ALKALOID

GII THIU
Nhom ln nht, > 25000
hp cht a bit
Cha Nit, hu ht co tnh
base, v ng, dng rn (nicotine)
Nit thng tn ti trong
vng

- Thng c hot tnh rt mnh

- Ch xut hin trong thc vt
bc cao (him khi trong vi
khun), sinh tng hp t amino

acid

W. Meiner (1819)
(W. Meissner)

Hp cht hu c, ngun gc thc vt,

c cha N, c tnh kim.

Koenig

Hp cht hu c, ngun gc t nhin,

cha nhn pyridin, c tnh kim.

(1880)

Ladenburg (1900s)

Hp cht hu c,
c cha 1 Nit / d vng.

Winterstein & Tier

H.cht hu c c d vng Nit, c tnh kim,

(1910) c c tnh / TKTW. Ph.b hn ch / t nhin

Bentley

(1954)

Hp cht kim, ngun gc thc vt,

(vegetable alkali)
5

Tuy nhin, sau o a tim thy

Phyllobates aurotaenia
Dendrobates pumilio

Bufo bufo

Salamanders

?!!?

batrachotoxin
pumiliotoxin

serotonin
bufotenin,
bufotenidin

samanin
samandarin
6

Tetraodon miurus

Puffer Fish

Tetrodotoxin

Ascaris suum

Morphin

Claviceps purpurea

Claviceps sorghi

Agroclavin

Caffein

(1168 278 ng/g giun) # 1 ppm !

Su bi (Glomeris marginata)

Glomerin, homoglomerin

Hi ly (Castor fiber)

(P)-castoramin

S. William Pelletier (1983) :

Alkaloid la nhng hp cht hu c

co cha N.

co di vong.

phn b gii han trong sinh vt.

inh nghia nay bao gm cac alkaloid

co N trong h di vong (ai a s alkaloid)
co N ngoai h di vong (colchicin, capsaicin...)

co ngun gc thc vt ln ng vt

10

cht tng hp

cht truyn thng

Promethazin,
Alimemazin...
(tr cc ca alkaloid)
acid amin, histamin,
vitamin (B1, B2, B6 ...)

base ng vt

kiu nucleosid
(tr serotonin...)
11

MORPHINE ALKALOID KIU MU

Tnh base nh
eletron t do

Cha nitrogen

..

N CH3
heterocyclic ring

MeO

OH

Co trong thuc phin - Papaver somniferum

Thc vt cht trung tinh, cht acid

(mui, ng, cac cht chua . . .)

Thc vt cht co tinh kim

binh thng

bt thng

trai quy lut t nhin

13

Friedrich Wilhelm Adam Sertrner

(1783 - 1841) Dc s c
Morphine c c lp (1805) bi Adam Sertrner;
Nh dc s 22 tui t ting tm
14

1805, Sertrner . . .
NH A OPI (GY NG )

NH M CH T ACID

ACID MECONIC

Khng gy ng

Khng la hoat cht

NH M CH T KIM

1805

1806

MORPHINIUM

Thn Morpheus,
thn ca gic mng

Gy ng

HO T CH T

Papaver somniferum L

15

N CH3

MeO

Meconic acid

O
OH
Morphine

16

* N b tc Chinchon Peru (Nam M) b st rt

* Ngi da :
ly v ca mt
loi cy mc
sn ni Andes
em nu vi

nc ung.

Cinchona spp (Canh-ki-na)

B mang theo cy ny v Chu u v c nh vn vt hc

Thy in C. Lime t tn l cinchona, xut pht t tn b.

17

Plasmodium

JOSEPH PELLETIER &

BIENAYM CAVENTOU

Tch Quinine t Canh-ki-na

Nm 1820

18

1805

Morphin

Serturner

1817

Narcotin

Robiquet

1818

Strychnin, Brucin

Pelletier & Caventou

1819

Colchicin, Veratrin

Meissner & Caventou

1820

Quinin, Caffein

Runge; Pelletier & Caventou

1822

Emetin

Pelletier & Magendie

1827

Coniin

Giesecke; Geiger & Hess

1828

Nicotin

Posselt & Reimann

19

1831

Aconitin

Mein; Geiger & Hess

1832

Codein

Robiquet

1833

Atropin, Hyoscyamin

Geiger & Hess

1833

Thebain

Pelletier & Dumas

1842

Theobromin

Woskresenky

1848

Papaverin

Merck

1851

Cholin

Babo & Hirschbrunn

1855

Cocain

Gaedcke & Niemann (1860)

1870

Muscarin

Schmiedeberg & Koppe

1875

Ergotinin

C. Tanret . . .
20

1856, t Thng (Taxus baccata), H. Lucas p/lp Taxine.

1956, Graf chng minh : Taxine gm 3 alkaloid khc nhau
1967, t v thn Thng Taxus brevifolia (Taxaceae)
Taxol tinh khit = Paclitaxel (co tac dng chng ung th)
ch phm Taxol (Bristol-Myers Squibb)

Taxol cn c / Taxus cuspidata, T. wallichiana h Taxaceae

Nm 1969 :

1250 kg v thn 28 kg cao toan phn

10 g Taxol tinh khit

1971 : cu trc Taxol.

1988 : ban tng hp Taxol.

1994: Tng hp toan phn Taxol

21

Taxol (l IV, 30 mg / 5 ml)

Bristol-Myers-Squibb

22

Docetaxel Taxotere (Rhne-Poulenc-Rorer)

ban tng hp t 10-deacetyl baccatin III,

FDA chng nhn : 1996
23

Cong trnh nghien cu a phat minh hang tram chat alkaloid,

trch ly t cay co khac,

S phat minh ra alkaloid trong thc vat la tieng vang

rat ln trong nganh Hoa the ky XIX.
La nhng net noi bat manh trong s nghien cu
dc thao chong ung th, chong lao hoa va khang
khuan cua CATHARANTHUS va PACLITAXEL t na
sau the k XX.

24

Nguon goc alkaloid

Thong thng cac Alkaloid, trch t Dicotyledones (hai la mm),

Monocotyledones (mot la mam) , Cryptogames (hoa an), cac an hoa co
nhieu mach nh Lycopodiaceae (Ho Thach tung) cha rat nhieu
Alkaloid.

Moc vung nhiet i. S tieu hoa CO2 bi cay co la manh

nhat va yeu to nay ong vai tro quan trong trong sinh tong hp cac
alkaloid.
25% thc vat cha alkaloids
25

 Mot cay cha nhieu alkaloid rat t

dang t do ma luon trang thai hoa
hp vi acid hu c hoac vo c.
Cung mot cay alkaloid nay ong vai tro bien chat tnh
sinh ly oi vi alkaloid khac nh brucine giam oc tnh
cua Strychnine trong hot ma tien.
Ham lng alkaloid thay oi nhieu hay t tuy theo ieu kien
ben ngoai (kh hau, anh sang, mua thu hai), at ai (trang
thai vat ly va thanh phan hoa hoc), phan bon
26

Theo Polonopski, protein cua te bao thc vat cha amino acid nh
nhau.

Tai sao cay nay lai tao ra mot kieu alkaloid khac
cay kia? V vay vai tro alkaloid trong cay cha xac
nh c.

Chung la nhng chat d tr, chat thai hay on

vai tro la chat kch thch to?
27

VAI TR CA ALKALOIDS
Alkaloid trong thc vt
vai tr
c ch loi khc

Cht cm nhim
Allelochemical

T v

tn hiu

nicotin

28

Danh phap
Goi chung theo ten rieng.
Tiep v ng in xuat phat t:
1.Ten chi hoac ten cua loai cay + in, v du: Papaverin t papaver
somniferum; palmatin t Jatrorrhiza palmate; cocain t erythroxylum

coca.

- Strychnos

strychnin

- S. rotunda

rotundin

- Berberis

berberin

- R. serpentina serpentin

- Stemona

stemonin

- T. baccata

baccatin
29

2. Tac dung cua alkaloid + in

- gy nn

emetin

- gy khac nh vomicin
- febrifuga

febrifugin

- Curar

(tubo)curarin

- Morpheus morphin
- Atropos

atropin
Morpheus

Morphine

30

3. Ten ngi
- Pelletier pelletierin

- Nicot

nicotin

Tiep au ng
nor: mat mot nhom metyl
Ephedrin (C10H15ON) norephedrin (C9H13ON)
Apo: kh 1 nc
nor / epi / iso / neo / pseudo + X + in. (pseudoephedrin)
31

ATROPOS

ATROPIN

Clotho

Lachesis

spun the thread

measure the thread

N thn tng lai

N thn to s sng cut the thread of life

N thn coi s cht

32

1. theo tac dng dc ly

2. theo h / chi thc vt

alk / h Solanaceae / chi Atropa / chi Datura

3. theo ngun acid amin

: t tyr, tryp, orn, lys, his ...

4. theo ng sinh

: pseudo-, proto-, alk. thc

5. theo cu trc hoa hc

: tropan, quinolin, indol ...

6. theo sinh & cu trc hoa hc :

nhom ln : theo sinh tng hp

nhom nh : theo cu trc hoa hc

33

A. Alkaloid thc (N t acid amin thuc di vong).

- hu nh lun kim; cha 1N / di vong
- ai a s tn tai dang mui vi acid hu c
- co th dang t do (alk. base), dang N-oxid alkaloid
- mt s dang glycosid

- phn b hep, co hoat tinh sinh ly (thng c / CNS)

B. Protoalkaloid (N t acid amin khng cu thanh di vong).
(ephedrin, capsaicin, colchicin, hordenin, mescalin)
C. Pseudoalkaloid (N khng bt ngun t acid amin).
(cafein, coniin, aconitin, conessin, solanidin)

34

alkaloid thc (N/vong)

(N t acid amin)

proto-alkaloid (N/nhanh)

pseudo-alkaloid
(N khng t acid amin)

alk. pyrol, pyrolidin,

alk. tropan, indol, indolin

alk. quinolin, isoquinolin...

alk. pyridin, piperidin...

alk. phenyl alkylamin

alk. tropolon

alk. terpenoid, steroid

alk. purin, peptid

35

(true alkaloids)

La nhom ln & quan trng nht (alkaloid chinh thc)

Sinh nguyn : t cac acid amin (khac pseudo-alkaloid)

Co N / nhn di vong

c chia thanh nhiu nhom tuy nhn cn bn

(khac proto-alkaloid)

(pyrol, indol, tropan, quinolin, isoquinolin)

36

A.1. alkaloid pyrrol va pyrrolidin

O

O
N

Me

Me

Me

pyrrol

pyrrolidin

cuscohygrin

hygrin

An thn, gy ng

A.2. alkaloid pyrrolizidin: thng c vi gan

HO

CH2OH

pyrrolizidin

retronecin
37

A.3. alkaloid tropan: c tinh, ngn cn dn truyn t/h thn kinh

N

OH

tropanol (atropin)
COOH
N

tropan

Gin ng t,
tr co tht
N

OH

OOC

CH

Ph

CH2OH

hyoscyamin
An thn

COOMe

cocain

OH

scopanol (scopin)

ecgonin

OOC

Ph

(benzoyl)

Gim co tht rut, tr

au bng, lot t
trng

OOC

CH

Ph

CH2OH

scopolamin

38

3A.4. alkaloid pyridin va piperidin

Cau
COOMe

pyridin

Me

nicotin

Arecolin (tri giun)

iu hoa nhip tim
Lu
O

Me

Piperidin

Lobelin: an thn
tri ng c

Isopelletierin
Tri giun san 39

3A.5. alkaloid indol, indolin (1)

COOH

NH2

trytophan

gramin

indol

Me

HO

COOH

NH2

Serotonin
gim au, thuc ng

abrin

indolin

Me

NH

Me

Cam tho dy

kiu indol alkylamin

40

3A.5. alkaloid indol va indolin (2)

Me
Me

N
O

kiu eseran

Me

Me

Me

Eserin
Tri tng nhn ap

Me

kiu -carbolin

harmin
41

3A.5. alkaloid indol va indolin (3)

N

COOH
N

Me

kiu ergolin :
N

ergolin

acid lysergic

kiu strychnan :

N
O

MeO
N

MeO
O

strychnin

brucin

C trong ht m tin
Kch thch tiu ho
n ngon, d tiu

iu ho a/s mu
42

3A.5. alkaloid indol va indolin (4)

kiu yohimban
MeO

OMe

H
O

OOC
OMe OMe

Ba gc

OMe
OMe

Reserpin: ha huyt ap

MeO

N
H

O
OMe OH

yohimbin

O
OMe OMe

43
Ajmalicin:chng ung th

3A.6. alkaloid indolizidin

OH

OH

HO
N

indolizidin

HO

Castanospermin: tri tiu ng

Inh. glucosidase

3A.7. alkaloid quinolizidin

N
N

quinolizidin

Spartein: tri loan nhip tim

44

3A.8. alkaloid quinolein

acridin

quinolein

HO

HO

R
N

quinin (R = OMe)

quinidin (R = OMe)

cinchonin (R = H)

cinchonidin (R = H)
Cinchona sp.
45

3A.9. alkaloid iso-quinolein (1)

iso-quinolein

quinolein

kiu benzyl isoquinolein,

kiu aporphin,

kiu morphinan,

kiu protoberberin,

kiu protopin,

kiu emetin, . . .

46

3A.9. alkaloid iso-quinolein (2)

kiu benzyl isoquinolein

MeO
MeO

MeO
N

MeO

Me

OMe

OMe

OMe

OMe

Papaverin
Thuc phin; dn c

Laudanosin
Gy m ton thn

47

3A.9. alkaloid iso-quinolein (3)

kiu aporphin
MeO
N

MeO

Aporphin/
Parkinson

morphin

Me

nuciferin / Sen
HO

MeO

HO

Me

HO

kiu morphinan

Me

roemerin / Binh vi

Codein
N

Gim au-gy t

Me

48

3A.9. alkaloid iso-quinolein (4)

MeO

MeO

N
MeO
MeO

kiu protoberberin
MeO

O
O

palmatin

MeO

MeO

MeO

MeO

MeO

Berberin/nhimtrung
ng rut

Rotundin/an thn/gim au
Bnh vi

49

3A.9. alkaloid iso-quinolein (5)

kiu emetin
MeO
N

MeO

Et
CH2
H

OMe

OMe

Ngoai ra con cac kiu

- bisbenzyl iQ,
- protopin,

phtalid iQ,

benzophenanthridin . . .
50

3A.10. alkaloid quinazolin

O

OH
N

O
N

St rt

N
O

-dichroin

HO

-dichroin

(Thng sn, Dichroa febrifuga Saxifragaceae)

3A.11. alkaloid imidazol
Me

Et
N

imidazol

Pilocarpin/tng nhn ap
51

- c sinh phat nguyn t acid amin ( decarboxyl)

- cu trc n gin; gp / c thc vt ln ng vt
- thng l hp cht thm co N / mach nhanh
- mt s tac gi xp vao nhom amin thm ( alkaloid !)
- mt s tac gi 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 gin

(serotonin, gramin, abrin...)

52

COOH

NH2

HO

NH2

tyramin

COOH
NH2

HO

phenylalanin

tyrosin

O
MeO

Capsaicin/t
Cay/thng mu

HO

OH

MeO
NH2

MeO
OMe

Mescalin
o giac

HO

Me

Ephedrin
Vim xoang/mi

HO

Me

Me

Hordenin
Khng sinh 53

Nit co ngun t acid amin

COOH
N

NH2

N
N

Me

Me

MeO

tryptophan

MeO

MeO

gramin
OMe

HO

COOH

NH2

Serotonin
X hoa tim

NH

colchicin

Me

abrin
54

 alkaloid kiu purin : theobromin, cafein, theophyllin

O

O
Me
N

N
N

Me

N
N

Me

Me
O

Me

Me

O
N

N
N

Me

alkaloid kiu steroid : conessin, solanidin,

OH

N
N

conessin / Mc hoa trng

HO

solanidin / Solanaceae

55

 kiu alkaloid terpenoid : aconitin, mesaconin, taxol

Paclitaxel = Taxol

kiu alkaloid peptid : ergotamin, ergocryptinin

56

 s Nit :

- thng t 1 2 (i khi > 2 Nit dimer)

loai vong: - a s : di vong Nit

- mt s : vong carbon (protoalkaloid)

s vong:

- t khi 1 vong duy nht (protoalkaloid)

- thng 2 5 vng (strychnohexamin 15 vong)

bc Nit:

- thng la bc III (=N), bc II (NH)

thng co tinh kim; a s co pKa = 7 9.

57

 do m in c a Nit < Oxy

- lin kt N-H km phn cc hn lin kt O-H
- lin kt hydro N...H lng lo hn O...H
- alkaloid km phn cc hn alcol tng ng
im si c a alkaloid so vi alcol tng ng :
alcol > alk I > alk II > alk III > ether
tinh kim c a alkaloid so vi ammoniac :
NH4OH > alk IV > alk I > alk II > alk III (NR2)
pKa = 9,3 >

tinh kim yu nht dy

58

Hin nay, bit > 27.000 cu trc alcaloid / 6000 loai

thc vt (~20% thc vt bc cao).

Ch yu la thc vt bc cao, nganh hat kin.

It gp alk / nganh hat trn, nm & quyt thc vt.

Hu nh khng gp alk / TV bc thp (Ru, ia y, To)

Mt s ng vt, vi khun cng cha alkaloid.

59

(NAPRALERT, 2005) 27000

1975-2005 : 22.000 cht (02 alk / ngy)

(G.A. Cordell, 2001)

21200

(NAPRALERT, 1993)
16000

(Southon & Buckingham, 1989)

10000

1805-1975 : 5.000 cht (02 alk / thng)

4000
300

400

500

1000

1920

1930

1940

1950

5000

2000

1960

1970

1975

1990

1993

2001

60
2005

5.1. Cac h thc vt giau alcaloid

Apocynaceae

Papaveraceae

Fabaceae

Rutaceae

Liliaceae

Solanaceae

Amaryllidaceae

Menispermaceae

Rubiaceae

Loganiaceae

Asteraceae

Euphorbiaceae

Ranunculaceae

Berberidaceae

Cataceae

Cha tim thy alkaloid trong 4 b

Salicales, Fagales, Cucurbitales, Oleales
61

Mt s (~ 800) alkaloid t ng vt

Samandarin, samandaron t

Ky nhng la.

Batrachotoxin t ch c

(Phyllobates aurotaenia)

Bufotenin t tuyn da Coc

(Bufo bufo)

(P)-castoramin t Hi ly

(Castor fiber)

Tetrodotoxin t loai Ca coc

(Tetraodon spp.)

Morphin t Giun heo

(Ascaris suum, 2000) !!!

Glomerin t Su bi

(Glomeris marginata)

Muscopyridin t Hu xa

(Moschus moschiferus)
62

Mt s alkaloid t Nm (mushroom)

Alkaloid trong Nm c sinh tng hp t L-tryptophan.

T cac chi Psilocybe, Conocybe, Phanaeolus va Stoparia
serotonin, psilocin v psilocybin.
y la cac alkaloid co tac ng ln h TKTW
Hai loai nm cha psilosybin ang ch y :
- Psilocybe semilanceata
- Phanaeolus subbalteatus
63

Mt s alkaloid t ngnh Ru (moss)

T chi Lycopodium L. (Dng x)
annotinin, lycopodin v cernuin.
T loai Huperzia serrata va vai loai khac

huperzin A, J, K va L (co tac dng / Alzheimer).

phlegmariurin v cc c a phlegmariurin B.

64

Mt s alkaloid t vi khun v vi nm (fungus)

- T Claviceps purpurea

ergolin, ergotamin, agrolavin

- T Claviceps sorghi

caffein (2003)

- T Aspergillus terreus

asterrelenin, terretonin,

- T Aspergillus fumigatus

agrolavin

- T Penicillium janczewskii 2 alkaloid quinolinon.

- T Penicillium rivulum

communesin G, H

- T Penicillium citrinum

perinadin A v citrinadin A,

- T Pseudomonas spp.

tabtoxin v pyocyanin
65

5.2. Cac b phn cha alcaloid

Trong cy, alk. thng tp trung 1 s b phn nht inh

Hat

: M tin, Ca dc

Qu

: Anh tc, Tiu, t

La

: Tra, Thuc la

Hoa

: Ca dc

Thn : Ma hoang

: Ba gac, Lu

V thn : Canhkina

: Binh vi, Bach b

Hanh : N hoang cung

Hat thuc phin : khng co alkaloid.

66

5.3. S a dang va chuyn bit

Thng la 1 hn hp gm cac alcaloid cung nhom.

Thng co 1-2 alcaloid chinh (ham lng cao nht).
Cac cy cung h thng cha cac alc. cung nhom.
(Solanaceae alcaloid co nhn tropan)
Mt s h (Rubiaceae) cha nhiu nhom alcaloid
- cy Ca ph

: alc. nhn purin

- cy Canhkina : alc. nhn quinolin

- cy Ipeca

: alc. nhn isoquinolin

67

Tom lai
trong 1 h : co th gp nhiu nhom alcaloid.
cung 1 h : hy vng co cac alcaloid cung nhom.
cung 1 chi : rt hy vng co cac alcaloid cung nhom.
cung 1 alk. : co th gp nhiu h khac hn nhau.

Him khi alcaloid va tinh du ng thi hin din.

68

Berberin c trong 27 chi thuc >10 ho khc nhau :

1. Berberidaceae

6. Nandinaceae

2. Fumariaceae

7. Papaveraceae

3. Hydrastidaceae

8. Ranunculaceae

4. Juglandaceae

9. Rubiaceae,
Fabaceae

5. Menispermaceae

0. Rutaceae
69

Trong h Amaryllidaceae 30 chi co Lycorin

Amaryllis

Crinum

Haemanthus

Pancratium

Ammocharis

Curcoligo

Hippeastrum

Sprekelia

Brunsdonna

Cyrtanthus

Hymenocallis

Sternbergia

Buphane

Elisena

Leucojum

Ungernia

Calortemma

Eucharis

Lycoris

Urceolina

Chlidanthus

Eurycles

Narciscus

Valotta

Clivia

Estephia

Nerine

Zephyranthes

Cooperia

Galanthus
70

Caffein co trong nhiu cy

1. Tra

(Camellia sinensis L., Theaceae)

2. C ph

(Coffea spp., Rubiaceae)

3. Mate

(Ilex paraguariensis,
Ilex vomitoria, Aquifoliaceae)

4. Guarana

(Paullinia cupana, Sapindaceae)

5. Cola

(Cola acuminata, Sterculiaceae)

6. Citrus

(Citrus spp., Rutaceae; bao phn)

71

5.4. Ham lng alcaloid :

Thay i theo iu kin dinh dng, sinh ly c a cy.
noi chung, [alkaloid] thng thp (# )
it alcaloid

: di 1% (Wagner, 1996)

nhiu alcaloid : 1% (berberin: 2-3% / Vang ng)

Vai trng hp c bit

- v thn Canhkina cha

6 10% alcaloid

- nha Thuc phin cha 20 30% alcaloid

72

5.5. Dang alcaloid trong cy

dang base

dang mui

dang glycosid

(# 0)

(a s)

(it)

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
73

6.1. Ly tinh
a s [C,H,O,N] rn / tO thng

(tr arecolin; pilocarpidin)

a s [C,H,

N] lng /

(tr sempervirin, conessin)

kt tinh c
mp ro rang
(nu bn tO)

tO

thng

bay hi c,
bn nhit,
ct ko c

74

Trong t nhin, cac alkaloid thng co. . .

- 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 t trin
- pKa : thng t 7 9 (nn kim hoa v pH = pKa + 2)
75

Ni chung, cc alkaloid base :

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 bn si-gel pha thun (Si-OH).
khc phc : thm kim vao pha ng, vt s gn.
3. km bn (nht la khi + tO)

nn chit di dang alkaloid mui (bn hn)

76

 alcaloid base :

thng km tan / nc
d tan / dmhc km phcc
(tr cafein, nicotin, coniin, colchicin, spartein tan / nc)

alcaloid mui :

d tan / nc
km tan / dmhc km ph.cc ( EP)
(tr berberin clorid, berberin nitrat km tan / nc
reserpin.HCl lai tan / CHCl3)

alcaloid phenol : dang base vn tan c / d.dich kim

(morphin, cephaelin)
77

Strychnin
- kh tan trong ether
- d tan trong CHCl3.
- rt d tan / hn hp Et2O - CHCl3 (1 : 1)
Mt s alcaloid (ephedrin, cafein)

co th thng hoa c ap sut thng

dung pp thng hoa tinh ch
(trn bt tra vi vi, un / cat),

78

6.2.

Hoa tinh

COOH
N

6.2.1. Tinh kim

kim mnh

nicotin

kim yu

A S

alcaloid + acid

Me

COOH
N

(*)

kim rt yu khng kim

(**)

acid yu

cafein

colchicin

arecaidin*

codein

ricinin

guvacin**

piperin

theobromin

isoguvacin

mui tng ng

alcaloid + mui kim loai nng mui phc

alcaloid + thuc th chung t a hay mau
79

 Alkaloid base co tinh kim yu hn cac kim v c.

[alk mui] s gii phong ra [alk base]
bi Na2CO3, amoniac, M(OH)n
[alk.H]+.X + OH

[alk] + (X/H2O)

Nu alcaloid co 2 Nit (2 chc base) :

- c 2 N u co tinh kim : co th tao 2 loai mui.

Vi d : Quinin

Q.HCl v Q.2HCl

- 1 N c tinh base qua yu : ch co th tao 1 loai mui.

Vi d : Strychnin (Str)2SO4

80

alcaloid (pKa)

alcaloid (pKa)

alcaloid (pKa)

berberin 2.5

pilocarpin 7.0

caffein 3.6

vinblastin 7.4

ammoniac 9.3

acid acetic 4.8

heroin 7.6

-ephedrin 9.4

reserpin 6.6

scopolamin 7.7

ephedrin 9.6

quinin, brucin 7.8

amphetamin 9.9

quinidin, codein 7.9

strychnin 8.3

morphin 9.2 & 7.9

atropin 10.2
nicotin 11.0 & 6.2

cocain 8.6
81

 pH = pKa + 3 > 99.9% dang alk. base

pH = pKa 3

> 99.9% dang alk. mui

nu SKLM 1 alkaloid pH # pKa thi :

# 50% mu dang alk. base (km phn cc; Rf cao)
# 50% mu dang alk. mui (phn cc hn; Rf thp)

vt bi ko dai, co th tach thanh 2 nhom vt

cn thm kim n pH = pKa + (2 3)

82

SKLM alkaloid / Si-gel NP

vi pha ng co pH << [pKa 2]

alk.base, km phn cc hn, bi ko vt.

alk.mui, phn cc hn, vt gn hn.

Ngoai phn cc c a pha ng,

cn ch y n pH khi SKLM alkaloid !
83

pH c a mt s dung dich alkaloid

pH 3

papaverin HCl

5
5

codein phosphat

5.5

eserin sulfat

eserin salicylat

pH 7

6
4
6.5

ephedrin HCl
caffein base

quinin sulfat
quinin HCl

5.5
84

6.2.2. Phn ng tao t a (Y/N)

ta v nh hinh

ta tinh th

Valse-Mayer

Dragendorff

- AuCl3

Bouchardat

acid tannic

- PtCl3

Bertrand (silico-tungstic)

- acid picric (Hager)

- acid picrolinic

Reineckat

Scheibler

- acid styphnic

(ac. phospho-tungstic)

Sonnenschein (ac. phospho-molybdic)

- thth Marme
(CdI2-KI)

thth Bouchardat = thth Wagner (Iod / KI)

85

thuc th

thnh phn

to ta v nh hinh mu

Bouchardat

KI + I2

nu, nu

ValseMayer

KI + HgI2

bng trng vng ng

Dragendorff KI + BiI3

cam

Marm

KI + CdI2

trng vng (c th k tinh)

Bertrand

acid silicotungstic trng trng ng

Tannin

acid tannic

trng (tan / cn, AcOH, NH3)

86

thuc th

thnh phn

ta v nh hinh mu

Reineckat

hng, tan / aceton 50%

ammoni tetrasulfocyanid (nh lng o mu)
diamin chromat III
c th kt tinh dng kh
c trng, mp r (nh danh)

Scheibler

acid phospho-tungstic

trng

Sonnenchein

acid phospho-molybdic

trng

Cobalt
thiocyanat

Co(SCN)2

xanh
87

 nhay thay i tuy loai thuc th, tuy loai alkaloid

Thuc th km bn / kim (ddich th: tr.tinh acid nhe)
T a co th tan lai trong

- thuc th tha, trong MeOH, EtOH : Marm

- thuc th tha, trong MeOH, EtOH, AcOH : Mayer

- MeOH, EtOH, AcOH, NH4OH : acid tannic

T a co thanh phn n inh
( inh lng bng ph.phap cn gian tip) : Bertrand
88

Johann Georg Nol Dragendorff (18361898)

89

Mt hp cht khng-alkaloid s (+) vi thuc th Dragendorff

khi tai nhom chc Oxy va carbon- (ni vi oxy) co mt cao.
Vi vy, cac aldehyd, ceton, ether, epoxid, peroxid, ester, lacton
- nu tai carbon- co ni i / co cac nhom alkyl t do
- thi s phn ng (+) vi th th Dragendorff.
min la s mt tai nguyn t Oxy va tai carbon- nay

khng bi gim i (do hiu ng rt in t hoc do ni cu hydro)

90

alkaloid

quinin
morphin
caffein

Valse-Mayer

Bouchardat

Dragendorff

100 ppm

1700 ppm

8 ppm
400 ppm

91

Alkaloid

Dragendorff

Zaffaroni *

Morphin

50 g

10 g

Apomorphin

20 g

10 g

Papaverin, Thebain

10 g

10 g

Codein, Heroin, Dionin

10 g

Narcotin
Narcein (km nhy)

50 g

20 g
50 g

*(thuc th Zaffaroni = Kali Iodo-Platinat)

92

thuc th
Vng clorid

thnh phn
AuCl3. HCl

Platin clorid

PtCl4. 2HCl

acid picric

2,4,6-trinitrophenol

acid styphnic

2,4,6-trinitroresorcin

acid picrolonic

ca p-nitrobenzen

to ta kt tinh
c mu thay i

ty loi alkaloid

c mu vng cam
c hinh dng c trng
c im chy xc nh

93

NO 2
NO 2

OH
NO 2

acid picric

NO 2
NO 2

OH
HO

NO 2
NO 2

N
N

Me

NO 2

acid styphnic

acid picrolonic

+ alkaloid
- mu vng cam

tinh th co

- hinh dang c trng

- im chy xac inh

inh danh
alkaloid
94

7.2.3. Phn ng vi thuc th c hiu (inh danh)

thng kt hp vi SKLM // alcaloid chun

thuc th

thnh phn

Alkaloid

Erdmann acid sulfo-nitric

Conessin

Frohde

acid sulfo-molybdic Morphin

s cho mu

vng xanh lc
tm

Mandelin acid sulfo-vanadic

Strychnin

tm xanh

Merke

Codein

xanh ngoc

acid sulfo-selenic

Marquis

sulfo-formol

Morphin

tm

Wasicky

sulfo-PDAB

Indol

xanh tm n

Brucin

mu

HNO3

acid nitric .

95

 Tac nhn: cac cht co tinh oxy-hoa manh

(acid sulfuric ., acid nitric ., sulfochromic...)
Mi trng thc hin : thng la khan.
Cho sn phm mau kha chuyn bit, gip inh danh alk.
Mau thng km bn (quan sat nhanh)
Mau thay i tuy cac iu kin phn ng
(tO, pH va nht la mc tinh khit c a mu alkaloid).
96

7.1. Nguyn tc chung

Alk la cac base yu, trong cy co th dang

- alk. mui vi acid hu c, v c (d chuyn dang)

- alk. phc hp bn vi tannin

(kho chuyn dang)

Nu mun chit ngay di dang alk. mui :

Chit trc tip [Alc.H]+.X vi dung mi thich hp
Nu mun chit di dang alk. base :
cn dung kim (tr.binh / manh) tao phn ng :
[alk.H]+.X + OH

[alk] + (X/H2O)

97

Alk. mui / dc liu

ROH

/ H+

Dmhc

Alk. mui / ROH

Dmhc

/ kim

Alk. base / dmhc

/ kim

HOH

Alk. base / dmhc

/ H+

Alk. mui / H2O

Thay i pH va dung mi

98

7.2.

Cac phng phap chit xut alkaloid

7.2.1. Chit dang alcaloid base

- xay bt dc liu (khng qua min)
- lam m va vi kim thich hp (manh, yu)
- chit bng dmi hc km ph.cc (DCM, Cf, Bz)
- thu hi dung mi; tinh ch (loai tap); kt tinh
Khi lam m, tranh dc liu t qua
tranh un nong (c ) dich alkaloid base (khng bn).
thich hp khi thao tac nhanh (inh tinh, inh lng).
khng s dng cho chit xut (ngm kit lu / kim).

99

7.2.2. Chit dang alcaloid base bay hi

- xay bt dc liu (khng qua min)
- lam m va vi kim thich hp
- chit bng phng phap sc hi nc
- thng dung cho inh tinh, inh lng ngay.

100

nhit k va
b tip nc

hi nc si

dc liu + kim

Alk base
ngng t

dung dich
acid long
101

7.2.3. Chit cac alcaloid base thng hoa

- xay bt dc liu
- lam m va vi kim thich hp
- un nong bng nhit kh (cach cat)
- thu tinh th alc. base va thng hoa
- tinh ch, kt tinh
Vi d : Chit Cafein t bt Tra cam, tra vn.

102

7.2.4. Chit dang alcaloid mui

- xay bt dc liu (khng qua min)

- lam m va vi dung mi chit, nap vao binh

- chit bng dung mi (cn / cn acid / nc acid)
- c thu hi bt cn.
- tinh ch (loai tap + chuyn dang); kt tinh
Phng phap nay co th ap dng cho sn xut
vi quy m trung binh ln.

103

PHNG PHP STAS-OTTO (1850)

- Alkaloid mui : tan / ROH, khng tan / Et2O.

- Alkaloid base : tan / Et2O. (tr morphin base).

1. Chit ly alkaloid mui bng ROH / acid.

2. Ra dich [ROH / acid] vi Et2O loai tap km phn cc.

3. Trung hoa dich [ROH / acid] vi soda (natri carbonat).

4. Lc ly phn tan trong Et2O; c Et2O, thu alkaloid base.

104

PP. STAS OTTO (1850)

Alk. mui / dc liu

Chit = cn acid

ban u :

Alk. mui / dich acid

cn - acid tartric

Lc vi Et2O

tap bng nc
dmhc l Et2O, CHCl3
hin nay :

Lc d.mi hu c

Alk. base / dmhc

acid thay i
dmhc thay i

B tap tan / Et2O

Alk. mui / dich acid

+ Kim,

loai tap = dmhc /

C thu hi cn

H+

C thu hi

d.mi hu c

Cn Alkaloid base

105

8.1. Loai b tap mau bng than hoat tinh

cn thm do t l C* it mt alkaloid.
8.2. Chuyn dang alk mui alk base

chn loai kim NH4OH, Na2CO3, NaOH, Ca(OH)2

chn pH thich hp (pH = pKa +2)
chn dmhc Bz, Et2O, DCM, Cf, Cf Et2O (3 : 1)
8.3. Chuyn dang alk base alk mui
chn loai acid (sulfuric, HCl, AcOH, tartric)

chn pH thich hp (pH = pKa 2)

chn dung mi (EtOH, MeOH, HOH)

106

Lu y khi tinh ch

- alk. base bc IV (berberin)

- alk. phenolat (morphin)

tan c trong nc

- nicotin base, cafein base

cach phn lp chuyn bit
i vi hn hp {alk kim yu + alk kim manh}: co th
- kim hoa ln 1 vi NH3, lc vi dmhc (thu alk kim yu)
- kim hoa ln 2 vi NaOH, lc dmhc (thu alk kim manh)
107

Phng phap SKLM ch hoa (p-TLC)

vung khng phun thuc th

vung phun
thuc th

vung phun
thuc th
(A)

(B)

(C)

cao (A), (B), (C) (vung khng c th.th) ly alcaloid

108

Phng phap sc ky ct (SKC)

a. SKC hp ph
cht hph : Si-gel (15-40 hay 40-63 m)
co th nhi Si-gel vi d.dich m kim
mu nap

: alcaloid base (it tap); k ~ 30 60

khai trin

: hay dung CHCl3 MeOH (x : y)

sao cho Rf ~ 0,30 / SKLM 1 ln

theo doi

: SKLM / UV 254 nm hay / Dragendorff

thu phn oan tinh khit, kt tinh alcaloid base.

109

Phng phap SKC

b. SKC ry phn t
Thng s dng pha tinh la Sephadex LH-20
Mu th : alk. base toan phn con ln tap / (Cf MeOH)
Khai trin vi MeOH, MeOH CHCl3
- cac hp cht co MW ln s ra trc
- cac hp cht co MW nh s ra sau.
110

Phng phap SKC

c. SKC phn b o
Thng dung pha tinh Diaion HP-20 (Mitsubishi).
Mu : alk. mui toan phn con it tap / (MeOH H2O)
Khai trin ct vi (H2O MeOH) (100 : 0 0 : 100)
- cac hp cht phn cc manh hn : ra trc
- cac hp cht phn cc yu hn : ra sau

111

9.1. Trn vi phu (phn ng hoa m)

vi
phu

ra bng
cn tartric

ri + thuc th
Bouchardat

Kt lun

c ta nu

c protein / alcaloid.
(th tip vi phu 2 v 3)

c ra

vn c ta nu

c protein; alk ???

c ra

khng cn ta nu

c alcaloid.

khng ra

- alcaloid va protein u cho t a vi th th Bouchardat

- alc. tan / cn tartric; protein khng tan / cn tartric.

112

9.2. Bng phng phap sc ky

Mc ich
- co alkaloid ???
- co dc liu A, B, C ???
- co alkaloid x, y, z ???

- ham lng x, y, z ???

Cac k thut thng dng
- SKLM (TLC; HP-TLC; p-TLC)
- HPLC (LC-UV; LC-PDA; LC-MS )
113

9.2.1. Trn SKLM

Bn mng : Si-gel F254, RP-18 (Merck )
mu chm : alk base (it tap) / CHCl3 (chm vach)
dung mi

: thng thm kim (hu c, v c) yu *

phat hin

: UV 254 nm / Dragendorff / th th khac

* Thm kim n pH (pKa + 2)

lam gn vt alkaloid (tranh ko vt)
* K thut thm kim

- tm vao giy bo hoa binh sc ky

- tm vao pha tinh; thm ngay vao h d.mi

114

H dung mi (2 3 thanh phn)

phn cc kem

phn cc tr.binh

phn cc mnh

EP, n-6, n-7

EtOAc

n-BuOH

Tol, Bz, Et2O

Me2CO

i-PrOH

Cf, DCM

AcCN

EtOH, MeOH

Nguyn tc chung: Dung mi // Mu th (alkaloid)

Dung mi thng thm kim yu (pH modifiers)
- NH4OH ( %), dimethyl formamid (DMF)

- diethylamin, triethylamin (DEA, TEA)

115

Mu th
- thng la alkaloid base (toan phn, phn oan)

- mu c hoa trong Bz, Cf, DCM.

- nn chm thanh vach (1 mm 5-10 mm)
- mu cao hn mc dung mi ~ 5 mm

- khai trin 1 ln, n ln; chiu khai trin:

Phat hin vt
- soi UV 254 (tt quang) / 365 nm (phat quang)
- h hi Iod (cc alk. co / cu trc)

- phun / nhng thuc th Dragendorff **

- phun / nhng thuc th c hiu (it s dng).

116

9.3. Bng phn ng hoa hc

Lu y : khi lam cac ph.ng tao t a / mau
nn thc hin vi cac d.dich alk. mui
nh gi

Quan st thy dung dch

()

vn trong

(+)

c l, khng lng

(++)

c nhiu, ta xut hin sau vi pht

(+++)

ta r, lng nhanh; thm 1 giot TT ta tip

(++++)

ta nhiu, lng ngay; thm 1 giot TT ta tip

117

9.3. Bng phn ng hoa hc

Bt Dc liu

a. NH4OH c

H2SO4 2%

b. CHCl3
Alk base / CHCl3

Alk mui / nc acid

a. Lc vi H2SO4 2%

a. NH4OH n pH 10-11

b. Ly lp nc acid

b. Lc vi CHCl3

Alk mui / nc acid

a. Th2 chung
b. Th2 c hiu

Alk base / CHCl3

SKLM
CHCl3

cn Alkaloid base

Th2 c 118
hiu

Mt s phn ng mau c hiu thng dng

alcaloid

phn ng mu

Tropan

Vitali-Morin

alcaloid

phn ng mu

Berberin

Oxyberberin

Sulfo-chromic

Quinin

Thaleoquinin

Brucin

Cacothelin

Quinin

Erythroquinin

Cafein

Murexid

Quinin

Huynh quang

Strychnin

119

Nguyn tc chung

alk. mui / dc liu

alk. mui / d.mi

thay i pH

alk. base / d.mi

tap
cn alk. base sach

1. p.phap cn

3. o quang

2. acid base

4. pp. sc ky

tap

120

10.1. Phng phap cn : p dng khi

- khng .lng = acid-base c (alk. kim qua yu)
- alkaloid cha ro v cu trc hoa hc
- hn hp phc tap c a nhiu alkaloid

P b (kho cn)

- mun anh gia s b v alkaloid

Mc tin cy
- km chinh xac (alk% qua it; tap tha)
- khc phc = phng phap cn gian tip
P ln (d cn)
121

10.1. Phng phap cn

chit dang alk. acid hoc base
cafein, nicotin

loai tap (cht bo, tannin )

i pH nhiu ln (chuyn dang)

Bertrand
Bertrand.(alk)4

alkaloid base
Palkaloid

cn trc tip, gian tip

(cn gian tip) 122

10.2. Ph.phap th tich

alk. base
acid tha
(HCl, H2SO4 long)

kim

vi cac ch thi mau vng pH acid :

- methyl (4.2 6.3 vang)
- methyl cam (3.0 4.4 vang)

(co th + methylen xanh)

123

10.2. Ph.phap th tich (m.trng khan)

- nn: AcOH bng
- acid percloric tha
- ch thi mau: Tim tinh th
- ap dng: k c alk. kim qua yu (cafein, colchicin)

- chinh xac > ph.phap cn

tim tinh th : vang lc (acid) xanh lc (tr.tinh) tim (kim)

124

10.3. Phng phap o mau

- mau t nhin (berberin, palmatin)
- mau do + th th tao mau (Dragendorff, oxy-hoa)
- mau huynh quang (quinin sulfat)
Thc hin
- o trc tip t dung dich mau

hay quy v 1 alkaloid ai din

- o do qut vt mau (scanner / SKLM)
thng lam // alkaloid chun
125

10.4. Phng phap SKLM

SKLM
tao mau

o vt

din tich vt
cng mau

[alkaloid %]

cao vt
scanner

10.5. Phng phap HPLC

Thng kt hp vi nhiu cach ch.bi mu (SPE, SPME)
vi nhiu detector khac nhau (UV, IR, RI, MS, ELSD...)

126

 La nhng cht chuyn hoa th cp, cht bai tit hoc la

sn phm cui trong qua trinh chuyn hoa c a thc vt.

La nhng cht d tr Nit, tham gia vao chu trinh Nit
trong thc vt.
i khi la nhng cht tich ly dn t thc n (Kin ly
alk. t la cy; ch, Coc n kin ch, Coc co alk.)
La nhng cht bo v, chng cac sinh vt n thc vt.
La v khi hoa hc trong t v, cn trong qua trinh
sinh tn nht la ng vt (Ca, Coc, Ky nhng ...)

127

Alkaloid thng co hoat tinh sinh hc manh n rt manh

kha nhiu cht c s dng trong y hc.

mt s cht dung lam cht c dung trong sn bn

(tubocurarin / Curar)
mt s cht qua c, khng dung trong y hc
(Gelsemin trong L ngn).
nhiu cht co thm tac ng nguy hai n x hi

(gy nghin, ma ty, o giac)

If Nature had any sense, She wouldnt make alkaloids !

(John Comforth) 128

Khi thc vt co nhom alkaloid, thi tac dng c a dc liu

thng do nhom alk. (trong o thng do 1 alk. ch yu).
Trn h thn kinh
- kch thch TKTW

: cafein, strychnin

- c ch TKTW

: morphin, codein

- kich thich trc giao cm : ephedrin

- lit trc giao cm

: yohimbin

- kich thich pho giao cm : pilocarpin

- lit pho giao cm

: atropin
129

 Trn cac c quan khac

- Gy t

: cocain

- Gim au

: morphin

- Gim ho

: Codein

- Gim co tht : Papaverin

- Tri st rt

: Quinin

- Dit giun san : Arecolin

- Dit khun : Berberin, Emetin - Ha huyt ap : Reserpin

- Tri ung th : Taxol, Vincristin, Vinblastin, Vincamin

130

Hypnos (God of sleep; father of Morpheus, God of dreams)

and his brother, Thanatos (God of death).

Thanatos
Hypnos

131

Peyote = Lophophora williamsii, h Cactaceae

Lophophora williamsii,
Trichocereus spp.

Mescalin
132

Alkaloid t ng vt
Alkaloid cng co trong ng vt, nht la B nhiu chn, Coc, ch, Ca,
Ky nhng va ng vt co v (Saxidomus, Salamandra, Phyllobates,
Dendrobates, Castor, Moschus, Solenopsis, Glomeris, Odontomachus v
Polyzonium).
Trong hi sinh vt, c bit t cac loai Hi min (Ptilocaulis spiculifer,
Hemimycale spp., Crambe crambe, Monanchora arbuscula, M. ungiculata)
tach c cac alkaloid guanidin (batzelladin J, ptilomycaulin A,
ptilocaulin v isoptilocaulin)
Sao bin (Fromia monilis va Celerina heffernani) cng co alkaloid.
133

Alkaloid cng co da 1 s loai lng c. Co 3 b lng c :

B Anura

vi > 4500 loai Coc, ch,

B Urodela

vi > 450 loai ky nhng, thn ln,

B Apoda

vi > 160 loi su khng chn.

T da Anura species, Osteocephalus taurinus, O. oophagus va O.

langsdorfii bufetenin co tinh gy o giac kiu LSD.
T da coc Melanophryniscus montevidensis nhm pumiliotoxin (PTX)
v alkaloid nhm indolizidin.

134

The lady bird (Coccinellidae) v Ong cng cha alkaloid.

Mt s loai bm m Utethesia ornatix thu alkaloid pyrrolizidin khi cn
la u trung sng gc cac loai Crotalaria (Fabaceae).
Longitarsus lateripunctatus, 1 loi ong do n la cy Pulmonaria abscura,
cng cha alkaloid pyrrolizidin.
Cc loi kin Anochetum grandidieri va Tetramorium electrum, cha
alkaloid pyrrolizidin, c tim thy trong da day ch Mantella.
ch Dendrobates pumilio cha alkaloid dendrobatid la do n cac ng
vt chn t tich ly cac alkaloid nay.
Vi alkaloid pyrroloindol (pseudo-phrynaminol) c tim thy loai ch
Pseudophryne coriacea.
135

Hin co hn 800 alkaloid co TDSH c tim thy t da cac loai lng c

Tr trng hp 2 nhm samandarin v pseudophrynamin,

dng nh tt c cac alkaloid con lai u co ngun t thc phm.

ong

batrachotoxin v coccinelline-like tricyclics

kin, mi

pumiliotoxin.

kin

decahydroquinolin, izidin, pyrrolidin v piperidin.

kin

histrionicotoxin, lehmizidin and tricyclic gephyrotoxin

136

T Bryozoan (Flustra foliacea) nhiu brom-alkaloid nhom indol nh

flustramin, deformylflustramin, deformylfrustrabromin A, B.

T sa D n la cy Erythrinia poeppigiana erythrinan alkaloid

(-erythroidin v dihydro--erythroidin) co tac dng kiu curare.
Cac nhom alkaloid ng vt bao gm t nhom isoquinolin, -carbolin,
n thiazolidin, arising from vitamin B6, chloral and glyoxylic acid.
T lu, ngi ta vn cho rng cac alkaloid tetrahydro-isoquinolin
vn co ngun gc t thc vt.
Tuy nhin, cng co tac gi coi chng la cac alkaloid ni sinh t nhin
t c th ngi va ng vt.
137

6. Phn loi:
Pyridine
Pyrolidine pyridine
Quinoline
Isoquinoline
Phenantrene
Indol.

138

6.1 Nhom pyridine:

Sn c ban
4
5

N
1

139

Nhom pyridine: Trigoneline (C7H7O2N) trong hat Ca

phe
COO
Ba(OH)2

CH3NH2

N
Cl

CH3
HCl, P
COOH
CH3Cl
N
140

Acid nicotinic ( acid piridin_3_carboxilic)

Tong hp trigoniline (PP HANTZSCH)

AgOH

MeI
N

COOH

COOMe

COOH
KOH, T

N I
Me

COO

( H2O)
N

OH

Me

N
Me
Trigonelin

141

Ricinine (C8H8O2N2) trong hat Thau dau

OMe
CN
N

Me
142

Nhng alkaloid co trong ht Cau ( Areca cotechu )

nh sau:
COOH
N
H

Guvacine (acid1,2,5,6_tetrahidronicotinic)
143

COOCH3
N
H
Guvacoline (1,2,5,6_tetrahidronicotinatmetil)

144

COOCH3
N
CH3

Arecoline (N_metil_1,2,5,6_tetrahidronicotinatmetil)
145

Nhng alkaloid co trong cay lu (Punica granatum) h

Punicaece

N
HO

Peletierine
146

CH2

CH3

Isopeletierine
147

Nhng alkaloid co trong hat tieu en (piper nigrum)

ho Piperaceae
N
O

O
O

Piperine
148

Piper nigrum L.

149

Nhm Pyridine:

N
1

Ricinine (C8H8O2N2)

Trigoneline (C7H7O2N)
Guvacine, Guvacoline, Arecoline
Peletierine, Isopeletierine
Piperine
150

6.2 Nhom Pirolidine_Pyridine.

Alkaloid co trong cay thuoc la (nicotiana tabacum) ho Solanaceae

151

N
N

CH3

Nicotine
COOH
COOH
N
Acid nicotinic
( Pyridine_3_carboxilic)

N
Acid picolic
( Pyridine_2_carboxilic)

COOH

N
Acid isonicotine
(Pryridine_4_carboxilic)

152

N
N

Nicotyrine

CH3

H
Nor _ Nicotine

Nicotine la chat kch thch cua he oi giao cam, dang tiem cho ong vat, gay s
kch thch he thong than kinh trung ng.
S hap thu khoi thuoc la gay ra not so benh: Ve tieu hoa, tuan hoan, than
kinh.
Hut thuoc la a den cac hien tng ngo oc: Kch ng ng phoi, nhieu
loan ve tim, ve tuan hoan , ve tieu hoa, ve than kinh.
S ot chay ieu thuoc cang cham, ngoai nicotine, con cac chat oc khac:
HCN, CO2, CO. 100g thuoc la cha 2% nicotine.
153

6.3 Nhng alkaloid thuoc nhom quinoline

Alkaloid cua vo cay quinquina (cinchona Rubiaceae): Co hai

alkaloid quan trong : quinine va cinchonine..

2
8

N
1
154

155

Cinchona succirubra P.
(Cy canhkina)

156

H3CO

6'

C
4'

8
3'

HO
5'

10

CH

11

CH2

2'

7'
8'

N
1'

157

158

159

C3 nhom etilen
C6 nhom metoxi
C9nhom
hidroxi
9
C cau cua quinine cha 4 carbon phi oi xng:
C3,C4,C8,C9.
(3etilen-9-hidroxi-6metoxiruban)
160

161

6'

C
4'

8
3'

HO
5'

10

N
1

2'

7'
8'

N
1'

Cinchonine

CH

11
7

CH2

5
9

2
6'

5'

7'
8'

8
4'

N
1'

3
2

3'
2'

Ruban
162

Cinchonine

163

164

165

C cau lap the cua quinine, quinidine Cinchonine,

cinchonidine.
H2C CH

H2C CH

HO

H
Q

HO

C9

H
Q' '

Vi

Q=

Q' '

H3CO

Vi

N1

H
6

CH

C9

HO

7
8

N1

H 2C

Q=

N
166

6.4 Alkaloid thuoc nhom isoquinoline:

7
8

167

Papaver somniferum L.
(Cy thuc phin )

168

169

Alkaloid c trch t cay a phien co nhan isoquinoline:

Papaverine, laudanosine, laudanine

H3CO

H3CO

H3CO

H3CO

CH2
6'
5'

1'

CH3

H3CO

CH2
1'

CH2
2'
3'

4'

OCH3

OCH3

6'
5'

1'

6'
2'
3'

4'

OCH3

CH3

H3CO

5'

2'
3'

4'

OH

OCH3

OCH3

170

Papaverine ( C20H21O4N )

171

Laudanosine

172

6.5 Nhng alkaloid thuoc nhom phenantren:

morphine la alkaloid quan trong nhat trong cay A phien.

2

HO

1
11

4
12

HO

13

H
H

10

14

6 15

CH3

16
8

(C17H19O3N)

173

Morphine

174

H3CO

H3CO

O
N

H
H

CH3

CH3

OCH3

OH

Codein (C18H21O3N)

The bain (C19H21O3N)

C* : C5, C6, C9, C13, C14

OH : C3, C6
Nhom epoxi: C4 C5
Vong 6 cha N-CH3: C13 C9
Noi oi : C7, C8

175

Codeine

176

6.6 Alkaloid thuoc nhom Indol:

1
7

2
3
4

H
177

Alkaloid cua chi Strychnos ho Loganiaceae: Strychnine, Brucine, Vomicine.

17

R1

16

1
6

I
R2

IV

15 N

19

VI

III

VII

12

20
21

13 14

9
10

II
5

18

22

23

11

R1, R2 = H : Strychnine
R1, R2 = OCH3 : Brucine

178

Trychnine

179

Trychnos ( h Loganiaceae)

180

Strychnos nux-vomica L.
(Cy ma tin)

181

Alkaloid cua chi Rauwolfia, ho Apocynaceae: Ajmaline, Ajmalicine, Serpentine,

Reserpine, Yohimbine.
6

9
8

10

13

H3CO

11
12

OCH3

H
H3COOC

O
OCH3

C
O

Reserpine (C33H40O9N2)

OCH3
OCH3

182

Reserpine

183

184

Rauwolfia serpentina

185

Yohimbine ( C21H26O3N2)
6

9
8

10

13
11
12

N
1

H
H

H3COOC
OH
186

Yohimbine

C*: C3, C15, C16, C17, C20.

Nhom amino nh cap
amino tam cap
OH tai C17
carbometoxi tai C16

187

188

Yohimbine

189

7. Phng phap ly trch:

7.1. Alkaloid de bay hi:

S dung phng phap loi cuon hi nc. Base hien dien

trong cay trang thai muoi, cay c phi kho va
nghien nat thanh bot, tron bot cay vi chat kiem vo
c amoniac hoac voi ) thu c alkaloid dang muoi base t
do va sau o c loi cuon bi hi nc

V du: nicotine ( trong cay thuoc la )

190

7.2 Alkaloid on nh :
S o tong quat ly trch alkaloid on nh

191

8. Thuoc th e nhan biet alkaloid:

8.1 Thuoc th tao tua ( thuoc th chung):

Thuoc th nay cho vi alkaloid nhng muoi n gian

hoac dang phc, chung co the ton tai dang ket tinh
hoac vo nh hnh, t tan hoac khong tan trong nc, phan
ng thc hien trong moi trng acid nghia la cho thuoc
th tac dung vi muoi alkaloid trong nc

192

Thuoc th iodur

Thuoc th Bouchardat:
Iod 2,5g
KI
5g
Nc cat 100ml
Cho tram hien mau nau, tan trong lng tha thuoc
th, no lam tram hien hoan toan dung dch acid cua
alkaloid

193

Thuoc th Mayer_ Valser

* Thuoc th Mayer
HgCl2 6,8g
KI
25g
Nc cat
1000ml
* Thuoc th Valser
HgI2
Lng tha
KI
10g
Nc cat
100ml
e yen va loc
194

Iodur Bismuth va K
Thuoc th Dragendorff
Bi(NO3)3 trung hoa
HNO3 am ac
KI
Nc cat

30g

20g

68

250ml

Hoa tan Bi(NO3)3 trong HNO3. Loc them dung dch KI (68g) trong
60ml nc cat . e yen 24gi. Loc. Pha loang thanh 250ml vi
nc cat .
195

Thuoc th lam tram hien dung dch H2SO4 cua alkaloid,

tram hien mau o, tan trong lng tha thuoc th.

Thuoc th Yvon
Nitrat Bi
KI
HCl am ac
Nc cat

1,5g

7g
20 giot
20ml
196

8.2 Thuoc th tao mau (thuoc th rieng ):

o la thuoc th cho vi moi alkaloid hoac mot nhom

alkaloid co cau truc gan giong nhau co mot mau ac
trng.

IRDMAN (H2SO4+HNO3)=a.sulfonitric.
MARQUIS = sulfoformol
Morphine cho mau o tm.
197

 LAFON= sulfoselenieu
Codein cho mau xanh cam thach.

Thuoc th HNO3:
Brucine cho mau o mau; Ajmaline cho mau o.thuoc
th co the la tac nhan
kh nh H2SO4
Oxi hoa nh H2O=,k2Cr2O7, HNO3, H2SO4.
Oxi hoa kh.
oi khi ngi ta dung ca tac nhan trung hp hoa.

198

199

200

Colchicum autumnale L.

Cay ca la xe (Solanum laciniatum)

Chuc cac SV at ket qua tot vi chng

alkaloid.

4. Tnh cht
Alkaloid

la chat co trong lng phan t kha ln.

Cha oxigene thng la chat ran, ket tinh, khong

loi cuon bi hi nc.

Alkaloid thng khong mau, v ang va co tnh

trien quang .