Download Sheet #27 (archive) Medicinal Plants

Medicinal plants – Sheet #27
2/5/2012

Pyridine and piperidine alkaloids
Alkaloids which are possessing either a pyridine or piperidine in their structure
are called pyridine-piperidine alkaloid,s allthough the origin of the pyridine and
piperdine can be of different amino acids. The first type we’ll talk about is
Coniine:
Coniine is an exceptional case where no amino acids are involved in providing
the N but the transamination rxn; the nature has no limits as you can see, as
we are used on the N not to be a part of a heterocyclic ring structure! , but
coniine is an exceptional case, its N is a result of transamination rxn and it’s
included in a heterocyclic ring.
You can always be surprised with the nature providing us with different toxic
and biologically active substances.
Coniine is the toxic principle of Conium maculatum plant which belong to the
Apiaceae family , its fruit is similar to anise fruits the same size and
appearance .
It exist in jordan in wadi shoaib , you can see the Conium maculatum next to
the anise plants they grow in the same climate conditions but the Conium is
the toxic plant in the family Apiacea .
As mentioned before ( hahahah 3a asas fe 7ad b7dar wela 3aref :p) a nonoxygenated substances are oily as in the case of Coniine .it’s an oily liquid as it
doesn’t have an oxygen in its structure ,it cause paralysis of the diaphragm (
interrupt respiration then death)
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Again the N should be originated from an amino acid but this is an exceptional
case it comes from transamination and here the acetic pathway is involved in
the biosynthesis
We have 4 acetate units ---- polyketomethylene ----- transamination --
cyclisation.
Sheet no. 24 :

Arecoline and Areca catechu
Arecoline
Arecaidine
Arecoline it’s from the family Arecaceae it’s called betel nut, the seeds contain
the active principle , it can occur as a single compound or with other closely
related alkaloids like its derivative Arecaidine .
It’s use is only important from the pharmacological point in the veterinary
medicine (‫ ) الطب البيطري‬it is used widly as a vermifuge ( ‫)مضاد للديدان‬
The precursor in its synthesis is the nicotinc acid which is formed by the rxn of
L-aspartic acid + 3-phosphoglycerylaldehyde and several intermediate
compounds are formed until nicotinc acid is formed then it is converted to
arecoline .
L-aspartic acid+ 3-phosphoglycerylaldehyde--- --- --- nicotinic acid-- - arecoline
In fact arecoline seeds are of importance for the veterinary medicine in south
Asia where the plant is growing in countries like India and Serilanka, but also
in these countries they chew the betel “betel chewing”, but they have to make
preparation of it to form chewing gum of it
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Leaves of the betel+lime (as the alkaline media) + tannin + betel nut (which
contain Arecoline) -- they chew it through the day to achieve a refreshment
and relaxation but hallucinations do not occur .
This relaxation effect result from the ( ARECAIDINE ) msh ARECOLINE rakzo
lw sam7to ;)
Demethylation of arecoline results in Arecaidine formation and that happens in
alkaline media (that’s why the lime used for) by the addition of lime when the
person chew the betel gum, arecaidine is formed and the accumulation of it is
responsible for the relaxation effect .
Adverse effect : can cause inflammation ,yellow teeth caused by the tannin ,
and over years with continuous use it can cause cancer!
The betel leaves and tannine-- for aroma.
The betel nut- responsible for the relaxation effect due to the arecaidine
formed from the arecoline.

Nicotine and Nicotina tabacum
When we talk about the pyridine-piperidine derivatives, the most important
representative is the Nicotina tabacum ( people smoke it), it is the oldest one of
the eldest attitudes of human being and the most officially acceptable social
behavior ( smoking cigarette)
Nicotina tabacum is the representative of the family Solanaceae ,so far around
100 species have been identified ,some of them are wild others are widely
culturated to cover the need of the cigarette industry
We have many alkaloids in this plant ,some of them are liquid but the most
important alkaloids found in Nicotina tabacum are:
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The diffrences between them that both the nicotine and nornicotine are based
on pyridine-pyrrolidine whereas the anabasine is based on the pyridinepiperidine .
NORnicotine : nor- here means that its missing a methyl group (CH3).
The damages and health effect are well known, starts with the nicotine which is
used as insecticide and it’s more stable in its sulphate form and can be used
out door ,it’s used in the agriculture .
As we mentioned in previous lectures the pyridien itself is used as indoor
insecticide because it gets degraded fast “not stable” .
In closed places like greenhouses, you can use the nicotine , just leave an open
bottle of nicotine and it will be enough to kill insects, but in open places you
should use its sulphate form as it’s more stable.
The lethal dose is ≈ 100 mg you can obtain that from smoking 5 cigarrates but
because the smoker exhales it he doesn’t get the whole amount so it won’t kill
IMMEDIATELY (but it will kill you eventually!!)
Tobacco has more than 3000 compounds in it, depending on the sensitivity of
the GCLS device used to indicate them , divided into 2 groups :
Particulate & gaseous (volatile)
The 3000 compounds are components of the tar! Which is the polycyclic
aromatic hydrocarbon , the most cancerous one!

Biosynthetic origins of tobacco alkaloids :
Heterocyclic structure found in the Nicotina tabacum alkaloids :
Pyridine
Piperidine
Pyrrolidine
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Now the pyridine is formed from the nicotinic acid which is formed by the
aspartic acid the pyridine can be converted easily into piperidine but that’s not
what happens in nature it’s more complicated to form the piperidine and use it
to form the anabasine .
Instead of L-aspartic acid--nicotinic acid-- pyridine and conver it it to
piperidine ,what happens is that the plant uses another amino acid which is Llysine .
The pyrrolidine originate from L-ornithine .
L-lysine
L-ornithine
L-aspatic acid
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5 important amino acids are involved in the synthesis of alkaloids :
tyrosine ,alanine,lysine,orthnithine,aspartic acid
3 of them are alphatic and 2 are aromatic
And then the condensation between the pyridine and pyrrolidine to form
nicotine and nornicotine and condensation of pyridine with piperidine to
form anabasine .

Tropane alkaloids :
Are also a very important as antispasmodic and anesthetic they are distributed
in few families :
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1-Solanaceae: Atropa bellladona , Datura stramonim, Hyoscyamus niger,
H.muticus , Withania somnifera .
2-Erythroxylaceae: Erythroxylum coca.
Again different isoisermism of tropane alkaloids their structure are not very
complex because the nucleus of its alkaloid tropane is composed of 2 rings
structure :piperidine+pyrrolidine and what is important that two carbons and
N are common to the rings of the piperidine and pyrrolidine ; you can write the
structure in different ways :
All tropane alkaloids have a methyl group unless they are NOR-tropanes
The biosynthesis , nothing new in this case for the formation of piperidine ring.
But here we are using acetoacetate (small carbons) in order to complete the
carbons of the tropane ring and all the carbons of the 4 acetylacetate is used
for the formation of the Coca alkaloids and all the carbons of the 3
acetylacetate fused for the formation of the Solanaceae alkaloids .
The Coca and Solanaceae alkaloids are ester alkaloids and to form an ester
alkaloid we need an alchohol moiety and an acid moiety .in fact these
heterocyclic structures which are occurring in 2 stereoisomers has a hydroxyl
group which is always attached to the carbon no.3 of the tropane nucleus ,this
alcoholic hydroxyl group occur as an α or β ,the compound that has an α is
called α-tropine and the one that has the β is called pseudotropine ( β-tropine).
Example is the tropanol :
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The α configuration attached to C no.3 is α-tropanol which occurs primaly in
the Solanaceae alkaloids and the β form is pseudotropanol .
Done by : Ghayda’ haddad
Best wishes 
Sheet no. 25 : this is the 2nd part = sheet # 25 dr.
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Plz refer to the dr’s sheet for the structures.

Acid moieties in natural and semisynthetic alkaloids :
In the case of Solanaceae, the acid moiety is tropic acid which possess an
asymmetric carbon so we’ll except to have an L- and D- configuration of the
tropic acid, and keep in mind they occur as a racemic mixture.
The biologically active tropic acid is the L-tropic acid this is why we keep saying
L-hyoscyamin and so on to indicate the precursor of it which is the L-tropic
acid, hyoscyamin is racemized to atropine ( atropine as racemate of D and L
isomer) , when we use atropine, we have to use the double dose of hyoscyamin
to achieve the same effect .
Atropine acid and apoatropine , (the prefix apo- is based on the prefix asometimes), and here it means losing an h2O molecule so (atropine – h2O =
apo-atropine).
The synthetic available marketed products are based on Mandelic acid
(homatropine).

Tropane alkaloids/ester formation :
These alkaloids as mentioned before are occurring in their ester form ( because
of the esterification of -OH group on carbon number 3 in case of tropanol with
the carboxyl group in case of the tropic acid
There are some other alcoholic moieties isolated such as alcoholic hyoscyamine
= scopolamine; it has an epoxy group between carbon no.6 and no.7, in its
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biosynthesis an O is introduced to carbon no.6 ,with the presence of the
necessary enzymes,6-hydroxy tropanol will be converted to 6,7-epoxytropine
which is termed as Scopine and with the addition of tropic acid it will be
converted to Scopolamine .
The important plants of tropane alkaloids have been mentioned before : Atropa
belladonna ….. .

Atropine :pharmacological properties/uses:
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Plz refere to ur sheet to memorize them
Alkaloids of atropine and related substances have been isolated as an
important anticholinergic substances , the difference between atropine and
scopolamine is that later is classified as an CNS depressant while atropine and
hyoscyamine are stimulants but other than that ,they posse the same
activities.
They are used to counter act the insecticides poisoning and nerve paralyzing
gases.
 Coca alkaloids :
In case of tropane alkaloid ,we said that’s it’s either produced using 3 acetyl
acetate or 4 acetate to give Ecgonine ( a tropane alkaloid) , the latter is
different, it has an additional carboxylic acid attached to carbon no.2 of the
tropane.
( the dr said carbon no.3 but I checked the internet, its carbon no 2 )
tropane + -COOH ----
In the case of Coca alkaloids ,we have 2 ester group; why? Because we have
ecgonine alkaloid which has a free –OH group which will be converted to ester
by an alcohol moiety an a free –COOH group which will be converted to ester by
an acid moiety .
The alcohol moiety is methanol to provide the –CH3 to the –COOH and convert
it to ester.
And the acid moiety is usually Benzoic acid.
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Ecgonine + -CH3 (from the methanol) --- ( carbomethoxy-ψ-tropine) + benzoic
acid-- L-cocain .
Benzoic acid can be replaced by other acids such as :
1- cinnamic acid and the formed alkaloid is cinnamyl cocain.
2- Truxillic acid(dimmeric cinnamic acidsto have α and β-truxillins .
cinnamic acid .
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truxillinic acid.

Cocain :
It’s a major alkaloid in Erythroxylum coca .
In the group of secondary metabolite of the tropane alkaloid ,two important
ones are mentioned :
1- The one used as anticholinergic .
2- the local anesthetic (Cocain), it’s advantage that until now it is not overcome
by any
synthetic local anesthetic because the cocain form a
vasoconstriction effect when used topically (in ophthalmic preparation for
example) while synthetic doesn’t! , so when we use a synthetic local
anesthetic we have to add a vasoconstrictive agent . we need the
vasconstriction effect to eliminate the sweating from the surrounding tissue
.
until 1910 cocain was legal in the coca-cola ! but then they started to use
different species of the coca that doesn’t contain cocain .
FINAL NOTE : please refer to the dr slide sheet no.25 because I wrote an
explanation of the slides and what extra things the dr said .you have to read
what’s there .
BEST WISHES 
Done by : Ghayda’ Haddad.
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