Alkaloid turunan Tryptophan

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

Biosintesis Indol dan tryptophanIAA

Alkaloid indol

Hyoscyamus niger - SolanaceaeDefinition: 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 AlkaloidsDerived from tropine and consist of mandelic, tropic or benzoic acid esters of tropine.Are very closely related to each otherAll have pronounced physiological actions.

Natural alkaloids includeHyoscyamineHyoscineAtropineCocaineThe above mentioned alkaloids occur within the Solanaceae family (except cocaine from Erythroxylaceae family)

Atropine & HyoscineHave the same structure differ only in their optical activity.Also have different physiological actionsAtropine 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. SedativeCocaine: Narcotic properties & local anaesthetic action (e.g. used in eye drops).

Hyoscine

Datura stramonium - SolanaceaeDefinition: 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 - ConstituentsMain (Tropane) Alkaloids * Hyoscyamine-Hyoscine (2:1)Younger plants: hyoscine predominant alkaloid

Also containsAtropine

Larger stems contain little alkaloid, and drug should contain no more than 3% of stems with a diameter >5mm

Uses of Datura stramoniumAtropine: Stimulant on CNSDepresses nerve endings on the secretory glands and smooth muscle

Hyoscine: lacks CNS stimulant action of atropineSedative motion sickness

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

Hyoscyamus niger - ConstituentsTropane AlkaloidsMainlyHyoscyamineHyoscine (main constituent)

Hyoscyamus niger Allied Drugs

Hyoscyamus albus (petiolate stem-leaves and pale yellow, non-veined petals bottom left).Hyosycamus muticus (top right)Hyoscyamus pusillusHyoscyamus aureusHyoscyamus reticulatus(Indian henbane bottom right)

Hyoscyamus niger - UsesResembles 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 - SolanaceaeDefinition: 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 - ConstituentsMain (Tropane) alkaloidHyoscyamine

Also contains ScopoletinCalcium oxalate

Atropa belladonna - UsesUsed as a sedativeTo stop bodily secretions (e.g. saliva)Root preparations are used externally

Pyridine AlkaloidsAlso referred to as Pyrrolizidine alkaloidsIncludeLobeline (Lobelia herb) respiratory stimulant Used in asthma preparations.Nicotine (Nicotiana tabacum and other Nicotina spp) toxic used as an insecticide

Lobeline

Lobelia inflata- CapmanulaceaeDefinition: 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.

Lobelia inflata ConstituentsContains Pyrrolizidine AlkaloidsMost importantLobeline

AlsoLobelidineLobelanineIsolobelanine

Lobelia inflata - UsesAsthmaChronic bronchitisAnti-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 tryptophanR=H, PsilosinR=OPO3H2., PsilosibinDitemukan pada jamur Psilocybe baeocystisDikenal juga sebagai magic mushroomsPhysostigmin,Ditemukan pada tumbuhan Physostigma venenosumDikenal dengan bioaktifitas sebagai reversible cholineesterase inbhibitor, racun panah Alkaloid b-carbolinMis. R=H, Harman R=OH. HarmineDitemukan pada biji Peganum harmalaMemiliki aktifitas halucinogenic narcotic and anticarcinogenic

Alkaloid IndolMrpk alkaloid yang mengandung cincin indolAlkaloid ini bisa ditemukan pada Ergot & Nux vomica Alkaloid ergot berdasarkan adanya asam lisergat. Nux vomica, alkaloid pentingnya strycnine & brucine

R1 R2Ergotamine CH3 CH2C6H5

Ergocristine CH(CH3)2 CH2C6H5

Ergokryptine CH(CH3)2 CH2CH(CH3)2

Ergocornine CH(CH3)2 CH(CH3)2

Ergosine CH3 CH2CH(CH3)2 Dihydroergosine CH3 CH2CH(CH3)2, 9,10a-H2

Bioaktifitas utama : vasokonstriksi dan uterotonik Alkaloid peptida ergotErgot dihasilkan dari jamur Claviceps purpurea yang tumbuh pada gandum secale cereale, secale curnutumMempunyai arti komersial penting, yang menghasilkan asam lisergatProline dan asam amino lain.

Alkaloid indol monoterpenoid al:Alkaloid Asal Aktifitas farmakologis

1.AjmalicineCatharanthus roseus Hypotensive2.AjmalinRuwolfia sp Antiarrythmic3.CamptothecineCamptotheca acuminata Anticancer4.DeserpidineRauwolfia canescens Hypotensives5.IbogaineTabernanthe iboga Psychotomimetic6.LeurocrystineCatharanthus roseus Anticancer7. QuinidineRemija sp Cardiac deppressant8. ReserpinRauwolfia vomitoria hypotensive9. StrychnineStrychnos nux fomica CNS depressant10.Vincaleucoblastine Catharanthus roseus Anticancer11.VincamineVinca major Hypotensives

Camptothecine, diisolasi dari Camptotheca acuminataCarcinogenic (sudah dipasarkan)Yohimbine, dari kulit kayu Corynanthe yohimbe, juga ditemukan pada berbagai tumbuhan lain spt Rauwolfia, Amsonia, Aspidosperma, Catharanthus dllMemiliki banyak stereoisomer, dikenal memiliki efek afrodisiak

Alkaloid Rauwolfia, R1R2ReserpinOCH3 3,4,5-trimetoksibenzoilRescinamineOCH3 3,4,5-trimetoksisinnamoilDesrpidinH 3,4,5-trimetoksibenzoil

Alkaloida utama Cinchona R1 R2

1.Cinchonine b-OH, b H -CH=CH2 H2.Cinchonidin a-OH, a H, -CH=CH2 H3.Quinin b-OH, b OH -CH=CH2 OCH34.Quinidin a-OH, a-H, -CH=CH2 OCH3

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

Alkaloidfa Strychnos Merupakan alkaloida yang ditakuti karena sangat beracun.Memberikan tantangan yang khusus bagi ahli kimia karena struktur yanng kompleks11-OCH3 (brucine)

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Alkaloida Catharanthus

Telah berhasil diidentifikasi lebih dari 90 jenis

Vincaleucoblastine (VLB), R = CH3 (1 g/ton)Leurocrystine (VCR) , R = CHO ( 20 mg/ton)

VCR human cancer VLB hodgkin diseaseCH3O

Isoprenoid alkalod

Alkaloid turunan isoprenoidAlkaloid monoterpenoid. (turunan loganin dan secologanin)Alkaloid sesquiterpenoidAlkaloid Diterpenoid

Alkaloid Daphniphyllum

Tomatidin, R = HSolasodine, R = H, D 5-6 Tomatin , R = b-lycotetrose5 6Alkaloid steroidmis. Alkaloid SolanumBukittinggine(Sapium baccatum, nyatua batu)

Alkaloid Gol. sisaAlkaloid PurinKoffeinCH3CH3CH3TheophyllineCH3CH3HTheobromineHCH3CH3

Alkaloid Gol. sisaMacrocyclic peptide alkaloids

Mushrooms peptide alkaloids

Saxitoksin

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