Alkaloids 1
description
Transcript of Alkaloids 1
Alkaloids 1
• Alkaloids originating from1-Capsaicinoides (Capsicum annuum [Solanaceae])Capsaicine:pungent, iritation on the skin, rubafecient in rheumatoid pain
2-Ephedrine, pseudoephedrine (Ephedra sinica)3-Cathine (Catha edulis)
CO2H
NH2
Phenylalanine
N
O
H
H3CO
HO
N
O
H
H3CO
HO OH
Capsaicin
Hydroxycapsaicin
Ephedrine
Ephedra sinica “ma huang”; Used in treatment of common cold, ↑BP and pulse, contraction of blood vessels,
bronchodilator, fat combustionPseudoephedrin vasoconstriction on mucous membranes, rhinitis, Herbal extasy, doping
NHCH3
OH
(-)-Ephedrine
Ephedra alkaloidsO
NH2
(-)-Cathinone
L-Phe
O
O
Diketon
TA
NHCH3
OH
NHCH3
OH
NH2
OH
NH2
OH
N(CH3)2
OH
N(CH3)2
OH
(-)-Ephedrine(+)-Pseudoephedrine
(-)-Norephedrine (+)-Norpseudoephedrine (Cathine)
(-)-N-methylephedrine(+)-N-Methylpseudoephedrine
NH2
(+)-Amphetamine (Amfetamine)
Khat tea: Catha edulis (Celastraceae)Leaves: Flav., vol. oils, cathedulins, tannins, cathinone, cathine,….Young leaves: cathinone;↓hunger and fatigue, increased alertness,
general excitement, ↑self-confidence, talkativeness, “constant mild high”
AE: inflammation of oral mucosa, gastric disturbances, anorexia, hypertension, impotence
NH2
OH
(+)-Norpseudoephedrine (Cathine)
O
NH2
(-)-Cathinone
NH2
(+)-Amphetamine (Amfetamine)
NHCH3
OCH3
O
O
(MDMA) 3,4-methylene dioxyamphetamine = Ecstasy
Alkaloids 2
• Alkaloids originating from-Adrenaline, noradrenaline-Mescaline --Isoquinoline alkaloids---Benzylisoquinoline alkaloids: Opium alkaloids---Bis-benzyl-isoquinoline alkaloids:Tubocurarin---Terpenoid tetrahydro-isoquinoline alkaloids:
Ipecac alkaloids (Emetine, cephaeline)
CO2H
HO
NH2
Tyrosine
Alkaloids 2• Alkaloids originating fromAdrenaline
CO2H
HO
NH2
Tyrosine
CO2H
HO
NH2
CO2H
HO
NH2
HO
O2
HONH2
HO
HONH2
O2
HONHCH3
HO
OH
HONH2
HO
OH
Tyrosine Tyramine
L-DOPA Dopamine
Noradrenaline = Norepinephrine
Adrenaline= Epinephrine
Tyrosine hydroxylase +Tetrahydrobiopterin
Ascorbate
Mescalin and Lophophora williamsii (Cactaceae)
• Mescal buttons, South American Indians, religious rituals as hallucinogenic [unusual colored hallucinations, flashing lights, euphoria,disturbes normal mental functions. Psychotomimetic]
HONH2
HO
HONH2
MeO
MeONH2
MeO
OMeDopamine
Mescaline
Alkaloids 3Alkaloids originating from
Colchicine occurs in the seeds and corms; non-basic alkaloid;• Anti-inflammatory; acute attacks of gout; cytotoxic; anti-mitotic• Tox. Symptoms: swallowing difficulties, abdom. pain, ↓BP, muscle
cramp, resp. difficulties; Death: resp. arrest, CV collapse• Toxic dose: 10mg; above 40 mg death within 3 days; suicidal
attempts
CO2H
NH2
Phenylalanine
CO2H
HO
NH2
Tyrosine
C
B N
O
CH3
O
H3CO
H3CO
H3CO
H3CO
H
A
(-)-Colchicine
7-membered ring
Tropolone ring
1
35
7
10
128
Isoquinoline alkaloids and Benzylisoquinoline alkaloids
• Basic structures:
NH
Isoquinoline
12
345
6
7
8
NH
Tetrahydroisoquinoline
12
345
6
7 8
NH
Benzyltetrahydroisoquinolines
12
3
456
7 8
1'2'
3'
4' 5' 6'
N
Benzylisoquinolines
12
3
456
7 8
1'2'
3'
4' 5' 6'
Papaver somniferum (Papaveraceae)
• Opium: alkaloid richest drug• Alkaloids: 20-30%, meconic acid: ~5%; lactic acid: 1-2%;
other acids, enzyms, proteins, resins, fats• Morphine alkaloids: thebaine, codeine, morphine• Benzylisoquinoline alkaloids: Papaverine• Phthalidisoquinoline alkaloids: Noscapine (narcotine)• Several semisynthetic derivatives: Ethylmorphine,
diacetyl morphine (heroine), apomorphine, hydromorphone, hydrocodone, cotarnine,….
O
OH
HO2C CO2H
O
Meconic acid
Important opium alkaloids
Papaverine
• Thebaine Codeine Morphine
N
H3CO
H3CO
H3CO
H3COPapaverine
6
7
3'
4'
1
45
1'
8
Opium and morphine• Opium: CNS stimulant, analgesic, hypnotic, narcotic, stimulating /
depressing, checks excess peristalsis, pupil contraction; • Crude opium: ~10% morphine (analgesic, sleep inducer, cough treatment)• Powdered/granulated opium: • Laudandum (opium tincture): analgesic, narcotic• Camphorated opium (paregoric): antiperistaltic, diarrhea, dysentery; cough prep.• Dower’s powder (+ ipecac): diophoretic, influenza; sedative ;
• Morphine: mental detachment, tolerance, addiction, withdrawal symptoms• CNS: drowsiness, analgesia, euphoria Pupil: miosis Respiration: depressant; respiratory arrest GI: Stomach: HCl↓, small intestine: Biliary and pancreatic juices ↓
(delayed food digestion), large intestine: peristaltic waves↓, tone↑ (spasm, constipation)
Bronchi: large doses (bronchconstriction), Nausant and emetic effects, habit formation, …..
Codeine, thebaine, noscapine and papaverine• Codeine (methylmorphine): most widely used opium
alkaloid, antitussive and narcotic analgesic in the liver [-CH3]; (1/10 the potency of morphine); less toxic, less habit formation, little euphoria; constipation on long term use
• Thebaine: used primarily for the semi-synthetic production of other drugs, incl. codeine;
• Papaverine (not morphinane!): Smooth muscle relaxant, spasmolytic, little analgesic effect; male impotence!
• Noscapine (not morphinane!): Antitussive and cough suppressant, no analgesic or narcotic action; teratogenic!; antitumor action
• Papaveratum is a mixture of opium alkaloid: morhine (85.5%), codeine (7.8%), papaverine (6.7%); pain relief during surgery; may be combined with hyoscine
Semisynthetic and synthetic derivatives of morphine and thebaine
1-Morphine derivatives: codeine, pholcodine, ethylmorphine, hydromorphone, apomorphine, heroine, nalorphine; dextrometorphan, pentazocine, pethidine, fentanyl, methadone, tramadol
Morhine antagonist: naloxone
2-Thebaine derivatives: Codeine, etorphine, buprenorphine, oxymorphone :nalbuphine, naloxone, naltrexone
Bis-benzyl-isoquinoline alkaloids: Curare• Dried extract of barks and stems applied to various South American arrow
poisons1-Menispermaceae curare: Chondrodendron tomentosum : Bis-benzyl –THIQ
alkaloids; 4-7% alkaloids; d-tubocurarine2- Loganiaceae curare: Strychnos spp. : Indol alkaloids3-Mixture of both plants“Monkey test”; “head drop test” d-tubocurarine: H2O-sol., monoquaternary NH4-salt;
Paralysis, relaxation of voluntary muscles, competes with acetylcholine at nicotinic receptors; death: muscles of respiration stops to operate; treatment: artificial respiration and specific antidotes: anti-acetylcholine-esterase drugs: Physostigmine, neostigmineUses: Parkinson’s disease, MS, tetanus; skeletal muscle relaxant, surgery
Synth. Analogues: deca-, suxa-methonium; atracurium, vencuronium
Terpenoid tetrahydro-isoquinoline alkaloids Radix ipecacuanha
• Cephaelis ipecacuanha, C. acuminata (Fam. Rubiaceae)• Major alkaloids: emetine and cephaeline• Minor alkaloids: psychotrine and O-methyl-psychotrineIpecac: high doses: emetic; small doses: expectorantEmetine: antiaemebic, anti-protozoan, amebic dysentery,
expectorant, antiviral, antitumor; O-methylpsychotrine: AIDS (inhibition of HIV reverse transcriptase)
psychotrine O-methyl-psychotrine