Transcript Slide 1

Alkaloids 1
CO2H
NH2
• Alkaloids originating from
Phenylalanine
1-Capsaicinoides (Capsicum annuum [Solanaceae])
Capsaicine:pungent,
iritation on the skin,
rubafecient in
rheumatoid pain
O
H3CO
N
H
HO
Capsaicin
O
H3CO
N
H
HO
Hydroxycapsaicin
2-Ephedrine, pseudoephedrine (Ephedra sinica)
3-Cathine (Catha edulis)
OH
OH
Ephedrine
NHCH3
Ephedra sinica “ma huang”;
(-)-Ephedrine
Used in treatment of common cold,
↑BP and pulse, contraction of blood vessels,
bronchodilator, fat combustion
Pseudoephedrin
vasoconstriction on mucous membranes, rhinitis,
Herbal extasy, doping
Ephedra alkaloids
O
O
TA
L-Phe
O
NH2
Diketon
OH
OH
NH2
NH2
(-)-Norephedrine
OH
(-)-Cathinone
(+)-Norpseudoephedrine
(Cathine)
OH
NH2
NHCH3
(-)-Ephedrine
NHCH3
(+)-Pseudoephedrine
OH
N(CH3)2
(-)-N-methylephedrine
OH
N(CH3)2
(+)-N-Methylpseudoephedrine
(+)-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,
OH
O
anorexia, hypertension,
impotence
NH2
NH2
(+)-Norpseudoephedrine
(Cathine)
(-)-Cathinone
O
NH2
(+)-Amphetamine
(Amfetamine)
NHCH3
O
OCH3
(MDMA)
3,4-methylene
dioxyamphetamine
= Ecstasy
Alkaloids 2
CO2H
NH2
• Alkaloids originating from
HO Tyrosine
-Adrenaline, noradrenaline
-Mescaline
--Isoquinoline alkaloids
---Benzylisoquinoline alkaloids: Opium alkaloids
---Bis-benzyl-isoquinoline alkaloids:Tubocurarin
---Terpenoid tetrahydro-isoquinoline alkaloids:
Ipecac alkaloids (Emetine, cephaeline)
Alkaloids 2
• Alkaloids originating from
Adrenaline
CO2H
NH2
HO
Tyrosine
CO2H
NH2
HO
HO
Tyrosine
O2
NH2
Tyramine
OH
Tyrosine hydroxylase +
Tetrahydrobiopterin
HO
CO2H
HO
HO
Ascorbate
NH2
HO
L-DOPA
HO
NH2
HO
Dopamine
O2
NH2
Noradrenaline =
Norepinephrine
OH
HO
NHCH3
HO
Adrenaline= Epinephrine
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]
HO
NH2
HO
MeO
MeO
Dopamine
NH2
NH2
HO
MeO
OMe
Mescaline
Alkaloids 3
CO2H
CO2H
Alkaloids originating from
NH2
NH2
HO
Phenylalanine
Tyrosine
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
O
H3CO
CH3
5
3
A
B
7
N
1
H3CO
H3CO
H
12 C
10
H3CO
(-)-Colchicine
8
O
7-membered ring
Tropolone ring
Isoquinoline alkaloids and Benzylisoquinoline alkaloids
• Basic structures:
4
5
6
5
4
6
3
7
1
2
NH
8
Isoquinoline
5
6
7
1 NH
2
8
2'
3'
1'
4
5
4'
5'
6'
Benzyltetrahydroisoquinolines
6
7
4
3
8
7
3
2
1 NH
Tetrahydroisoquinoline
3
2'
3'
1 N
2
8
1'
4' 5' 6'
Benzylisoquinolines
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,
O
diacetyl morphine (heroine), apomorphine,
OH
hydromorphone, hydrocodone, cotarnine,….
HO2C
O
Meconic acid
CO2H
Important opium alkaloids
Papaverine
6
H3CO
7
N
1
8
H3CO
3'
H3CO
4
5
H3CO
1'
4'
Papaverine
• Thebaine
Codeine
Morphine
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
poisons
1-Menispermaceae curare: Chondrodendron tomentosum : Bis-benzyl –THIQ
alkaloids; 4-7% alkaloids; d-tubocurarine
2- Loganiaceae curare: Strychnos spp. : Indol alkaloids
3-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, neostigmine
Uses: 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-psychotrine
Ipecac: high doses: emetic; small doses: expectorant
Emetine: antiaemebic, anti-protozoan, amebic dysentery,
expectorant, antiviral, antitumor; O-methylpsychotrine: AIDS
(inhibition of HIV reverse transcriptase)
psychotrine
O-methyl-psychotrine