Download L19 Alkaloids MedicinalPlants

General Information about Vit A
*In plant kingdom we don't have Vit A but we have only Pro Vit A.
*The Vit A itself is only found in animal.
*Vit A is a fat soluble vitamin.
*Have recommended diagnoses by (6000 IU).
*It is involved in many different physiological functions such as vision
and reproduction.
*Vision defects result from deficiency of Vit A.
*Not only the Vit A deficiency lead to defects but also overdose of Vit A
can end up in pathological condition , when Vit A dose exceeds 10000
IU this produces teratogenic effects.
*Pro vit rarely causes pathological conditions.
*Major abnormal rxn of Vit A is observed by synthetic product of Vit A
which is used for acne.
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*Retinoic acid and its isomer ( 5-cis retinoic acid or iso retinoic acid
which are marketed as tretinoin and iso-tretinoin)can be involved in
the occurrence of malformation in the fetuses so pregnant women
should not take them (teratogenic)
* Retinoic acid and iso-retinoic acid are used for treatment of acne
vulgaris .
* Vit D is sun vitamin (can be obtained by exposure to sun)
*When we said Vit A we mean Vit A1.
*3,4-dihydroVit A1 (The source of Vit A2)
*New Vit A has cis double bond at the carbon 5.
 There is a subgroup of carotenoids which is Carotenoic
Acids and a very well known example is Crocetin.
*Crocetin is a dicarboxylic acid and it is obtained by saffron stigmas.
*Crocetin has one carboxylic acid at each end so it is found in plant in
the form of glycoside (Crocein).
*Crocein is made by forming ester linkage between crocetin and
disaccharide (gentiobiose sugare).
*In plant Crocus sativus we found crocetin and crocein and it contains
colored stigmas and also Crocus sativus is used as expensive spice .
*Stigmas in flowers are orange in color and are responsible for this
spice characteristic.
*And may be used as coloring agent depending on crocein .
*And use as aroma (‫ )تعطي نكهة‬which it is originating from aldehyde
Safranal.
*So crocien and crocetin responsible of yellow/orange coloring of
this spice and safranal responsible for flavoring.
*To obtain 1 kg of these stigmas you will need 100 thousand flower
heads of this plant so it is the most expensive spices.
*In the past, Saffron was not used because abortifiacient effect, but
recently based on guinea pig, they discovered no abortifacient effect
unless we have high dose.
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* Recently based on superoxide scavenger activity, Saffron is used for
preservation of sperms.
 There are 2 groups of secondary metabolites obtained by tail to
tail condensation which are tri and tetra terpenes. now we will
start with last chapter of terpenoid which is known as
polyterpenes and are product of head to tail condensation , by
using up to million IPP units can be attached by head to tail
and produce this huge molecular weight of terpenoids.
 And there are 2 different subgroups of polyterpenes either all
cis polyterpenes or all Trans polyterpenes, and the most
common in the nature are the all cis polyterpenes. And about
2000species of higher plants produce polyterpenes.(So it is
widely distributed in different plant species)
 Achras sapota most presentative use of polyterpenes.
 Achras sapota gives elasticity of chewing gum.
 These substances are not found in nature as they are, but we
make chemical modification on them to improve elasticity and
strength of the substance in nature.
 Polyterpenes have different uses.
* We talked about different pathways (AMP , MAP , SAP ) and now we
will to talk about nitrogenous compounds because there is no single
certain pathway of the previous chapters that talked about
nitrogenous compounds. And the alkaloid includes biggest group of
these nitrogen substances.
 Terpenes, glucosydolase and biogen deaminase these small
chapters contain nitrogen substances.
 1819 first discovered of alkaloids by pharmacist.
 Alkaloid is heterogenic compounds.
 Alkaloid is from plant origin and has basic characteristic and
contain nitrogen in heterocyclic ring.
 Alkaloid has biological, pharmacological, physiological, and
toxic activity.
 Definition of alkaloid by basicity, nitrogen in heterocyclic, plant
origin and biological activity , but there are deviation from this
definition , so we use new definition.
Alkaloids new definition: Alkaloids are cyclic organic
compounds containing nitrogen in a negative state of oxidation
with limited distribution among living organisms.
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There are many classification of alkaloids.
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Aromatic a . a
Aliphatic a .a
Origin from shikimic
acid pathway
 Pharmacological effects according to physiological action.
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True alkaloids (Typical , classical , real alkaloids) it has
different pharmacological and physiological reactions.
Proto-alkaloids: contain amine group from amino acids
(a.a).
N in the side chain.
Proto-alkaloids : it is known as Biogenic amine
a.a
decarboxylation
biogenic amine … then there are
several rxns (oxidation, methylation , ethylation and
cylization).
Pseudo – alkaloids: have nitrogen in heterocyclic
structure so we need to know what is the nitrogen donor.
Pseudo-alkaloids are produced by subsequent
transamination rxn , using nitrogen either from glutamate or
aspartate or ammonia.
Pseudo alkaloid produced from other precursor ( from
other a.a )
False – alkaloids : Not alkaloid ! .. No nitrogen in their
structure...Nothing to do…but gives false positive rxn with
alkaloidal reagents in classical identification rxn ... like
furanocoumarine, percabtane react with alkaloidal substances
but it is not alkaloid, may be called as new alkaloid.
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*Distribution and Occurrence of Alkaloid:
* Primarily, Alkaloids are produced by vascular plants (Higher
plants) which are divided into of mono- and di- cotyledons, but the
di-cotyledons are more rich in alkaloids than monocotyledons.
*Ergometrine: it is an alkaloid originating from fungi and it is
potent and is still used.
*Plant families containing alkaloids are not for memorizing 
*Alkaloids are distributed in any organ of plant like roots, leaves,
seeds, fruits…etc
*In Solanaceae family we cannot find final decision about the
part of plant which contains alkaloids . there are diff parts contain
alkaloids according to the species of plant.
Solanaceae
alkaloids ‫يعني كل اجزاء النبات فيها تحتوي‬
Solanaceae
(Nicotiana tobacco)
*(Tomato) lycopericon is free from alkaloids.
*(Potato) Folam tuberusea
when exposed tubers to sun it
will form sprout which is rich in solanine glycosidic alkaloids.
*Atropa belladonna contains alkaloids in seeds and leaves.
Solanaceae family
*You should know which forms of alkaloids are found in the
plant because this help in isolation of the alkaloids.
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(It is easily extracted by pure organic solvents like chloroform.)
[Salts can be extracted by 70%
alcoholic solvents(methanol ,ethanol)]
Addictive agent
Free bases with sugar
*alkaloids in the form of salts with acids, we can split the acids by
bases (such as nitrate,ammonia) so then we will take the alkaloids as
free bases .
*always alkaloids are found in combination with acids, sugars…then
we make a certain rxn to get alkaloids as free bases.
*Identification of meconic acid by FeCl3.
Few drops of FeCl3 + Opium powder( contain Meconic acid)
Intensive Red color
* There is also an ecological importance of alkaloids (about 5000
compounds).
*alkaloids are very toxic and bitter so the animals and insects avoid
plants which contain alkaloids.
*There are major and minor alkaloids.
(Suffixes and prefixes)
*Closely related alkaloids are determined by prefix and suffix (which
depend on organic chemistry)
By isolating alkaloids of similar structure, we should name them by
using useful prefixes and suffixes. I said some of these prefixes and
suffixes are similar to other synthetic compounds of the organic
chemistry,, for example :
Nor- designates demethylation or demethoxylated derivative of
original compound ex ;ephedrine, norephedrine.
Apo- prefix are the loss of molecule of water or dehydrated
derivatives; morphine, Apomorphine, atropine, Apoatropine .
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** iso, pseudo, neo and epi : always prefixes used for designating
isomeric compounds.
**The suffix (dine) refers to isomers as: quinidine and cinchonidine for
example: different isomers and different biological activity.
**(ine) : additionally added, refers specially by ergot alkaloids to
designate the inactive representative or limited derivative of this
isolated compound.
Physical properties of the alkaloid:
1. Condition: most of the alkaloids occurring in nature are solid and
crystalline; they can be easily obtained in the pure form from simple
recrystallization or changing the solvent that is needed for
crystallization.
There are some alkaloids that are solid but not crystalline
(amorphous), and their purification might take time more than the
crystalline.
But solid alkaloids are easier to obtain than liquid alkaloids, some
alkaloids are curing elements, most liquid alkaloids (in general not all
of them) are the non-oxygenated alkaloids by volatile oil.
If there is oxygen in there structure = solid
If it's non oxygenated = liquid and the liquid alkaloids may be volatile
oil or nonvolatile oil in the case of quinine or nicotine ( volatile liquid)
while in the case of pilocarpine and hyoscine ( nonvolatile liquid ).
2. Color: most of the alkaloids are white or whitish crystalline
substances but still we have different color of alkaloid like peramines,
autosein and panadien. .
3. Solubility: in fact the introduction we mentioned depends on the
form of occurrence of synthetic alkaloids; either in form of free bases
or in form of their salt and this type of occurrence is affecting the
solubility.
In general alkaloid bases and the salts have certain solubility in
alcohol but we never use alcohol for extraction, we prefer to convert
alkaloids either to their free bases type or salt in order to be selecting
one solvent for isolation.
The bases in general are soluble in organic solvents and among
organic solvent chloroform has a special position. Primarily it's used
for extraction of bases. Water can be used for the extraction because
the salts quaternary ammonium bases are water soluble substances
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and easily can be isolated in the water or the hydro-alcoholic solution
but again like many characteristic of the alkaloids we have exceptions;
there are a lot of bases like caffeine, we are using the coffee in water
boiling coffee in preparing it and get the ring of the caffeine so it's a
free base but it is soluble in water.
So depending on the solubility we say that alkaloids in the basic form
are soluble in organic solvents, and those in the salt form are soluble
in water. Some pure bases are not soluble in organic solvents (or in a
specific organic solvent), because alkaloids’ solubility was not only
tested in chloroform but in other solvents as well. Alkaloids have been
tested by series of organic solvents.
They are carried by magically active compounds, you will find endless
list of free bases insoluble alkaloids on it for example; they are
insoluble in ether for example.
And similarly, not all salts are soluble in water; there are water
insoluble salts like quinine.
Isomerization: is common observation in alkaloid chemistry so when
we write hyosciamine, we have to classify it in D or L or racimate. So,
optical rotation is important because there are differences in their
biological activity due to their isomerization.
In general L- form have more or stronger biological activity compared
to D- form, exception d-Tubocurarine is more active.
Also there should be signs like letters or (+),(-) always accompanied
with the name of alkaloids example : quinine and quindine are optical
isomers but they exhibit different biological activity. It’s obligatory to
write optical rotation whether they are D or L; because according to
their rotation they are either anti-malarial activity(L-quinine) or anti
arrhythmic activity(quinidine : d-form) .
Chemical properties :
1. Nitrogen: Alkaloid has 1 to 5 nitrogen atoms and that indicates
whether it’s primary, secondary, tertiary amines or quaternary
ammonium base.
2. Basicity : ( basicity depends on # of nitrogen n-substituted
functional grp.. primary is the most basic )
**Saturated hexacyclic amines > basic than aromatic amines, and
according to this we can classify them to weak, strong, amphoteric.
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Generally alkaloids are basic but sometimes they are neutral like
quaternary non basic secondary metabolite like: colchicine.
3. Oxygen: in general most alkaloids with oxygen are solid and non oxygen alkaloids are liquid.
4. Stability: In the form of salt alkaloids are more stable compared to
free bases.
A. The effect of heat and light: not specific to alkaloids many
secondary metabolites are affected by them. There are important
criteria when we are making melting point: alkaloids decompose
forming blackish mass rather than melting.
** Important procedure is roasting green beans of coffee to get caffeine
when roasted in covered containers then extracted we get a thick layer
of crystalline caffeine.
B. reactions with acids: alkaloids occur in the basic form and when we
add diluted acids they will convert to their salt forms. Acids they can
hydrolyze esters for examples.
Concentrated acids can cause: dehydration, demethoxylation.
C. alkaline media: we can use them for extraction; can liberate
alkaloids from their salts. They can form salts with alkaloids having
COOH grp, strong alkaline media can hydrolyze esters including
opening the lactone ring (because they are inner ester ring), they split
the ester bond regardless aliphatic or cyclic.
D. effect of light: Like many other secondary metabolites, alkaloids
should be kept or stored without exposure to heat and light and
oxygen of the air therefore quite unexpected degradation or
degradation compound can occur if not kept in amber glass container.
For example, color of alkaloid is changing because of the effect of the
light to convert them to inactive metabolite.
Some of inactive metabolites is Eserine and Reserpine when exposed
to light they degrade giving rubreserine, decomposition. We can
recognize eserine and or phystostigmine are white crystalline
substance while its degradation product is dark red color so
immediately recognize that there is negative effect of light and air
oxygen especially when there is alkaline media available.
By other alkaloids there is deterioration without changing in color; so
you need some experiment in order to detect degradation product.
Others can be decomposed to dark masses, sticky masses, ex; ergot
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alkaloid epimerization to inactive Lumi alkaloids.
QUALITATIVE TEST FOR ALKALOIDS:
primarily there are general alkaloid test and specific alkaloid test;
-general test : can be applied to all classes of alkaloids.
-specific test: for certain pure compound, or certain class or related
compounds, for example; marqui test for caffeine, while taloquine for
quinine.
We cannot obtain positive result by change other alkaloid.
The majority of alkaloid tests are general tests, which either will
change color or form precipitate (ppt), so we have general coloring
agent or precipitating agent.
We use these tests to detect the presence of alkaloids and –after
extraction- to know whether the extraction was complete or not.
Unfortunately there are some secondary metabolites that respond in
similar manner to alkaloid reagents.
Pseudo alkaloids, false alkaloids are non-alkaloid substances such as
coumarines and flavonoids that give positive result to the reagent,
direct you to wrong way so you lose some material and time and cost.
Therefore, they do not depend on one single test, they make 5,6,7
different tests :color test and ppt test in order to ensure that alkaloids
occur in the plant material , because not all reactions give +ve test.
Identification of alkaloids
* Melting point for any pure compound, repeat several time.
* D- L- isomers must be determined for alkaloids.
* HPLC  more time saving.
*GC-MS for volatile, so for alkaloid nonvolatile mixed with TMS
(TriMethylSilyl) to be determined by GC-MS.
Examples of alkaloids
*Chemical skeleton you must know basic nuclei
*Phenylalkylamine= aromatic ring +alkyl chain +( N) amide.
*Tropanesolanaceae
*Atropine: 6-membered ring.
*Steroidal  typical tetracycilc
*Terpenoid: mono- & diterpenoid.
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