Farmakognosi

Komposisi nilai

• Kuis : 20%

• Tugas : 50%

• UAS : 30%

Materi Kuliah

• Fenilpropanoid

• Flavonoid

• Alkaloid : 2

• Terpenoid

• Zat Pahit

Penugasan

• Membuat makalah dan presentasi terkait produk yg mengandung metabolit sekunder tsb.

• Batasan tugas : profil produk (nama produk, foto, komposisi, dosis, cara penggunaan, manfaat/khasiat), kandungan metabolit yg terkandung, sumber tumbuhan dan cara isolasi metabolit tsb, mekanisme aksi metabolit dalam menimbulkan khasiat (bila khasiatnya banyak, pilih 1 khasiat yg lengkap mekanisme aksinya, min. Diperoleh dari 5 jurnal)

• Makalah lengkap : cover, daftar isi, isi, kesimpulan, daftar pustaka

Fenilpropanoid

Klasifikasi fenilpropan

• Fenilpropanoid (C6-C3)

• Flavonoid (C6-C3-C6)

Klasifikasi fenilpropanoid

• Asam hidroksisinamat

• Fenilpropena

• Kumarin

• Fenilpropanoid pendek

• Turunan bifenilpropenoid

• Fenilpropanoid BM tinggi

biphenylpropane

phenylpropane

Asam hidroksisinamat

• Asam para-kumarat

• Asam kafeat

• Asam ferulat

• Asam sinapat

Asam para-kumarat

• Sinonim : asam p-hidroksisinamat

• Sumber biologis : Lidah buaya (Aloe barbadensis Mill), Mole plant (Euphorbia lathyris L.), Apel (Malus sylvestris Mill.)

• Pemerian : berbentuk jarum dan memiliki titik lebur 210-213°C. Mudah larut dalam etanol, eter, dan air panas, sukar larut dalam air dingin, dan praktis tidak larut dalam benzen.

• Manfaat : antioksidan, menghambat pembentukan platelet (in vitro dan in vivo)

Asam Kafeat

• Sinonim : Asam 3,4-dihidroksisinamat

• Sumber biologis : Kopi (Coffea sp.), Wintergreen (Gaultheria procumbens L.), Red clover (Trifolium pratense L.)

• Pembuatan : asam kafeat pada tumbuhan hanya berada dalam bentuk terkonjugasi, misal asam klorogenat. Asam ini juga telah diisolasi dari kopi hijau dan kopi panggang

• Pemerian : bentuk kristal kuning dari larutan air pekat dan bentuk monohidrat dari larutan encer. Asam kafeat melunak pada 194°C dan mengurai pada 223-225°C. Mudah larut dalam etanol dan air panas, agak sukar larut dalam air dingin

• Uji kimia : 1. Asam kafeat berubah warna dari kuning menjadi jingga

dalam media basa 2. Asam kafeat segera membentuk metil ester (C10H10O4) yg

diperoleh sebagai kristal tak berwarna dari air (titik lebur 152-153°C)

• Manfaat : antioksidan, menghambat xantin oksidase, menghambat replikasi virus Hepatitis B (in vitro dan in vivo)

Asam ferulat

• Sinonim : asam kafeat 3-metil eter, asam 4-hidroksi-3-hidroksisinamat

• Sumber biologis : resin Asafoetida (Ferula assafoetida L.), perdu Saw palmetto (Serenoa repens (Bartel.), ranting ivy (Hedera helix L.), Pirus laricio Poir. (Abietineae)

• Pembuatan : diisolasi dari Ferula foetida Reg (Umbelliferae) dan Pirus laricio Poir. (Abietineae). Asam ferulat jg dapat disiapkan melalui interaksi vanilin, asam malonat, dan piperidin dalam piridin selama 3 minggu dan kemudian endapkan asam ferulat dengan HCl encer

• Pemerian : – Bentuk cis : minyak kuning, UVmaks (dalam etanol) :

316nm – Bentuk trans : jarum ortorombik yg diperoleh dari air,

titik leleh 174°C, UVmaks (dalam etanol) : 236 dan 322nm. Larut dalam air panas, etanol, dan etil asetat, cukup larut dalam eter, agak sukar larut dalam benzen dan PE

• Uji identifikasi : asam ferulat dengan larutan NaOH membentuk garam natrium sehingga menyebabkan kelarutannya cukup meningkat

• Kegunaan : asam ferulat digunakan sbg pengawet produk makanan, antioksidan

Asam sinapat

• Sumber biologis : daun dan ranting European mistletoe (Viscum album L.) (Loranthaceae)

• Pembuatan : hidrolisis ester kolin asam sinapat dari biji mustard hitam (Brassica nigra Koch (Cruciferae), baik dalam media asam maupun dg hidrolisis enzimatik.

• Kegunaan : 1. Asam sinapat digunakan sbg antiseptik,

antispasmodik, dan emetik 2. Asam sinapat juga digunakan pada arteriosklerosis,

stimulan jantung, kanker, hepatosis, dan hipertensi 3. Asam sinapat juga telah digunakan dalam

penanganan epilepsi, histeria, dan debilitas saraf

Fenilpropena

• Sinonim : sinamal, fenilakrolein, sinamat aldehid

• Sumber biologis : minyak kayu manis Sri Langka (Cinnamomum verum J.S Presler) (Lauraceae), balsam Peru (Myroxylon balsamum var.Pereirae (Royle) Harms (Fabaceae), cengkeh (Syzygium aromaticum (L.) Merr&Perry (Myrtaceae)

• Pembuatan : minyak kasia (Cinnamomum cassia Blume) mengandung minyak atsiri 1-2%. Minyak atsiri ini mengandung sinamaldehid 80-85% yg diisolasi melalui distilasi fraksional dalam vakum.

• Pemerian : cairan berminyak kekuningan yg memiliki bau kayu manis yg tajam. Parameter fisiknya d25

25 1,048-1,052; TD100 177,7°C; TD200 199,3°C and TD760 246°C. Sinamaldehid larut dalam 700 bagian air dan 7 bagian etanol 60%. Akan tetapi, sinamaldehid tdk bercampur dg etanol, eter, kloroform, dan minyak.

• Uji kimia : penambahan setetes larutan FeCl3 1% b/v menghasilkan warna cokelat yg khas

• Kegunaan : 1. Fenilpropena banyak digunakan pd industri

parfum 2. Fenil propena digunakan utk memberikan aroma

pada makanan dan minuman

Kumarin • Kumarin • Hidroksikumarin

– Umbelliferon – Eskuletin – Skopoletin – Dafentin – Fraksetin

• Furanokumarin – Psoralen – Metoksalen – Bergapten – Imperatorin

Kumarin

• Sinonim : asam cis-o-lakton kumarinat, kumarin, kumarinat anhidrat, kamfer biji tonka

• Sumber biologis : Biji tonka (Dipteryx odorata (Aubl) Willd), Anisi (Pimpinella anisum L.), Seledri (Apium graveolens L.)

• Pemerian : kristal kumarin memiliki lempeng ortorombik dan rektangular. Kumarin memiliki bau yg enak dan wangi mirip dg biji vanili dan rasa terbakar.

• Karakter fisika : titik leleh 68-70°C dan titik didih 297-299°C. Kumarin larut dalam etanol, kloroform, eter, minyak, dan larutan NaOH/KOH, agak sukar larut dlm air panas (1:50), sukar larut dlm air dingin (1:400)

• Kegunaan : kumarin banyak digunakan sbg pemberi aroma pada formulasi obat

Hidroksikumarin

Umbelliferon • Synonyms Hydrangin; Skimmetin. • Biological Sources Umbelliferone is present in a variety of medicinal

plants, for instance: Apium graveolens L. (Apiaceae) Celery; Dipteryx odorata (Aubl.) Willd. (Fabaceae)-Tonka Bean; Ferula sumbul Hook. (Apiaceae)-Sumbul; Lavandule angustifolia Mill. (Lamiaceae)-Lavender; Matricaria chamomilla L. (Asteraceae)-Hungarian Camomile; and Pimpinella anisum L. (Apiaceae)-Anise.

• Preparation Asafoetida contains resin (40-65%) which consits of chiefly a resin-alcohol asaresinotannol both in the free or combined form with ferulic acid, and of course, free umbelliferone is totally absent in the drug. Thus, umbelliferone is prepared by treating ferulic acid with HCl which gets converted to umbellic acid and the latter loses a molecule of water to give rise to umbelliferone

• Umbelliferone may also be obtained by distillation of resin from Umbelliferae.

• Characteristic Features It is obtained as needles from water. It develops the characteristic odour of coumarin on heating. Its mp is 225-228°C. It usually sublimes. Its solubility in water is very poor i.e., it dissolves 1 g in nearly 100 ml of boiling water. It is freely soluble in ethanol, chloroform, acetic acid and dilute alkaline solution. It is sparingly soluble in ether and the solutions exhibit a distinct blue fluorescence.

• Identification Test When 0.5 g of umbelliferone is triturated with pure sand (SiO2) and 5 ml of HCl, added 5 ml of water, filtered and to the filtrate added an equal volume of ammonia solution, it gives a beautiful blue fluorescence.

• Uses 1. It is an important ingredient in most sunscreen lotions and creams. 2. It is most importantly used as an intracellular and pH sensitive

fluorescent indicator and bloodbrain-barrier (BBB) probe.

Esculetin • Synonyms Aesculetin; Chicorigenin; 6, 7-Dihydroxy-coumarin. • Biological Source It is the aglucon of esculin and cichorlin: Esculin is

derived from two different plant sources, namely: (a) the barks of Crataegus oxycantha L. (Rosaceae)-Hawthorn; and (b) the flowers of Centarea cyanus Linn., (Compositae). It is a glucoside which upon hydrolysis gives the aglucon esculetin.

• Esculetin is also obtained from cichorlin, which is a glucoside and found to be isomeric with esculin. Cichorlin is present in the flowers of the chicory plant (Chichorium intybus L., family: Compositae).

• Uses : antioxidant, inhibitor human leukemia cell inhibitor, antiinflamation (in vivo and in vitro)

Skopoletin

• Synonyms Chrysatropic acid; Gelseminic acid; 6-Methoxyumbelliferone; β-Methylesculetin; 7-Hydroxy 6-methoxycoumarin

• Biological Sources It is the aglucone of scopolin. Scopoletin occurs in the roots of Arnica montana L. (Asteraceae)-Mountain Tobacco, Leopard’s-bane; leaves of Artemesia abrotanum L. (Asteraceae)-Southernwood, Old Man; roots and leaves of Atropa belladona L. (Solanaceae)-Belladonna, Deadly Nightshade; barks of Brunfelsia uniflorus (Phol.) D. Don. (Solanaceae)-Manaca, Manacan; fruits of Capsicum annuum L. (Solanaceae)-Chili, Sweet Peppers, Paprika; oil of the plant Chamaemelum nobile (L.) All. (Asteraceae)-Roman Comomile; English Camomile, Comomile; and roots of Withania somniferum (L.) Dunal (Solanaceae)-Ashwagandha.

• Preparation It is obtained by the hydrolysis of the glucoside scopolin i.e., 7-(β-D glucopyranosyloxy)-6-methoxy-2H-1-benzopyran-2-one as follows:

• Characteristic Features Scopoletin occurs as prisms or needles from either acetic acid or chloroform. It melts at 204°C. It is slightly soluble in water or cold ethanol and quite soluble in hot ethanol and hot glacial acetic acid. It is moderately soluble in chloroform, but practically insoluble in the non-polar solvent benzene.

• Uses : – Antioksidant, antifungal, immunomodulator, hepatoprotective

(in vitro and in vivo)

Dafentin • Synonyms 7, 8-Dihydroxycoumarin • Biological Sources It is the aglucon of daphnin. It is

obtained from the seeds and fruits of Daphne mezereum L. (Thymelaeaceae)-Mezereon; and the seeds of Euphorbia lathyris L. (Euphorbiaceae)-Mole Plant, Petroleum Plant, Caper Spurge.

• Preparation Daphentin is prepared conveniently from its glucoside known as daphnin i.e., 7, 8-dihydroxycoumarin 7-β-D-glucoside by treating the latter in three different ways, namely: (i) By boiling with dilute mineral acids; (ii) By enzymatic hydrolysis; and (iii) By sublimation as given below:

• Characteristic Features The crystals obtained from dilute ethanol has a mp 256°C (decomposes). It undergoes sublimation on heating. It is soluble in boiling water, hot dilute alcohol and hot glacial acetic acid. It is found to be sparingly soluble in ether, chloroform, and benzene.

• Identification Tests • 1. An aqueous solution of daphentin gives a

green colouration with FeCl3 solution, which turns red on the addition of sodium carbonate.

• 2. An alkaline solution of daphentin in alkali carbonate or alkali gives a yellow colour.

Fraksetin

• Synonyms 7, 8-Dihydroxy-6-methoxycoumarin.

• Biological Source It is the aglucon of fraxin. Fraxin is present in the seeds of Acsculus hippocastanum L. (Hippocastanaceae)-Horse Chestnut.

• Preparation Fraxetin is obtained by heating fraxin with dilute sulphuric acid to affect the hydrolysis of glucoside and get the desired aglucon residue as shown here under:

• Characteristic Features Fraxetin is obtained as plates from ethanol having mp 228°C. It has been observed that it turns first yellow at 150°C and subsequently brown at mp. It is soluble in 10 L of cold water, but in 300 ml of boiling water. It is somewhat more soluble in alcohol and practically insoluble in ether.

• Uses : Antioxidant, neuropotective (in vitro)

Furanokumarin

• Furanocoumarins, represent a class of relatively more complex coumarins that occur in various natural plant products. A few important members of this particular class are, namely: Psoralen; Methoxsalen; Bergapten; and Imperatorin.

Psoralen

• Synonyms Ficusin; 6-Hydroxy-5-Benzofuranacrylic acid d-lactone; Furo (3, 2-d)-coumarin.

• Biological Source Psoralen belongs to one of a group of furanocoumarins occurring naturally in more than two dozen different plant sources, for instance: Rutaceae (e.g., Bergamot, Limes, Cloves); Umbelliferae (Celery; Parsnips); Leguminosae (e.g., Psoralen coryfolia). It is also found in the Rue Oil obtained from Ruta graveolens L. (Rutaceae)-known as Rue (daun inggu). It is obtained from the leaves of Ficus carica Linn. (Moraceae)-Figs.

• Characteristic Features Psoralen crystals from ether have two sets of melting points e.g., 163-164°C and 169-179°C (Spath). It is very soluble in chloroform, less soluble in alcohol, sparingly soluble in ether and practically insoluble in petroleum ether (60-80°C).

Identification Tests • 1. Dissolve 1 mg of psoralen is 5 ml of ethanol and add to it 15 ml of

a mixture made up of 3 parts of propylene glycol, 5 parts of acetic acid and 43 parts of water. The resulting mixture on being exposed to the uv-light in a uv-chamber, gives a distinct blue-fluorescence.

• 2. When 1 mg is dissolved in 2 ml ethanol, mixed with two drops of NaOH solution (0.1 M) and the resulting solution is subjected to uv-light, it emits a yellow fluorescence.

Uses 1. It is used in the treatment of leucoderma patches. 2. Psoralens have also exhibited photosensitizing and phototoxic

effects in animals and human beings and, hence have been employed extensively in photochemotherapy for the treatment and management of vitiligo, psoriasis and mycosis fungoides.

3. It is used orally as laxative

Metoksalen

Synonyms Xanthotoxin; Meloxine; Ammoidin; Meladinine; 8-Methoxypsoralen; 8-MOP; 8-MP; Oxsoralen.

Biological Source Methoxsalen is a naturally occurring analogue of psoralen, found in various species of Rutaceae, Leguminosae, and Umbelliferae. It is obtained from the fruits of Fragara xanthoxyloides and the fruits of Ammi majus belonging to the natural order Umbelliferae. It is also found in the herb Ruta graveolens (Rutaceae).

Isolation The various steps involved are as under: 1. The A. majus fruits are dried, powdered, sieved and extracted with

petroleum ether to complete exhaustion. 2. The petroleum ether extract is filtered and concentrated to obtain a dark

green semi-crystalline solid mass (crude methoxalen) crystallizes out. 3. The residual dark-green solid mass is dissolved in minimum quantity of

ethanol and boiled over an electric water-bath for 45-60 minutes. The contents are filtered immediately and the filtrate is concentrated under vacuum. It is cooled in a refrigerator overnight when pale-green crystals separate out. The crystals of methoxsalen thus obtained are purified first by washing with boiling water and finally recrystallizing from ethyl acetate.

Characteristic Features 1. It is obtained in two forms: first—as silky needles either from hot water or benzene

+ petroleum ether; secondly—as long rhombic prisms from ethanol + ether, having mp 148°C.

2. It is odourless but has a distinct bitter taste followed by tingling sensation. 3. It has a pH 5.5. 4. Solubility Profile: It is practically insoluble in cold water; sparingly soluble in boiling

water, liquid petroleum, ether; soluble in boiling ethanol, acetone, acetic acid, vegetable fixed oils, propylene glycol, benzene; freely soluble in chloroform; and soluble in aqueous alkalies with ring cleavage, but is reconstituted upon neutralization.

Identification Tests These are as follows: 1. A few crystals of methoxsalen on being triturated with little sulphuric acid in a

porcelain dish produces an orange-yellow colour that gets changed to light green finally.

2. Wagner’s Reagent Test: Xanthotoxin gives an instant precipitate with Wagner’s Reagent (I2 + KI).

3. HNO3 Test: It gives a distinct yellow colouration with dilute HNO3, which on rendering to alkaline with KOH or NaOH, changes to crimson colour.

Uses 1. It is used extensively in the treatment of leukoderma. 2. It is employed as a pigmentation agent. 3. It is also used in the treatment of psoriasis and mycosis fungoides.

Bergapten

Synonyms Bergapten; Heraclin; Majudin; Psoraderm; 5-Methoxypsoralen; 5-MOP.

Biological Source Bergapten is the naturally occurring analogue of psoralen and an isomer of methoxsalen, mostly found in a wide variety of plants, such as: roots and fruits of Angelica archangelica L. (Apiaceae)-Angelica, Garden Angelica, European Angelica; seeds of Apium graveolens L. (Apiaceae)-Celery; leaves, stems and fruits of Petroselinum crispum (Mill.) Nym. (Apiaceae)-Parsley; Rue Oil of Ruta graveolens L. (Rutaceae)-Rue, Garden Rue, German Rue.

Preparation Bergapten was first isolated from the oil of bergamot from Citrus bergamia Risso., belonging to the natural order Aurantiodiae*. It was also isolated from Fagara xanthoxyloides Lam., belonging to family Rutaceae.**

Characteristic Features The crystals obtained from ethanol are needle-shaped having mp 188°C. It sublimes on heating. It is practically insoluble in boiling water, slightly soluble in glacial acetic acid, chloroform, benzene, and warm phenol. It is soluble in absolute ethanol (1 part in 60).

Identification Test It gives a distinct yellow-gold colouration when its solution is treated with a few drops of concentrate H2SO4.

Uses 1. It is used in photochemotherapy of psoriasis. 2. It has been used to promote tanning in suntan

preparations e.g., creams and lotions.

Imperatorin

Synonyms Ammidin; Pentosalen; Marmelosin;

Biological Sources It is obtained from the roots and fruits of Angelica archangelica L. (Apiaceae) (Angelica, Garden Angelica, European Angelica); from the roots of Imperatoria osthruthium L. (Umbelliferae); from fruit of Pastinaea sativa L. (Umbelliferae); and also in the fruits of Ammimajus (Umbelliferae). However, the seed oil of A. archangelica is said to contain upto 0.5% imperatorin.

Uses : anticonvulsant, vasodilator (in vitro and in vivo)

Isolation The various steps involved are as follows:

1. The petroleum ether mother liquor left after the separation of methoxsalen (Xanthotoxin), is concentrated under vacuo and allowed to cool in a refrigerator overnight when the crude imperatorin separates out.

2. The crude product is collected, dissolved in ether, filtered and concentrated under reduced pressure. It is kept in a refrigerator, and the crystals separating out are purified subsequently by recrystallization from ethanol.

Characteristic Features These are as given below:

1. It is obtained in two forms: First—as prisms from ether, and secondly—as long fine needles from hot water, having mp 102°C.

2. Solubility Profile: It is practically insoluble in cold water; very sparingly soluble in boiling water; freely soluble in chloroform; and soluble in benzene, ethanol, ether, petroleum, ether alkali hydroxides.

Identification Tests These are as stated below:

1. Sulphuric Acid Test: Imperatorin gives an intense deep orange colouration with a few drops of sulphuric acid which ultimately changes to brown colour.

2. Marqui’s Reagent: It gives an orange colouration with Marqui’s Reagent that rapidly changes to brown.

3. Tollen’s Reagent (Ammoniacal AgNO3): It reduces Tollen’s Reagent to produce a silver mirror.

4. Fehlings Test: It reduces Fehling’s solution to give a brick-red precipitate of cupric oxide.

5. Nitric Acid Test: It gives a distinct yellow colour on boiling with dilute HNO3, and this colour changes to purple on being treated with strong alkali e.g. NaOH or KOH.

OO

O O OHO

O O

H

O

OH

O

HO

HO

OH

O

H3CO

HO

OCH3

Sebutkan nama, golongan senyawa, dan manfaat dari struktur-struktur di bawah ini :

1 2

3 4

5 6

Fenilpropanoid Rantai Pendek

• Berbagai fenilpropanoid rantai pendek yg terdapat pada banyak herba obat biasanya diklasifikasikan menjadi 3 kelas utama yaitu :

1.Tidak memiliki rantai samping

2.Memiliki rantai samping dengan 1 atom C, dan

3.Memiliki rantai samping dengan 2 atom C

Fenilpropanoid tidak memiliki rantai samping • Katekol • Sinonim : Pirokatekol, Pirokatekin, 1,2-

dihidroksibenzen • Sumber biologis : Anandenathera peregrina

L.speg (Mimosaceae)-Niopo, Yupa; korteks Melia azedaraeh L.(Meliaceae)-Chinaberry; Rumex crispus L.(Polygonaceae)-Yellow Dock

• Pembuatan : ekstrak air dapat diperlakukan dg basa encer scr hati-hati, dan garam natrium yg dihasilkan dinetralkan utk menghasilkan katekol dari sumber tumbuhan alam

OH

OH

• Pemerian : katekol diperoleh sbg tablet atau prisma monoklinat dari toluena. Katekol biasanya mengalami perubahan warna jika terpajan udara dan cahaya.

• Karakteristik fisik: titik lebur 105°C; d 1,344; TD₇₆₀ 245,5°C. Katekol larut dlm 2,3bagian air, etanol, benzen, kloroform, dan eter, sangat larut dlm larutan air alkali dan piridin. Larutan air katekol diketahui segera berubah mjd cokelat.

• Uji identifikasi: larutkan 0,2g katekol dlm air dan tambahkan beberapa tetes larutan air FeCl₃ (0,1%b/v). Perubahan warna menjadi hijau menunjukkan adanya katekol.

• Kegunaan : 1. Katekol digunakan sbg bahan antiseptik 2. Katekol diketahui digunakan dlm fotografi 3. Katekol juga digunakan dlm pewarnaan bulu binatang

Fenilpropanoid dg rantai samping 1 atom C

COOH

benzoic acid

COOH

OH

OH

HO

Asam galat

O-D-Glukosa

OH

Salisin

OH

OCH3

O H

Vanilin

Asam Benzoat

• Sinonim : asam drasiklik, asam fenilformat, asam benzen karboksilat

• Sumber biologis : asam benzoat ditemukan dlm btk bebas dan kombinasi. Gom benzoin mengandung asam benzoat 20%, buah buni (berry) mengandung asam benzoat cukupbesar 0,05%. Minyak Cananga odorata (Lam.) Hook.f&Thoms.(Fabaceae)-Kenanga; Piper methysticum Forst.(Piperaceae)-Kava-kava