Ornithine and Lysine Alkaloids & Drugs

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Ornithine and Lysine Alkaloids & Drugs

• Ornithine.. a. Tropane Alkaloids

• -Folia Stramonii • -Folia Hyoscyami

• -Herba ve Radix Belladonnae • -Duboisia myoporoides • -Withania Somnifera

• -Atropinum

• -Folia Cocae

• -Pyridine and Piperidine Alkaloids

• -Folia Nicotianae

• -Nicotine and derivatives •

• -Lysine... b. Pyrolizidine Alkaloids

• -Herba Lobeliae

• -Cortex Radicis granatii

• c. Phenyl alanine, Tyrosine and dihydroalanine derivatives

• -Herba Ephedrae

• -Catha

• -Anona scuomosa

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Tropane alkaloids

N CH₃ _H

N

TROPANE NORTROPANE

N-methyl pyrolidine+ piperidine Pyrolidine+Piperidine

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*Tropane or nortropanol ring carries 1,2/3 –OH groups

and esterifies with acids.

*Also some of them carry epoxy group.

1-Monohydroxy Alkamine and esthers

2-Dihydroxy Alkamine and esthers

3-Trihydroxy Alkamine and esthers

4-Epoxytropanole esthers

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Tropane alkaloids

1-Monohydroxy Alkamine and esthers

Contain Tropanol (trans), Pseudotropanol (cis) and

Nor-tropanol rings.

N CH3

H

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•Tropanol + atropic acid

Atropamin

•Tropanol + veratric acid

Konvolamin

•Tropanol + 2-OH-3-Phenyl Propionic acid Littorin

•Tropanol + vanillic acid

Fillabin

•Tropanol + asetic acid

•Tropanol + propionic acid

•Tropanol + butyric acid

•Tropanol + benzoic acid

•Tropanol + izobutyric acid

•Tropanol + izovalerianic acid

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Tropic acid esthers

Optically active structures

(l) tropic acid + tropanol  Hyoscyamine (l)

(dl) tropic acid + tropanol ->> Atropine (dl)

Tropanol esthers; parasympatholytic and midriatic activity.

N CH3 H OH H C CH₂OH HOOC

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b-Pseudotropanol and Ecgonine Esthers

• Pseudo-Tropanol + benzoic acid   Tropacocaine • Pseudo-Tropanol + tiglic acid  Tigloidine

• Ecgonine + Methanol + benzoic acid   Cocaine

Ecgonine-metyl esther +sinnamic A.  Sinnamyl Cocaine

Ecgonine-metyl esther +truxillic A.  -Truxilline

Ecgonine-metyl esther +isotruxillic A.  -Truxilline

N CH3

OH

H

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c-Nortropanol Esthers

• Nor-Tropanol + l-tropic acid  norhyoscyamine • Nor-Tropanol + 3-metyl butyric acid poroidine

• Nor-Tropanol + 2-metyl butyric acid  isoporoidine • Nor-Tropanol + veratric acid   convolvine

H N

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2-Dihydroxy Alkamine Esthers

• Dihydroxytropan + 3-methylbutyric acid Valeroidine • Duboisia myoporoides • Datura sanguinea N OH HO CH₃

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3-Trihydroxy Alkamine Esthers

• Trihydroxytropan (Teloidin) + Tiglic acid Meteloidine • Datura ferox • Datura innoxia N OH CH₃ HO HO

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4-Epoxytropanol Esthers

• Scopanole + l-tropic acid  Hyoscine

• Scopanole + dl-tropic asid   Scopolamine

N

O

CH₃

OH

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General features of tropan alkaloids

• Tropan alkaloitlerinin genel özellikleri

• Interacts with general alkaloid reagents such as Mayer, Dragendorff. • Atropine, hyoscyamine and scopolamine have strong mydriatic activity. • Cocaine (pseudo-tropanol) has short mydriasis time.

• Vitali-Morin Reaction: The Vitali Morin is a specific example of the well known colour reaction between acetone and aromatic nitro compounds in the presence of sodium hydroxide. In this reaction dinitro compounds generally give a purplish-red colour, whereas trinitro compounds give a blood-red colour.

• Powdered drug + base   Organic solvent  (Evaporate) residue+ conc. Nitric acid  acetone+ KOH in methanol  Red-Blue

• Cocaine does not give Vitali Morin reaction. It can be tested by Rathenasinkam’s Reaction.

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Identification of Tropan Alkaloids

-Paper chromatography -TLC

Quantification;

Titrimetric: Alkaloids are taken to the ether in NH3 media, then ether evaporated titrate with 0.1 N HCl.

Colorimetric:

-Vitali-Morin Reaction

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Tropan Alkaloids

• Many physiological activity.

• Relaxes the smooth muscles • Dilates pupil

• Dilates blood vessels

• Increases the body temperature • Stops pain, gives some sleep

• First stimulates nervous system, then inhibits • Some of them induces halusinogenic activity

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The usage of tropane alkaloids

-To dilate the pupil

-As an antidote especially for morphine and lead poisining

-Prepare for anestesia

-Antiemetic

-Asthma crisis

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Drugs containing tropan alkaloids

• Herba ve Radix Belladonnae

• Folia Hyoscyami-Folia Stramoni

• Duboisia myoporoides

• Radix Mandragorae

• Withania somnifera

• Folia Cocae

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Duboisia myoporpides

• Grows naturally in Australia, 2-12 m tree.

• Solanaceae family plant.

• To obtain scopolamine from the leaves. Also poroidine, isoporoidine, norhyoscyamine.

• 3 species growing in Australia.

• D. leichardtii is a source plant for tropan alkaloids.

• D. hopwoodii carries nicotine and similars.

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• D. myoporoides and D. leichardtii grows in the east coasts of Australia; D. hopwoodii grows in the West and Inner Australia. • Mainly used for obtaining hyoscyamine and scopolamine. 1-3%

alkaloid. Leaves can be picked up easily twice in a year. Approximately 1200 tones of leaves are exported to European countries like Germany, Switzerland and also to Japan.

• There are some patent studies on obtaining hyoscyamine and

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Radix Mandragorae, Mandrake

Mandragora officinarum var. vernalis (green-white

flowers) (Solanaceae)

M. officinarum var. autumnalis (pale purple flower)

Mediterranean plant.

Fruits are yellow-orange, sometimes mixed with some edible fruits so that some toxication events reported.

Unique radix which looks like man. Roots carries 0.4% alkaloids. (Atropine, scopolamine, hyoscyamine, cuscohygrine)

Drug; sedative, narcotic and analgesic.

Mystic plant, in thge past used in religious anniversaries.

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The only anesthetic material used in the operations in the middle age.

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• Ecballium elatarium or Tamus communis roots are

sold as Radix Mandragorae in Turkey, but they do not

contain alkaloids.

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• Small trees or shrubs. Grows aproximately to 2m. Native to South America.

• Cultivated for long years, and leaves are picked up three times in a year (March, June and November).

Folia Cocae

Erythroxylum; red tree. E. coca (Bolivian Coca)

E. truxillense (Peru / Truksillo Coca)

Different type of E. truxillense (Java Coca)

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Coca; tree is called as Coca in Spain. Truksillo is a harbour city in Peru.

Peru and Bolivya produce Coca leaves for medicine industry legally with international pacts. In the same time these two countries are the illegal source of Coca leaves and Cocain.

Plant is cultivated at an altitude of 500-2000m. 25% of the cultivated plant was used by native public. 2% is used for medicine industry. The rest is for illegal purposes.

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The Europeans meet with the Coca leaves in 1688, and cocain was isolated in 1860.

Bolivian Coca leaves: Short stalk, oval, 2.5-7.5 height; 1.5-4 cm width; leaf leathery, greenish brown, margins entire.

Peru/Truksillo Coca leaves: E. truxillense

Pale green colour, easily fragile, lamina 1.6-5 cm length

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Anatomic features

• F. Cocae; simple crystals near veins in the mesophyll of leaf.

• Wide spaces between cells in spongy parenchyma. Stoma and papil exist in lower epiderm.

• Stoma has two neighbour cells, and the common wall is not significant, stoma is in the middle of two cells.

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• Leaves contain 0.7- 1.5% alkaloid. • Cocaine, cinnamyl cocaine and

truxilline are the main alkaloids.

• Methyl salisilate is the volatile constituent and composes the 13.6 of the essential oil.

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Before obtaining Cociane from the leaves, Coca pasta is

prepared in Columbia.

100-200 kg leaves produce 1 kg pasta.

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• Cocaine was isolated in 1860.

• Coca is Inka’s holy plant.

• Koller determied the local anesthetic effect.

• Coca leaves contain 3 types of alkaloids.

Ecgonine derivatives (cocaine, cinnamyl cocaine,



and



-truxilline)

• Tropine derivatives (Tropa-cocaine, Valerine)

• Hygrine derivatives (Hygrine ve cuscohygrine)

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• 30-50% of Coca leaf is cocaine.

• Native South Americans chew this leaf to stop hunger

and thirst. This effect is due to the local anesthetic

activity on the stomach mucosa. Also used for toothache.

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Obtained from leaves of Erythroxylum coca varieties.

Also semisynthetically obtained from ecgonine derivatives. Cocaine is a methyl esther of benzoyl ecgonine.

Hydrolization products are ecgonine + benzoic acid and methanol. Cinnamyl cocaine; Ecgonine + cinnamic acid and methanol

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Cocaine is obtained by different patented techniques in large scale.

Cocaine is a strong stimulant, and has a strong addiction potential. Decreases eating and sleeping activities.

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Cocaine HCl

HCL salt of Cocaine. White or clourless crystals or in powder form.

Used to stop strong pains of cancer patients together with morphine and methadone. (Brompton Coctail)

Nearly 6,5 million people are using Cocaine in USA. (i.v. or subcutaneus injection or base cocaine).

Base Cocaine is volatile at 98 C, while HCl salt is volatile at 195 C.

Cocaine inhalation starts quickly stimulation and euphoria.

«Crack»is the version addition with water and Na bicarbonate or amonium bicarbonate. Effective afer 10 secons of consumption.

In operative sciences cocaine was used as local anesthetic as 10% solutions in ear nose operations.

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Addiction

Cocaine addiction is similar to amphetamine addiction.

Euphoric effect is stronger than the other psycoactive drugs

like eroin.

Paranoid symptoms, agressive behaviour, antisocial

behaviour.

Very strong psycological addiction occurs.

No tolerence or physically addition occur.

No deficienct syndrome.

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Folia Stramoni; Stramonium Leaf

Datura stramonium; annual plant with many branched 5-7 parted leaves each

15-25 cm length in blue-green color. Lower surface is glandulary. Fruit is a septisid capsua.

Glandular hair in the epiderm has short stalk with multi cell head (Solanaceae type). Ca oxalate crystals (druse) exist in the mesophyll.

Dried leaves or sometimes leaves with flowers of Datura stramonium varieties (Solanaceae).

Drug must contain more than 0,25% in terms of hyoscyamine.

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• Datura (Datura stramonium L.), Datura ferox and Datura metel are some species.

• Datura gows naturally in Turkey.

• Total alkaloid amount in the leaves is 0,20-0,45%. l-hyoscyamine (2/3) and scopolamine (1/3) are the main alkaloids. Atropine also exists in the plant due to the racemization of hyoscyamine.

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It is cultivated in USA and in some European countries.

Germany is the leader country in Datura production,

alkaloid amount is increased to 2% with research and

development studies.

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Datura stramonium; antispazmodic, pain killer and narcotic due

to hyoscyamine. Like Belladon leaf it dilates pupil and CNS

sedative.

It can be used in similar doses with belladon leaf.

It can be used like a cigarette in spasmodic asthma.

The whole plant contain atropine and scopolamine. The plant can

be used as tea and consumed as cigarette. The users generally

don’t remember what they do after usage and halusinogenic effect

occurs.

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Herba Hyoscyami; Henbane

Dried leaves or sometimes leaves with

flowers

of

Hyoscyamus

niger

(Solanaceae)

Drug must contain more than 0,05 % in

terms of hyoscyamine.

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Plant has one or two years of varieties. One year variety is 30-50 cm with sticky leaves, two year varieties are nealy 80 cm.

Mostly two year varieties are cultivated because of more leaves.

Fruit is a pixidium. The leaves used for medicinal purpose are sessile and reaches to 25 cm length with 5-7 cm width. Gray-green colour leaves have deep unequal lobes. There are mant hairs in both sides of the sticky leaf. Trichomes are onelines and composed of many cells. In mesophyll simple crystals and twin crystals occur.

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Similar but weak biological activities occurs compared

with Belladon ve Stramonium. More scopolamine content

is important for brain activities.

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• Hyoscyamus niger leaves generaly contain 0.045-0.14%

alkaloid. Major alkaloids are hyoscyamine and scopolamine.

• Usage:

sedative and analgesic.

Especially for urinary sytem

pain. Shoul be used for Parkinson’s to reduce the tremors.

• Internally used for asthma treatment and menier syndrom.

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• H. muticus herb is used also for medicinal purposes. This plant is

naturally growing in Africa and Egypt and contain 0.5-1%

alkaloid.

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Herba Belladonnae-Deadly nightshade

Dried leaves or sometimes leaves with flowers of Atropa

belladonna (Solanaceae) Drug must contain more than

0,30 % alkaloid in terms of hyoscyamine.

Naturally grows in Europe and Asia, perenial plant.

Used for medicinal purposes for years, physcoactive and toxic plant. Dilates pupil.

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A. belladonna grows naturally in Europe, Anatolia and Iran (1-1.5 m height). It

has strong roots. Leaves have stalks, oval, with entire margin. Lower surface has hairs.