WELCOME

CONTENTS
COUMARINS
CLASSIFICATION PSORALEN XANTHOTOXIN REFERNCES

COUMARINS
Coumarin (2H-chromen-2one) is a fragrant organic chemical compound in the benzopyrone chemical class, which is a colorless crystalline substance in its standard state It is found naturally in many plants Families : umbelliferae, rutaceae, leguminaceae,etc Carribean word : coumarou

CLASSIFICATION
1. Simple coumarins, such as coumarin itself and dihydrocoumarin,

coumarin

dihydroxycoumarin

2.Furocoumarins are formed in result of furan ring and coumarin condensation in 6,7 positions (psoralen-derivatives) or 7,8 (angelicin-derivatives). Substitutes may occur within any of these rings

psoralen

angelicin

3. Pyranocoumarins are result of condensation of coumarin with 22-dimethylpyrane in positions 5,6 (dimethylxantyletin); 6,7 or 7,8 (visnadine) and may have substitutes in any of rings.

22dimethylxantyletin

visnadin

4. Benzocoumarins containing benzyl ring condensed with coumarin in 3,4 positions occur Anacardiaceae and Rosaceae. Hy droxyderivative of 3,4-benzocoumarin is a structural component of ellagic acid.

3,4-benzocoumarin-hydroxy-derivative

PSORALEN
Synonym: Ficusin Parent compound in the family of furanocoumarins Umbeliferon derivative Linear furanocoumrin

BIOLOGICAL SOURCE
Dried ripe fruits of psoralea corylifolia Family :Leguminosae Content of the fruit: Psoralen Isopsoralen It is present up to 3-4 % in the fruit

PSORALEA DERIVATIVES :
imperatoxin

xanthotoxin
bergapten isomer

: angelicin

SOLUBILITY:
Very soluble in chloroform Less soluble in alcohol Sparingly soluble in ether Insoluble in petroleum ether

STRUCTURE

7H-furo[3,2, benzopyran-7-one
Molecular formula :C11H6O3

CONSTITUTION
Structure of psoralen is deduced by using its degradation reaction It exhibits normal reactions of lactone of coumarin such as ring opening by alkali to give coumarinic acid or coumaric acid derivatives potassium permanganate causes oxidation of furan ring other oxidation produce furan 2,3dicarboxylic acid

ISOLATION
Dried fruits of Psoralea corylifolea
To remove essential oils &resinous matter present on outer coat

Coarse powder

Defatted with petroleum ether

Dried the marc

Extracted with methanol

Methanolic extract (psoralen +other coumarins +flavanoids)

Concentrate & dry Chromatographed on silica gel plate Psoralen in first few fraction Concentrate to yield psoralen Crystallised from ethanol or solvent ether

Chloroform as eluent

IDENTIFICATION TESTS

1mg of psoralen in 5ml of ethanol+3 parts of propylene glycol+43 parts of water Uv light Blue fluoresence

1mg psoralen in 2ml ethanol+2 drops of Uv 0.1M NaOH Emits yellow light flourescence

1mg of Psoralen in1ml of methanol

Spotted on silicagel-G plates

Plates are eluted in benzene:chloroform (98:2)

Psoralen shows blue fluracent spot with Rf value 0.25

Dried plates observed under UV light

USES
In PUVA treatment for skin disease Psoriasis eczema vitiligo Recommended in the treatment of alopecia Psoralen is a mutagen & is used in molecular biology research Tannin activator in sun screens

SYNTHESIS
H Guttermann Koch reacion CO, HCl O OH CuCl ,AlCl
3

O O OH

7-hydroxy derivative of 2,3-dihydrobenzofuran

2+

(CH 3CO) 2O

CH 3COONa Perkin Condensation

Pd O psoralen O O

O dehydrogenation

BIOSYNTHESIS
CH3 H3C HO O Um belllif erone O OP P H3C HO O Demethylsuberosin NADP H O CH3

attack of DM AP P

O2

O2 NADP H O P soralen O2 O O NADP H O O Marmesin O

O OC H O O Angelicin O
3

Xanthotoxin or Methoxsalen is extracted from Ammi majus, a plant of the family Umbelliferae. It modifies the way skin cells receive the UV radiation. AMMI MAJUS - Bishops flower, Queen Annes Lace Also known as Bishopsweed, Bishops weed, Bullwort, Greater ammi, Ladys lace, Laceflowe

Introduction contd
A tall plant originating in the Nile River Valley which has large, rounded, 10-15 cm flower heads made up of hundreds of tiny, snow-white florets. It is cultivated in North India also. The Seed of the plant contains Xanthotoxin

Chemistry
Chemically, methoxsalen belongs to a class of organic natural molecules known as furanocoumarins. They consist of coumarin annulated with furan. Xanthotoxin is 8methoxy psoralen or 8-methoxy 3,2-6,7 furocoumarin.

Chemistry contd

O OCH3
XANTHOTOXIN

Chemistry contd

O CH3

O
COUMARIN

BERGAPTEN

O O ANGELICIN

PSORALEN

Extraction and Purification

The pulverised coarse powder of the seed is used for extraction with n-hexane.

Extraction is effected in 2-3 hrs and 3-4 washings are done.

All the washings are combined and the solvent is distilled off. The separated solid is dried and de alkylated using HCl and methanol.

Extraction and Purification contd

The de alkylated material contains Xanthotoxol and Xanthotoxin

The de alkylated material is refluxed with benzene for 2 hrs and cooled to room temp. Xanthotoxol is separated

Xanthotoxin is crystallised from the filtrate at 10-150C.

Testing methods
HPTLC
Mobile phase: Acetonitrile in water (35ml in 100ml solution)

Detector wavelength: 254 nm

Flow rate: 1.5ml/minute

SYNTHESIS

Synthesis contd

Synthesis contd

Synthesis contd
The activation of dimethylallyl pyrophosphate (DMAPP), produced via the mevalonate pathway, to form a carbo-cation via the cleavage of the diphosphates. Once activated, the enzyme umbelliferone 6prenyltransferase catalyzes a C-alkylation between DMAPP and umbelliferone at the activated position ortho to the phenol, yielding demethylsuberosin. This is then followed by a hydroxylation catalyzed by the enzyme marmesin synthase to yield marmesin. Another hydroxylation is catalyzed by psoralen synthase to yield psoralen. A third hydroxylation by the enzyme psoralen 8-monooxygenase yields xanthotoxol which is followed by a methylation via the enzyme xanthotoxol O-methyltransferase and S-adenosyl

BIOLOGICAL ACTIONS
Photosensitisation effect: when irradiated to long wave length UV radiation Killing bacteria: upon irradiation Formation of mutants: Mutagenic effect is seen in E Coli and Sarcina lutea Inactivation of tumour cells Inactivation of viruses

Properties and Uses

Used to treat psoriasis, eczema, vitiligo, and some cutaneous Lymphomas in conjunction with exposing the skin to sunlight. Tonic, carminative and diuretic Relaxes smooth muscles Useful in kidney calculi and for angina pectoris In formulations of sun-tan lotions To increase the tolerance of sunlight

REFERNCES
Pharmacognosy and pharmacobiotechnology by Ashutoshkar, revised expanded 2nd edition Plant biosynthesis by Dr.S.S.Khadabadi ,S.L.Deore ,B.A.Baviskar Pharmacognosy &phytochemistry by Vinod.D.Rangari ,volume 2