Alkaloids
The majority of the alkaloids are found in the plant
kingdom, from higher plants down to microorganisms.
Few are found in the animal kingdom, and curiously
enough, alkaloids are represented extremely sparsely in
the marine environment.
Alkaloids derived from Onithine and Lysine. The
pyrrolidine and piperidine alkaloids Ornithine is an
immediate precursor for the pyrrolidine alkaloids.
Pyrrolidine and piperidine
N
H N
H
pyrrolidine piperidine
Robinson synthesis of Tropinone
COOH
CH
CHO
+ NH2CH3 N+ CH3 + O CO2
CHO
CH
OH COOH
H3C
CH2 N
+
NCH3 O
CO2 .
COOH
Lupine alkaloids
4
7
2 6
9
N H N H N H
H H H
Pelletierine (+) Coniine Pinidine
Biosynthesis of Coniine
CH3COOH
HOOC HOOC
[H]
[NH2]
OHC [H]
N N
Coniceine Coniine
The biosynthetic path followed by the
Nicotiana alkaloids depicts that the
aromatic ring is not derived from lysine by
cyclization and dehydrogenation.
Its immediate precursor is nicotinic acid,
the important provitamin trivially called
niacin. Deficiency of nicotinic acid leads to
pellagra in humans and black tongue in
dogs. I was first prepared by the oxidation
of nicotine with nitric acid.
COOH
H N
CH3
N N
Nicotinic acid
Nicotine
Biosynthesis of nicotinic acid
OP
HO COOH
HO COOH COOH
1. [NH2]
+ 2. Cyclization
N HN
O H N
CH2 Nicotinic acid
CH2
PLP
PLP
Alkaloids from Tyrosine
The indole alkaloids which primarily are
confined to three plant families,
Apocynaeae, Loganiaceae, Rubiaceae,
attracted interest, partly because of their
significant neurophysiological action.
COOH COOH
NH2 O [O]
HO HO
HO COOH
O
HO
HO COOH HO
PLP
NH2 NH2
HO HO
Dopa Dopamine
HO HO
HO PL
COOH + NH N CH
NH2 HO HO
O HO COOH CO
Dopamine O H
HO HO
H2O
PLP
CH3O CH3O HO
NCH3 NH NH
HO HO HO
HO
H H [CH3] HO
H
HO
CH3O HO
CH3O
Norlaudaosoline
(S)-Reticuline Nor-reticuline
CH3O
N
CH3O
CH3O
H
CH3O
Papavaerine
Alkaloids derived from tryptophan. The indole alkaloids
Biosynthesis of some simple tryptophan alkaloids.
COOH HO NH2
1. [O]
NH2 2. -CO2
N N
H H
5-Hydroxytryptamine
1. -CO2
2. Pyruvate
3. -CO2
[CH3]
HO N(CH3)2
CH3
NH HO
N N
H CH3 H
N N
Elaeagnine Bufotenine
CH3 CH3
Elaeagnus Bufo vulgaris
augustifolia Eseroline
[O]
NHCH3
CH3
OCO
N N N
N
CH3 CH3 CH3
H
Physostigmine
Harmane Physostigma
Passiflora venenosum
incarnata
Alkaloids derived from
Anthranilic acid
The structural unit pertaining to anthranilic
acid is recognized in several alkaloids
having the quinoline, acridine and
quinazoline skeletons. They are frequently
represented in the Rutaceae family.
COOH COCoA N
N
NH2 NH2 Quinoline Acridine
Anthranilic acid Coenzyme A activated
anthranilic acid
OH O
N N
N
N N N
Phenazine OH
Peganine OH
O
Iodinin
Biosynthesis of a quinoline alkaloid in Pseudomonas aeruginos
CH3COOH + 4 CH2(COOH)2
Aceic acid Malonic acid
COCoA
COCoA
+
O NH2
OH
N
Plausible pathway for the biosynthesis of Peganine in
Peganum harmala
Ornithine
COCoA N N
+
NH2 N
OH
Peganine
[O] Peganum harmala
Terpenoids
Terpenoids form groups of compounds in
which majority occur in the plant kingdom.
The simple mono and sesquiterpenoids
are the chief constitutents of the essential
oils.
Most natural terpenoid hydrocarbons have
the molecular formula (C5H8)n, and the
value of n is used as the basis for
classification.
No of carbons Class
i) 10 Monoterpenoids (C10H16)
ii 15 Sesquiterpenoids (C15H24)
iii 20 Diterpenoids (C20H32)
iv 25 Sesterterpenoids (C25H40)
v 30 Triterpenoids (C30H48)
vi 40 Tetraterpenoids
(Carotenoids, C40H64)
vii >40 Poly terpenoids (C5H8)n
Isoprene Rule
Divisibilty ito isoprene units may be
regarded as necessary condition to be
satisfied by the structure of any plant
synthesized terpenoids. Units are joined in
Head-to-tail fashion.
C C
C C
C C
C C C C C C C C C C C C
C C C C C C
C C C
C C C C C C C C C C C C
C C C C
acyclic structure p-cymene structure
Bicyclic monoterpenoids contain six-
membered ring and a three, four or five
membered ring.
Isolation of Monoterpenoids and
Sesquiterpenoids. Essntial iols in plants.
Four methods of extraction 1. Expression
2. steam distillation
3. extraction by means of volatile solvent
4. adsorption on purified fat
Purification: TLC, Column Chromatography
and Gas chromatography has been
particularly useful for isolating pure
configurational forms of a given
terpenoids.
Monoterpenoids: Subdivided into three
groups- acyclic, monocyclic and bicyclic.
Myrcene (C10H16) b.p. 166-168oC
CH2
H3C
C CH CH2 CH2 C CH CH2
H3C 7 6 5 4 3 2 1
7-methyl-3-methyleneocta-1,6-diene
O
O3 O CO2H
+ 2CH2O + CHO CrO3
+ CO2
CHO CO2H
Ocimene : C10H16
b.p. 81o/30mm
Ocimene occurs in the leaves of Ocimum
basilicum. When catalytically dehydrogenated,
ocimene adds on three molecules of hydrogen
to form a decane.
Thus ocimene which contains three double
bonds. Since it forms an adduct with maleic
anhydride, then two of the double bonds are
conjugated. On ozonylysis, ocimene produces
formaldehyde, methyl glyoxal, laevualdehyde,
acetic and malonic acids and acetone.
2CH2O CHO
COOH
+ + CH2 + CH3COOH
COOH
CHO O
I
COOH
O + CH2O
+ CH2 +
CHO
COOH
II
Structural elucidation favours II
When heated Ocimene isomerizes
into III allo-ocimene in which three
double bonds are conjugated
III
Citral C10H16O
This is the most important member of the acyclic
monoterpenoids. It id widely distributed in lemon grass (60-
80%) and possesses a lemon smell.
C
C
C C
C
C C
C C
acyclic structure
CHO
O
1. KMnO4 CO2H + O
+
2. CrO3
CO2H CO2H
oxalic acid acetone laevulic acid
CHO
CHO
O +
CH3
Tiemann Synthesis (1898)
O
OH
Br CO2Et
+
Na CH(COEt)2 NaOH
Br
O 1. Zn/ICH2O2Et
AC2O
+
2. H H2O
O
CHO
(HCO2)2Ca
CO2Et Ca salt
Arens Synthesis 1949
Br
HO Zn-Cu HO
PBr2
O i Na-liq NH3
+ C2H2 H2O
ii H2O
OH OH
i) EtOC CMgBr H2
1.NaEAA O
2. OH 3. H+ ii) H+ Pd-BaSO4
CO2Et CO2Et
H+
CHO
Ionones
When citral is condensed with acetone in
the presence of barium hydroxide, ψ-
ionone is formed and this on heating with
dilute H2SO4 in the presence of glycerol
forms a mixture of α- and β–ionones.
O O O
CHO O +
Ba(OH)2 H+
+
+
O ionone
O
B ionone a ionone
O
CO2H
[O] CO2H
O + +
CO2H CO2H
Geronic acid 2,2-Dimethyl succinicc a
B ionone 2,2-Dimethyl adipic acid
O
O
CO2H
[O] + CO2H
+
CO2H CO2H
CO2H
isogeronic acid 3,3-Dimethyl adipic acid 2,2-Dimethyl glutamic acid
o
Geraniol C10H18O b.p. 229-230 C/757mm
CH2OH
o
Linalool C10H18O b.p. 198-199 C
OH
OH
+ +
+ CH2OH
+ i H
i H
ii H2O ii H2O
Geraniol
O Na OH
O
i NaNH2/Et2O H2O Na moist
ii C2H2 Et2O
OH
O
+ CH2=CHMgBr
+ Linalool
Lavandulol C10 H18 O b.p. 94-95o C/13 mm
HOH2C
Citronellal C10H18O
CrO3 O
CHO +
CO2H
CO2H
H2 Na/Hg
CHO CH2OH
Catalysis
Citronellal Citronellol
Diterpenoids Phytol
(C20H40O) b.p 145oC/0.03 mm. Parent Hydrocarbon is
C20H42 (CnH2n+2)
Diterpenoids
O3
C18H36=CHCH2OH C18H36O + OCHCH2OH
Saturated Ketone Glycoaldehyde
O
Phytol
Diterpenoids
Geranyllinalyl isonitrile R=N=C
Formamide R=NHCHO
isothiocyanate R=NCS
AcO
OAc
Trifarin
Aromatic diterpenes
Aromatic diterpenes
OH OH
13 OH HO
c c HOOC
14
H H H
Ferruginol Totarol Carnosic acid
Podocarpus ferruginea Podocarpus ferruginea Rosmarinus officianalis
CH2OH CH2OH i PBr3
H2-Pd
ii NaEAA
Farnesol Hexahydrofarnesol
O
KOH
O
+
CO2Et H
1. NaNH2
H2-Pd
2. CH=CH
+
3. H OH OH
AC2O
Phytol OH
Pheromones
In recent years important discoveries have been
made showing unexpected biological effects by
seemingly uninteresting compounds. Chemical
ecology gathers a number of chemically guided
behaviours in animals and plants.
Biologists realize long ago that scent induced
specific behaviours in animals, but it was until
1959, when the first sex attractant bombycol was
isolated in the female silk moth, Bombyx mori, and
that real interdisciplinary research started on
pheromones, the chemical compounds acting as
attractants.
The signal power of some sexual attractants is
enormous. The attractants released by a single
female silk moth under favourable wind conditions
can affect a male at a downwind distance of several
kilometres.
The male begin to react at concentrations as low
as 100 molecules per cm3. We can imagine what
great confusion these signals will create in a
community containing thousands of species if they
were not highly specific.
OH
Bombycol (Bombyx mori)
Pheromones……. contd
Scent from flowers of Ophrys orchids attracts
insects and induces coupulatory behaviour in
specialized bees. During these movements on
the labellum, pollination is accomplished. Some
of the compounds responsible for these
chemical signals are simple sesquiterpenes.
Female gametes of the brown algae Ectocarpus
siliculosus, Cutleria multifida and Fucus serratus
produce simple low molecular unsaturated
hydrocarbons that attract and effect the
locomotory behaviour of the male gametes.
Sex attractants isolated from insects
COOCH3
Methyl (E)-2,4,5-tetradecatrienoate (Acanthoscelides obtectus)
H
OH
O OH
O (E,E)-3,7-Dmethyl-2,6-decadien-1,10-diol
Danaus gilippus
exo-Brevicomin
Dendroctonus brevicomis
OH
cis-Verbenol
Ips typographus
Sex attractants from brown alga
H
Fucoserratene
Ectocarpene Multifidene
Trail pheromone from Atta texana
H3C
COOCH3
Mammalian pheromones
CH3CH=CHCH2SH CH3COCOCH2CH2SCH3
Mephitis mephitis Hyaena hyaena
HO H
Sus scrofa
Moschus moschiferus
