosterol
cycloartenol

64. Squalene (shark liver oil)
Representative Triterpene
tail-to-tail linkage of isoprene units
Squalene (shark liver oil)

65. Structure ----Triterpenids
Acyclic triterpenids　　squalene
Bicyclic triterpenids
α-carotene
β-carotene

66. Structure ----Triterpenids
Tetracyclic triterpenids
Dammarane Lanostane Tirucallane
Cycloartane Cucurbitane

67. Structure ----Triterpenids
Pentacyclic triterpenoids
Oleanane Ursane Lupane

68. Citral C10H16O
It is the most important member of the most of the acyclic monoterpenoides. Because the structure of most of the other compounds in this group are based on that of citral. Its is widely distributed and occurs to an extent of % in lemon grass oil. It is a liquid which has the smell of lemons.

69. Structure of Citral. The molecular formula of citral is C10H16O
analogue of saturated hydrocarbons
CnH2n+2
C10H10x2+2 = C10H22
IHD: /2 = 3
From IHD it is found that the citral contains 3 double bonds

70. Cat. Hydrogentation
On cat. Hydrogenation 2 moles of hydrgone were consumed. This showed that the molecule contain 2 C=C bonds

71. Bromination
On bromination also two molecule of bromine were consumed. This also proved that molecule contain 2 C=C bonds.

72. Nature of Oxygen ( formation of oximes)
Citral was converted into an oxime on treatment with NH2-OH. This reaction showed that molecule contains an oxo group.

73. Reduction
Citral is reduced to an alcohol geraniol ( C10H18O) . Geraniol is a primary alcohol and the formation a primary alcohol form carbonyl compound confirmed that the citral contains an aldehyde functional group.

74. Oxidation
Oxidation of citral with Ag2O gives geranic acid C10H16O2 and no loss of carbon atom takes place. This further proves that oxo group in citral is an aldehyde group.

75. Reaction with potassium hydrogen sulphate
On heating with KHSO4 citral form P-Cymene. This reaction was used by semmler to determine the position of methyl and isopropyl group in the skeleton structure 1
This reaction showed that the citral molecule is acyclic in which two isoprene Units are joined in head to tail manner

76. Stereochemistry
The examination of the formula of citral shows that 2 geometrical isomers are possible
The functional group may be Cis or Trans.
These structure are supported by NMR spectroscopy

77. Synthesis
Synthesis of citral can be carried out by the following synthetic route.

78. Catalytic Hydrogenation
Bromination

79. Formation of oxime

80. Reduction
Citral is reduced to an alcohol geraniol ( C10H18O) . Geraniol is a primary alcohol and the formation a primary alcohol form carbonyl compound confirmed that the citral contains an aldehyde functional group.

81. Essential Oils

82. Essential Oils Terpenes and terpenoids are the primary constituents
of the essential oils of many types of plants and flowers.
Essential oils are used widely as natural flavor additives
for food, as fragrances in perfumery, in aroma therapy,
and in traditional and alternative medicines. Synthetic
variations and derivatives of natural terpenes and ter-
penoids also greatly expand the variety of aromas used
in perfumery and flavors used in food additives.

83. ISOLATION & SEPARATION TECHNIQUES
Essential oils containing mono- and sesquiterpenoids are obtaind
by water and or steam distillation of the part such as flowers, lea-
-ves of stems, where the essential oils occur in more concentrated
form. Due to the heat lability of certain constituents of essential oils
different distillation methods have to be used for different raw m-
-erials which are briefly described below:

84. Distillation
Today, most common essential oils, such as lavender, peppermint, and eucalyptus, are distilled. Raw plant material, consisting of the flowers, leaves, wood, bark, roots, seeds, or peel, is put into an alembic (distillation apparatus) over water. As the water is heated the steam passes through the plant material, vaporizing the volatile compounds. The vapors flow through a coil where they condense back to liquid, which is then collected in the receiving vessel.

85. Distillation
Most oils are distilled in a single process. One exception is Ylang- ylang (Cananga odorata), which takes 22 hours to complete through a fractional distillation.

86. Distillation
The recondensed water is referred to as a hydrosol, herbal distillate or plant water essence, which may be sold as another fragrant product. Popular hydrosols are rose water, lavender water, lemon balm, and orange blossom water. The use of herbal distillates in cosmetics is increasing. Some plant hydrosols have unpleasant smells and are therefore not sold.

87. Expression
Most citrus peel oils are expressed mechanically, or cold-pressed. Due to the large quantities of oil in citrus peel and the relatively low cost to grow and harvest the raw materials, citrus-fruit oils are cheaper than most other essential oils. Lemon or sweet orange oils that are obtained as by-products of the citrus industry are even cheaper.
Prior to the discovery of distillation, all essential oils were extracted by pressing.

88. Solvent extraction
Most flowers contain too little volatile oil to undergo expression and their chemical components are too delicate and easily denatured变by the high heat used in steam distillation. Instead, a solvent such as hexane or supercritical carbon dioxide is used to extract the oils. Extracts from hexane and other hydrophobic solvent are called concretes, which is a mixture of essential oil, waxes, resins, and other lipophilic (oil soluble) plant material.

89. Solvent extraction
Although highly fragrant, concretes contain large quantities of non-fragrant waxes and resins. As such another solvent, often ethyl alcohol, which only dissolves the fragrant low-molecular weight compounds, is used to extract the fragrant oil from the concrete The alcohol is removed by a second distillation, leaving behind the absolute.

90. ISOLATION & SEPARATION TECHNIQUES
Terpenoids
Following methods are employed for the extraction of mono-, sesqui-, di-, tri-, and tetraterpenoids.
Air dried powdered part of the plant is extracted by percolation or soxhlet
extraction successively with organic solvents with increasing polarity such as
petroleum ether, benzene, diethyl ether, chloroform, ethyl acetate, acetone,
ethanol, methanol and water. The extraction efficiency can be increased with
the decrease in the time of the process by stirring the pulverized plant material
using mechanical stirrer with the chosen solvent and filtering it to obtain the
extract.

91. STRUCTURE ELUCIDATION
Physical Mehtods
Molecular formula
Specific rotation
Refractive index
Spectral Methods for Structure Determination UV IR MS
NMR

92. Physical Mehtods Molecular formula 2. Specific rotation
Determination of the molecular formula of an isolated pure terpenoid is done by finding
out the empirical formula and molecular weight. Empirical formula can be found out by elemental
analsis .While molecular weight can be determined by vapour density, elevation of boiling
point and depression of freezing point.
Specific rotation
Specific rotation of a compound is measured to ascertain the optical activity exhibited by it. It helps
to distinguish between optical isomers.
Refractive index
It is measured to calculate the value of molecular refraction, which is useful to find out the nature
of the carbon skeleton especially in the case of sesquiterpenoids .

93. Spectral Methods
1. UV
Functional groups, present in terpenoids , which absorb in the UV range
between nm are termed as chromophores.However UV data becomes
valuable only when the terpenoid molecule contains conjugated double bonds
and/or α,β-unsaturated carbonyl group.
2. IR
This method is routinely used for the identification as well as the structure
elucidation of new terpenoids.
3. MS
FAB-MS affords the e xact molecular ion peak along with diagnostic
fragmentation patterns of the terpenoid molecule. It is an important tool for
the structure determination .

94. Spectral Methods
4. NMR
NMR spectroscopy comprising of both PMR and CMR is in fact one of the
Most important tools furnishing a good teal of information required for the
structure elucidation.
The combination of 1D selective and 2D NMR techniques such as COSY,
TOCSY, ROESY,2D IN-ADEQUATE, HMQC, HMBC COLOC, HOHAHA,
HETCOR and selective INEPT are of great value for the structure elucidation
of various terpenoids including the saponins and glyosides of a number
of sugar moieties.

95. EXAMPLE C10H16O b.p.77℃ UV:236nm IR:1665，1625，1603，1398，1190，1117cm-1.
MS:m/z 69(100),41,84,94,109,67,83,81
1H-NMR:1.65(6H，d， C-7 methyls) ，2.15(3H，s，C-3 Me)，5.0(1H，t， H-6)， 5.8(1H，d，H-2)， 9.84(1H，d，H-1).
13C-NMR:190(C-1)，127.5(C-2)，162.1(C-3)，40.5(C-4)，26.5(C-5)，123.5(C-6)，132.3(C-7)，25.3(C-8)，17.4(C-9)，17.0(C-10).

96. Thank you!