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AI CNG
BM. DC LIU
TRNG AI HOC Y DC CN TH
Nguyn Ngoc Quynh
MC TIU HC TP
1. inh nghia, danh phap, cac tinh cht ly hoa,
trang thai t nhin cua alcaloid trong dc
liu.
2. Phn loai alkaloid theo cu truc hoa hoc.
3. Ph.phap chit xut, phn lp akc. t dc
liu.
4. Cac ph.phap thng dung inh tinh, inh
lng akc.
5. Cac ni dung chinh v 20* dc liu cha
alcaloid.
NI DUNG
1. Lich s, inh nghia, Danh phap
2. Cu truc Phn loai
3. Phn b trong t nhin
4. Tinh cht chung
5. Chit xut Phn lp
6. Kim nghim (inh tinh inh lng)
7. Cng dung
1.Lich s, inh nghia, Danh phap
Nm 1806
AUX PHARMACIENS
ALKALOD
Phyllobates aurotaenia
Dendrobates pumilio Bufo bufo Salamanders
?!!?
Tetrodotoxin
Ascaris suum Claviceps purpurea Claviceps sorghi
Promethazin, Alimemazin...
cht tng hp
(tr cac cua alkaloid)
Morphine
O O
N N N N N
H H Me Me
Me
pyrrolizidin retronecin
Phn loi alkaloid
1. Alkaloid thc
1.3. alkaloid tropan
N OH N O N OH
N OH N OOC CH Ph
CH2OH
ecgonin hyoscyamin
COOMe
N OOC Ph
O N OOC CH Ph
CH2OH
cocain
(benzoyl) scopolamin
Phn loi alkaloid
1. Alkaloid thc
1.4. alkaloid pyridin va piperidin
COOMe
N
N
N N Me
O O O
N N N
H Me H
COOH Me
N
NH2 Me
N N N
H H H
HO COOH
NH2 NH
N N N Me
H H H
Me Me
N
Me
O
N N N N
H H Me Me
N
N
N H Me
N
H
harmin
kiu -carbolin
Phn loi alkaloid
1. Alkaloid thc
1.5. alkaloid indol va indolin (3)
COOH
N H N Me
N N
H H
N N
MeO
N MeO N
O O O O
O OOC OMe
reserpin
N N
N MeO N
H H
O O O
yohimbin ajmalicin
Phn loi alkaloid
1. Alkaloid thc
1.6. alkaloid indolizidin
OH OH
HO
N N
HO
indolizidin castanospermin
N
N
quinolizidin spartein
Phn loi alkaloid
1. Alkaloid thc
1.8. alkaloid quinolein
N N
quinolein acridin
HO HO
N N
R R
N N
N N
quinolein iso-quinolein
MeO MeO
N N Me
MeO MeO
OMe OMe
OMe OMe
papaverin laudanosin
Phn loi alkaloid
1. Alkaloid thc
1.9. alkaloid iso-quinolein (3)
kiu aporphin
MeO O
N R N Me N Me
MeO O
HO MeO
morphin O O
codein
N Me N Me
HO HO
kiu morphinan
Phn loi alkaloid
1. Alkaloid thc
1.9. alkaloid iso-quinolein (4)
MeO
N N
MeO
MeO
MeO
O MeO
N N
O MeO
MeO MeO
MeO MeO
berberin rotundin
(tetrahydro palmatin)
Phn loi alkaloid
1. Alkaloid thc
1.9. alkaloid iso-quinolein (5)
kiu emetin
MeO
N
MeO
Et
CH2
OMe
H N
OMe
- protopin, benzophenanthridin . . .
Phn loi alkaloid
1. Alkaloid thc
1.10. alkaloid quinazolin
O O
OH
N N
N N
O O
N N HO
-dichroin -dichroin
(Thng sn, Dichroa febrifuga Saxifragaceae)
1.11. alkaloid imidazol
Me Et
N N
N N O O
H H
imidazol pilocarpin
2. Cu truc Phn loai
Phn loi alkaloid
2. Proto-alkaloid
C sinh phat nguyn t acid amin ( decarboxyl)
Cu truc n gian; gp / ca thc vt ln ng vt
Thng l hp cht thm co N / mach nhanh
Mt s tac gia xp vao nhom amin thm ( alkaloid !)
Mt s tac gia lai coi cac amin thng la 1 dang
alkaloid.
Cac kiu proto-alkaloid thng gp
- kiu phenyl alkylamin (ephedrin, mescalin, capsaicin...)
- kiu tropolon (colchicin...)
- kiu indol n gian (serotonin, gramin, abrin...)
COOH COOH
O
MeO
N
H
capsaicin
HO
OH
MeO
NH2
MeO N N
HO H Me HO Me Me
OMe
COOH Me MeO
N
O
NH2 Me
N N MeO
N
H H
MeO H
tryptophan gramin
O
OMe
HO COOH
NH
colchicin
NH2
N N Me
H H
serotonin abrin
2. Cu truc Phn loai
Phn loi alkaloid
3. Pseudo-alkaloid
alkaloid kiu purin : theobromin, cafein, theophyllin
O O O
Me Me Me Me
N N N N N N
O N N O N N O N N
Me Me Me
N HO
Paclitaxel = Taxol
(NAPRALERT, 1993)
16000
5000
4000
2000
500 1000
300 400
1920 1930 1940 1950 1960 1970 1975 1990 1993 2001 2005
3.Phn b trong t nhin
Cac ho thc vt giau alkaloid
Apocynaceae Papaveraceae Fabaceae
Rutaceae Liliaceae Solanaceae
Amaryllidaceae MenispermaceaeRubiaceae
Loganiaceae Asteraceae Euphorbiaceae
Ranunculaceae Berberidaceae Cataceae
Cha tim thy alkaloid trong 4 b
Salicales, Fagales, Cucurbitales, Oleales
3.Phn b trong t nhin
Mt s (~ 800) alkaloid t ng vt
Mt s alkaloid t Nm (mushroom)
Mt s alkaloid t ngnh Ru (moss)
Mt s alkaloid t vi khun v vi nm
(fungus)
T Claviceps sorghi caffein (2003)
3.Phn b trong t nhin
S a dang va chuyn bit
Tom lai
1. Berberidaceae 6. Nandinaceae
2. Fumariaceae 7. Papaveraceae
3. Hydrastidaceae 8. Ranunculaceae
5. Menispermaceae 0. Rutaceae
Trong ho Amaryllidaceae 30 chi co Lycorin
Cooperia Galanthus
Caffein co trong nhiu cy
vi acid v c (it)
vi acid hu c thng thng
vi acid hu c c bit
- acid meconic, tropic, aconitic
- acid gallic, tannic; tannin
4.Tinh cht chung
4.1. Ly tinh
kt tinh c
a s [C,H,O,N] rn / tO thng
mp ro rang
(tr arecolin; pilocarpidin)
(nu bn tO)
bay hi c,
a s [C,H, N] lng / tO thng
bn nhit,
(tr sempervirin, conessin)
ct ko c
4.Tinh cht chung
4.1. Ly tinh
- mui : thng khng mui
- vi : thng ng
(piperin, capsaicin cay; aconitin khng ng !!!)
- mau : thng khng mau
(berberin, palmatin, chelidonin: mau vang
jatrorrhizin mau cam, pyocyanin mau xanh)
- []D : thng ta trin
- pKa : thng t 7 9 (nn kim hoa v pH = pKa + 2)
4.Tinh cht chung
4.1. Ly tinh
1. co phn cc trung binh
- alk. base tan / dmhc co ph.cc trung binh n yu;
- nhng kho tan / cac dmhc qua km ph.cc nh EP, n6.
- p dng chit & tinh ch (kim hoa, bin alk. mui
alk. base, chit alk. base bng Bz, DCM, Cf, Et2O...)
2. co tinh kim
d bi ko vt trn ban si-gel pha thun (Si-OH).
khc phc : thm kim vao pha ng, vt s gon.
3. km bn (nht la khi + tO)
nn chit di dang alkaloid mui (bn hn)
4.Tinh cht chung
4.1. Ly tinh
alcaloid base : thng km tan / nc
d tan / dmhc km phcc
(tr cafein, nicotin, coniin, colchicin, spartein tan / nc)
colchicin
cafein arecaidin*
ricinin
nicotin A S codein guvacin**
ricinin
piperin isoguvacin
theobromin
50% pH
~25%
~10%
[base l.hp]
[alk. mui]+ + H2O pH = pKa + log
[acid]
Ka
[alk. base]
[alk. base] + H3O+ pH = pKa + log
[alk. mui]
Valse-Mayer - AuCl3
Bouchardat - PtCl3
Bertrand (silico-tungstic) - acid picric (Hager)
- acid picrolinic
Reineckat - acid styphnic
Scheibler (ac. phospho-tungstic) - thth Marme
Sonnenschein (ac. phospho- (CdI2-KI)
molybdic)
thuc th thanh phn tao tua v inh hinh mau
Bouchardat KI + I2 nu, nu
Valse-
KI + HgI2 bng trng vng ng
Mayer
quinin 8 ppm
vi
ra bng ri + thuc th
ph Kt lun
cn tartric Bouchardat
u
1 khng ra co tua nu
2 co ra vn co tua nu
Cho san phm mau kha chuyn bit, giup inh danh alk.
Thay i pH va dung mi
5. Chit xut Phn lp
5.1. CC PHNG PHP CHIT XUT ALKALOID
5.1.1. Chit dang alkaloid base
Bt dc liu
Lm m dc liu
Bt dc liu
Kim hoa
Chit bng dung mi km
phn cc
Dung mi cha
alkaloid Base
5. Chit xut Phn lp
5.1.2. Chit dang alcaloid base bay hi
nhit k va
b tip nc
hi nc si Alk base
ngng t
dc liu + kim
dung dich
acid loang
5. Chit xut Phn lp
5.1.3. Chit cac alcaloid base thng hoa
bong / khan lanh
phien knh
tinh the
Alkaloid chen nung
bot dc lieu
li amiant
R
5. Chit xut Phn lp
5.1. Chit dang alkaloid mui
Bt dc liu
Lm m dc liu
Bt dc liu
lam m
Chit bng dung mi cn,
cn acid, nc acid
Dung mi cha
alkaloid mui
PP. STAS OTTO (1850) Alk. mui / dc liu
hin nay :
Alk. base / dmhc
acid thay i
C thu hi d.mi hu c
loai tap = dmhc / H+
dmhc thay i Cn Alkaloid base
5. Chit xut Phn lp
5.2. PHN LP V TINH CH
a. SKC hp ph
b. SKC ry phn t
R H+
alcaloid
BH+ Cl H+ Cl (pH acid)
mui
R BH+
NH4+ OH HOH
R NH4+
B
alcaloid
base
c.2. vi ct Anionit
R OH
BH+ HOH
alcaloid
mui
Cl R Cl
B alcaloid
base
d. SKC phn b ao
vi
ra bng ri + thuc th
ph Kt lun
cn tartric Bouchardat
u
1 khng ra co tua nu
2 co ra vn co tua nu
a. NH4OH c H2SO4 2%
b. CHCl3
tap tap
cn alk. base sach
1. p.phap cn 3. o quang
2. acid base 4. pp. sc ky
6. Kim nghim dc liu
6.2. nh lng
6.2.1.Phng phap cn
alkaloid base
P b (kho cn)
cafein, nicotin
Bertrand
Bertrand.(alk)4
P ln (d cn) Palkaloid
alk. base
acid tha
(HCl, H2SO4 loang)
kim
Afghanist
Trung (1350 tn) 1265 tn
an
(vng Ch thp vng)
Pakistan 85 tn
Myanmar 2365 tn
ng Nam (2645 tn) Lo 210 tn
(vng Tam gic vng) Vit Nam 45 tn
Thi Lan 25 tn
Columbia 66 tn
Nam M (112 tn)
Mexico 46 tn
trn 4000 tn
Din tich trng Thuc phin (1990-2005, ngn ha)
250 ngn ha
250
R
L 200
200
150
150
M
100
50
A
- 2005: 104.000 ha
200
160 165.8
154.1 155.1
150
108.7
100 89.5
81.4
62.2
44.2
50 32.8
0
1990 1993 1997 2001 2003 2005
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
San lng nha Opium ca Afghanistan
(1990-2006; ngan tn)
8000
6724
6000
5032
4630
3765 3611 3748
4000
3091
2568 2574
2183
2000
204
0
1994 2004
1990
1 2 3 4 5 6 7 8 10 11 2001
9 1999 12 13 14 15 16 2006
17
O
N Me
R2O
% trong
R1 R2
nha
morphin
H H 8 17%
*
codein* Me H 0,7 5%
thebain* Me Me 0,1 2.5%
-morphin, neopin rt thp
b. Nhm benzyl isoquinolin
MeO MeO
N N Me
MeO MeO
OMe OR1
OMe OR2
papaverin* R1 R2
(0.5 1.5%) laudanin H Me
laudanidin Me H
lausanosin Me Me
c. Nhm phtalid isoquinolin
O O
N Me N Me
O O O O
OMe OH
OMe OMe
OMe OMe
HO
O
Me
N HO
O
O Me
N
O
protopin apomorphin
(gy nn, RLC, Parkinson)
MeO
Me
N
MeO
O
O
ngoi ra cn vi nhm alkaloid
O
khac, ham lng rt thp.
cryptonin
Thanh phn khac
- khong 56%, ng, cht nhy, pectin (20%).
- protein, acid amin t do.
HOOC O COOH
- cac acid hu c:
acid lactic, fumaric, acetic, vanilic,
O
mau
Anh tuc xac (qua a ly nha) : con rt it alkaloid.
L : t alkaloid (0,020,04%).
ta morphin base th
NH4OH n pH 8-9
HCl
tinh th morphin HCl ta morphin base TK
Chit xut
2. Phng phap Kabay morphin
- Chit bt qua bng nc nong, c thanh cao c.
- Chit cao c bng cn nong, c thu hi cn.
- ri + (NH4)2SO4 v NH4OH + benzen
- Loc thu ring dich benzen va ta morphin base th.
benzen codein, thebain, narcotin (HCl).
ta morphin base morphin.HCl.
5. Phan ng Huseman
- alkaloid base + H2SO4 / BM mau cam.
- ngui + NaNO2 (hay HNO3 ) xanh tm
mau mt mau (morphin apomorphin).
- nhay: 10 mg morphin.
inh tinh (3)
6. inh tinh bng SKLM
- Cht hp ph: silica gel
- Dung mi khai trin:
benzen MeOH (4 : 1),
xylen-MEK-MeOH-DEA (40:60:6:2).
- Phat hin: thuc th Dragendorff.
inh lng (1)
inh lng morphin trong nha thuc phin
Nguyn tc: mophin (va alkaloid co OH phenol)
tan it / nc, tan c / dung dich kim.
Tinh kt qua: nhn vi 1 h s bu tr