Alkaloid turunan Tryptophan

Alkaloid turunan Tryptophan

Alkaloid kelompok ini mendapatkan perhatian khusus para ahli selama 2 dekade terakhir. Hal disebabkan oleh bioaktifitas dan struktur kimia khususnya masalah biosintesis, stereokimia dan tantangan total sintesis yang sangat beragam dan kompleks. Kelompok alkaloid ini banyak juga yang memiliki rantai/gugus samping yang biosintesisnya tidak sederhana. Kelompok alkaloid ini banyak ditemukan pada famili Apocynaceae, Rubiaceae, Solanaceae dan Loganiaceae

Yang termasuk alkaloid Tropan

Atropin Hyosiamin Scopolamin Cocain

Alkaloid tropan termasuk pada true allkaloid Alkaloid ini memiliki efek fisiologis, dimana dikenal sebagai bahan yang toksik (antagonis reseptor muskarinik)

Biosintesis Indol dan tryptophan

IAA

Alkaloid indol

Hyoscyamus niger Solanaceae

Definition: Hyoscyamus leaf consists of the dried leaves or dried leaves and flowering tops of Hyoscyamus niger. It should contain at least 0.05% alkaloids hyoscyamine. Common names: Henbane

Tropane Alkaloids
Derived from tropine and consist of mandelic, tropic or benzoic acid esters of tropine. Are very closely related to each other All have pronounced physiological actions.
Natural alkaloids include Hyoscyamine Hyoscine Atropine Cocaine The above mentioned alkaloids occur within the Solanaceae family (except cocaine from Erythroxylaceae family)

Atropine & Hyoscine

Have the same structure differ only in their optical activity. Also have different physiological actions Atropine deadly nightshade, Atropa belladonna: dilates eye pupils, decreases sweating, produces stomach acid and saliva & relaxes smooth muscle (asthma and colic). Hyoscine black henbane, Hyoscyamus niger: Limited influence on the CNS. Sedative Cocaine: Narcotic properties & local anaesthetic action (e.g. used in eye drops).

Hyoscine

Datura stramonium Solanaceae

Definition: Stramonium Leaf consists of the dried leaves or dried leaves and flowering tops of Datura stramonium. The drug should contain at least 0.25% alkaloids calculated as hyoscyamine.

Common names: Stramonium leaf, Thornapple, Jimson or Jamestown weed

Datura stramonium Constituents

Main (Tropane) Alkaloids * Hyoscyamine-Hyoscine (2:1) Younger plants: hyoscine predominant alkaloid Also contains Atropine Larger stems contain little alkaloid, and drug should contain no more than 3% of stems with a diameter >5mm

Uses of Datura

stramonium

Atropine: Stimulant on CNS Depresses nerve endings on the secretory glands and smooth muscle

Hyoscine: lacks CNS stimulant action of atropine Sedative motion sickness

Atropine & Hyoscine: used in opthalmic practice to dilate the pupil of the eye.

Hyoscyamus niger Constituents

Tropane Alkaloids Mainly Hyoscyamine Hyoscine (main constituent)

Hyoscyamus niger Allied

Drugs
Hyoscyamus albus (petiolate stem-leaves and pale yellow, nonveined petals bottom left). Hyosycamus muticus (top right) Hyoscyamus pusillus Hyoscyamus aureus Hyoscyamus reticulatus (Indian henbane bottom right)

Hyoscyamus niger - Uses

Resembles belladonna and stramonium in action only weaker. Higher hyoscine content less likely to cause cerebral stimulation .
Used to relieve spasm of the urinary tract

Atropa belladonna Solanaceae

Definition: Belladonna herb consists of the dried leaves and flowering tops of Atropa belladonna, containing at least 0.3% alkaloids (hyoscyamine). Should not contain >3% stem >5mm in diameter. USP also allows A. acuminata in the Belladonna Leaf monograph.

Atropa belladonna Constituents

Main (Tropane) alkaloid Hyoscyamine
Also contains Scopoletin Calcium oxalate

Atropa belladonna - Uses

Used as a sedative To stop bodily secretions (e.g. saliva) Root preparations are used externally

Pyridine Alkaloids
Also referred to as Pyrrolizidine alkaloids Include Lobeline (Lobelia herb) respiratory stimulant Used in asthma preparations. Nicotine (Nicotiana tabacum and other Nicotina spp) toxic used as an insecticide

Lobeline

Lobelia inflataDefinition: Lobelia herb consists of the dried aerial parts of Lobelia inflata.
Common Names: Lobelia, Indian Tobacco) History: Traditionally used by the Native Americans for asthma.

Capmanulaceae

Lobelia inflata
Constituents
Contains Pyrrolizidine Alkaloids Most important Lobeline
Also Lobelidine Lobelanine Isolobelanine

Lobelia inflata - Uses

Asthma Chronic bronchitis Anti-smoking preparations

Injection of lobeline hydrochloride is used in the resuscitation of newborn infants.

Caution: Toxic doses the herb has a paralytic effect.

Beberapa alkaloid sederhana turunan tryptophan

R=H, Psilosin R=OPO3H2., Psilosibin Ditemukan pada jamur Psilocybe baeocystis Dikenal juga sebagai magic mushrooms

Physostigmin, Ditemukan pada tumbuhan Physostigma venenosum Dikenal dengan bioaktifitas sebagai reversible choline esterase inbhibitor, racun panah Alkaloid b-carbolin Mis. R=H, Harman R=OH. Harmine Ditemukan pada biji Peganum harmala Memiliki aktifitas halucinogenic narcotic and anticarcinogenic

Alkaloid Indol
Mrpk alkaloid yang mengandung cincin indol N
Alkaloid ini bisa ditemukan pada Ergot & Nux vomica Alkaloid ergot berdasarkan adanya asam lisergat. Nux vomica, alkaloid pentingnya strycnine & brucine

Alkaloid peptida ergot Ergot dihasilkan dari jamur Claviceps purpurea yang tumbuh pada gandum secale cereale, secale curnutum Mempunyai arti komersial penting, yang menghasilkan asam lisergat Proline dan asam amino lain.
1. Ergotamine 2. Ergocristine

R1 CH3
CH(CH3)2

R2 CH2C6H5
CH2C6H5

3. Ergokryptine
4. Ergocornine 5. Ergosine

CH(CH3)2
CH(CH3)2 CH3

CH2CH(CH3)2
CH(CH3)2 CH2CH(CH3)2 CH2CH(CH3)2, 9,10a-H2

6. Dihydroergosine CH3

Bioaktifitas utama : vasokonstriksi dan uterotonik

Alkaloid indol monoterpenoid al:

Alkaloid Asal Aktifitas farmakologis

1.Ajmalicine 2.Ajmalin 3.Camptothecine 4.Deserpidine 5.Ibogaine 6.Leurocrystine 7. Quinidine 8. Reserpin 9. Strychnine 10.Vincaleucoblastine 11.Vincamine

Catharanthus roseus Hypotensive Ruwolfia sp Antiarrythmic Camptotheca acuminata Anticancer Rauwolfia canescens Hypotensives Tabernanthe iboga Psychotomimetic Catharanthus roseus Anticancer Remija sp Cardiac deppressant Rauwolfia vomitoria hypotensive Strychnos nux fomica CNS depressant Catharanthus roseus Anticancer Vinca major Hypotensives

Camptothecine, diisolasi dari Camptotheca acuminata Carcinogenic (sudah dipasarkan)

Yohimbine, dari kulit kayu Corynanthe yohimbe, juga ditemukan pada berbagai tumbuhan lain spt Rauwolfia, Amsonia, Aspidosperma, Catharanthus dll Memiliki banyak stereoisomer, dikenal memiliki efek afrodisiak

Alkaloid Rauwolfia,

Reserpin Rescinamine Desrpidin

R1 OCH3 OCH3 H

R2 3,4,5-trimetoksibenzoil 3,4,5-trimetoksisinnamoil 3,4,5-trimetoksibenzoil

Alkaloida utama Cinchona

R1
1.Cinchonine 2.Cinchonidin 3.Quinin 4.Quinidin b-OH, b H -CH=CH2 a-OH, a H, -CH=CH2 b-OH, b OH -CH=CH2 a-OH, a-H, -CH=CH2

R2
H H OCH3 OCH3

Quinidin sampai sekarang masih merupakan obat penting untuk cardiac arrithmia. Ekstrak kulit kina Sampai sekarang masih banyak \ digunakan sebagai tonik

11

Alkaloidfa Strychnos Merupakan alkaloida yang ditakuti karena sangat beracun. Memberikan tantangan yang khusus bagi ahli kimia karena struktur yanng kompleks 11-OCH3 (brucine)

Alkaloida Catharanthus Telah berhasil diidentifikasi lebih dari 90 jenis Vincaleucoblastine (VLB), Leurocrystine (VCR) , VCR human cancer VLB hodgkin disease R = CH3 (1 g/ton) R = CHO ( 20 mg/ton)

CH3O

Isoprenoid alkalod

Alkaloid turunan isoprenoid

Alkaloid steroid mis. Alkaloid Solanum

Alkaloid monoterpenoid. (turunan loganin dan secologanin) Alkaloid sesquiterpenoid Alkaloid Diterpenoid Alkaloid Daphniphyllum
5 6

Tomatidin, R = H Solasodine, R = H, D 5-6 Tomatin , R = b-lycotetrose

Bukittinggine (Sapium baccatum, nyatua batu)

Alkaloid Gol. sisa

Alkaloid Purin
Koffein Theophylline Theobromine CH3 CH3 H CH3 CH3 CH3 CH3 H CH3

Alkaloid Gol. sisa

Macrocyclic peptide alkaloids

Mushrooms peptide alkaloids

Saxitoksin