ALKALOID

GI I THI U
Nhm l n nh t, > 25000 h p ch t bi t Ch a Nit , h u h t c tnh base, v nicotine) Nit th vng ng t n t i trong ng, d ng r n (-

- Th

ng c ho t tnh r t m nh

- Ch xu t hi n trong th c v t b c cao (hi m khi trong vi khu n), sinh t ng h p t amino acid

W. Mei ner (1819) (W. Meissner) Koenig (1880)

H p ch t h u c , ngu n g c th c v t, c ch a N, c tnh ki m. H p ch t h u c , ngu n g c t nhin, ch a nhn pyridin, c tnh ki m. H p ch t h u c , c ch a 1 Nit / d vng. H.ch t h u c c d vng Nit , c tnh ki m, c tnh / TKTW. Ph.b h n ch / t nhin

Ladenburg (1900s) Winterstein & Tier

(1910) c Bentley (1954)

H p ch t ki m, ngu n g c th c v t, (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

Claviceps purpurea

Claviceps sorghi

Morphin

Agroclavin

Caffein

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

Su bi (Glomeris marginata)

H i ly (Castor fiber)

Glomerin, homoglomerin

(P)-castoramin

S. William Pelletier (1983) : Alkaloid la nh ng h p cht h u c co ch a N. co di vong. phn b gi i 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 th c vt l n ng vt
10

ch t t ng h p

Promethazin, Alimemazin... (tr cc c a alkaloid) acid amin, histamin, vitamin (B1, B2, B6 ...) ki u nucleosid (tr serotonin...)
11

ch t truy n th ng

base

ng v t

MORPHINE ALKALOID KI U M U
Tnh base nh eletron t do Ch a nitrogen

N CH3
heterocyclic ring

..

MeO

OH

C trong thu c phi n - Papaver somniferum

Th c vt p cht trung tinh, cht acid (mui, ng, cac cht chua . . .)

binh th

ng

Th c vt p cht co tinh kim

bt th

ng

trai quy lut t nhin

13

Friedrich Wilhelm Adam Sertrner (1783 - 1841) D c s c Morphine c c l p (1805) b i Adam Sertrner; Nh d c s 22 tu i t ti ng t m

14

1805, Sertrner . . .

1805

1806

Th n Morpheus,
th n c a gi c m ng

Papaver somniferum L

15

N CH3

MeO

Meconic acid

O OH Morphine

16

*N

b t

c Chinchon

Peru (Nam M ) b s t rt * Ng i da :

l yv c am t loi cy m c s n n ni Andes em n u v i c u ng.

Cinchona spp (Canh-ki-na)

B mang theo cy ny v Chu u v Th y i n C. Lime c nh v n v t h c tn b.
17

t tn l cinchona, xu t pht t

Plasmodium

JOSEPH PELLETIER & BIENAYM CAVENTOU

Tch Quinine t Canh-ki-na N m 1820

18

1805 1817 1818 1819 1820 1822 1827 1828

Morphin Narcotin Strychnin, Brucin Colchicin, Veratrin Quinin, Caffein Emetin Coniin Nicotin

Serturner Robiquet Pelletier & Caventou Meissner & Caventou Runge; Pelletier & Caventou Pelletier & Magendie Giesecke; Geiger & Hess Posselt & Reimann

19

1831 1832 1833 1833 1842 1848 1851 1855 1870 1875

Aconitin Codein Atropin, Hyoscyamin Thebain Theobromin Papaverin Cholin Cocain Muscarin Ergotinin

Mein; Geiger & Hess Robiquet Geiger & Hess Pelletier & Dumas Woskresenky Merck Babo & Hirschbrunn Gaedcke & Niemann (1860) Schmiedeberg & Koppe C. Tanret . . .
20

1856, t Thng

(Taxus baccata), H. Lucas p/l p Taxine. 3 alkaloid khc nhau

1956, Graf ch ng minh : Taxine g m 1967, t v thn Thng

Taxus brevifolia (Taxaceae)

p Taxol tinh khi t = Paclitaxel (c tc d ng ch ng ung th ) p ch ph m Taxol (Bristol-Myers Squibb) Taxol cn c / Taxus cuspidata, T. wallichiana h Taxaceae N m 1969 : 1250 kg v thn p 28 kg cao ton ph n p 10 g Taxol tinh khi t 1971 : c u trc Taxol. 1988 : bn t ng h p Taxol. 1994: T ng h p ton ph n Taxol
21

Taxol (l IV, 30 mg / 5 ml) Bristol-Myers-Squibb

22

Docetaxel p Taxotere (Rhne-Poulenc-Rorer) bn t ng h p t 10-deacetyl baccatin III, FDA ch ng nh n : 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 m m), 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 26 hoa hoc), phan bon

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 ong vai tro la chat kch thch to?

27

VAI TR C A ALKALOIDS
Alkaloid trong th c v t
vai tr
c ch o loi khc

Ch t c m nhi m Allelochemical

T v

tn hi u

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 - Berberis - Stemona p strychnin p berberin p stemonin - S. rotunda - T. baccata p rotundin p baccatin
29

- R. serpentina p serpentin

2. Tac dung cua - gy nn p emetin - Curar alkaloid + in

- gy kh c nh p vomicin - febrifuga p febrifugin - Atropos

p (tubo)curarin p atropin Morpheus Morphine

- Morpheus p morphin

30

3. Ten ngi - Pelletier p pelletierin - Nicot p nicotin

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

31

ATROPOS

ATROPIN

Clotho

Lachesis

spun the thread

N th n t o s s ng cut the thread of life N th n coi s ch t

measure the thread N th n t ng lai

32

1. theo tac dung d

c ly

2. theo ho / chi th c vt alk / ho Solanaceae / chi Atropa / chi Datura 3. theo ngu n acid amin 4. theo ng sinh : t tyr, tryp, orn, lys, his ... : pseudo-, proto-, alk. th c : tropan, quinolin, indol ...

5. theo cu truc hoa hoc 6. theo sinh

& cu truc hoa hoc :

nhom l n : theo sinh t ng h p nhom nho : theo cu truc hoa hoc

33

A. Alkaloid th c (N t acid amin p thu c d vng). - hu nh lun kim; ch a i as t nt i - c th -m ts 1N / di vong dang mui v i acid h u c

d ng t do (alk. base), d ng N-oxid alkaloid d ng glycosid ng c / CNS)

- phn b hep, co hoat tinh sinh ly (th

B. Protoalkaloid (N t acid amin khng c u thnh d vng). (ephedrin, capsaicin, colchicin, hordenin, mescalin ) C. Pseudoalkaloid (N khng b t ngu n t acid amin). (cafein, coniin, aconitin, conessin, solanidin )
34

alk. pyrol, pyrolidin, alkaloid th c (N/vong) (N t acid amin) proto-alkaloid (N/nhanh) alk. tropan, indol, indolin alk. quinolin, isoquinolin... alk. pyridin, piperidin... alk. phenyl alkylamin alk. tropolon alk. terpenoid, steroid alk. purin, peptid
35

pseudo-alkaloid (N khng t acid amin)

(true alkaloids) La nhom l n & quan trong nht (alkaloid chinh th c) Sinh nguyn : t cac acid amin alkaloid) Co N / nhn di vong (khac proto-alkaloid) (khac pseudo-

c chia thanh nhiu nhom tuy nhn c n ban (pyrol, indol, tropan, quinolin, isoquinolin )

36

A.1. alkaloid pyrrol va pyrrolidin

O
N H
N H

O N Me N Me

N Me

pyrrol

pyrrolidin

hygrin ng

cuscohygrin
An th n, gy ng

A.2. alkaloid pyrrolizidin: th

HO N

c v i gan
CH2OH N

pyrrolizidin

retronecin
37

A.3. alkaloid tropan:

N OH

c tnh, ng n c n d n truy n t/h th n kinh

N

OH

tropanol (atropin)
COOH N OH

tropan

scopanol (scopin)

Gin ng t , tr co th t
N OOC CH Ph CH2OH

ecgonin
COOMe N OOC Ph

hyoscyamin
An th n
O N OOC CH Ph

cocain

(benzoyl)

Gi m co th t ru t, tr au b ng, lot t trng

CH2OH

scopolamin

38

3A.4. alkaloid pyridin va piperidin Cau

COOMe

N Me

pyridin

nicotin

Arecolin (tr giun) i u ha nh p tim

L u
O
O N H

N H

N Me

Piperidin

Lobelin: an th n tr ng c

Isopelletierin Tr giun sn 39

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

COOH
N N H Me Me

N H

N H

NH2

indol
HO

trytophan
NH2

gramin
COOH NH

N H

Me

N H

indolin

Serotonin gi m au, thu c ng

abrin
Cam th o dy

kiu indol alkylamin

40

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

Me
Me N O N Me Me

N H

N H

N Me

kiu eseran

Eserin Tr t ng nhn p

N H

N H Me

kiu F-carbolin

harmin
41

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

N H

COOH N Me

kiu ergolin :
N H N H

ergolin kiu strychnan :

N O O

acid lysergic

MeO MeO O N O

strychnin
Kch thch tiu ho n ngon, d tiu

brucin
i u ho a/s mu
42

C trong h t m ti n

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

MeO N H O OOC OMe OMe N OMe OMe OMe

Ba g c

Reserpin: h huy t p

N H O

MeO

N H O

O OMe OMe

OMe OH

yohimbin

43 Ajmalicin:ch ng ung th

3A.6. alkaloid indolizidin

OH HO N HO N OH

indolizidin 3A.7. alkaloid quinolizidin

Castanospermin: tr ti u ng Inh. glucosidase

N

quinolizidin

Spartein: tr lo n nh p tim
44

3A.8. alkaloid quinolein

quinolein
F
HO R N N

acridin
E
HO R N N

quinin (R = OMe) cinchonin (R = H) Cinchona sp.

quinidin (R = OMe) cinchonidin (R = H)

45

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

quinolein

iso-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 N OMe OMe

MeO MeO N Me OMe OMe

Papaverin Thu c phi n; dn c

Laudanosin Gy m ton thn

47

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

MeO N R MeO N Me O O N Me

Aporphin/ Parkinson
HO

nuciferin / Sen
MeO

roemerin / Binh vi

morphin

O N Me

O N

Codein
Me

Gi m au-gy t
48

HO

HO

kiu morphinan

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

MeO

MeO

N MeO MeO

kiu protoberberin
O O N MeO MeO
MeO MeO

palmatin

N MeO MeO

Berberin/nhi mtrng ng ru t

Rotundin/an th n/gi m au
Bnh vi
49

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

MeO MeO N Et CH2 H N OMe OMe

Ngoai ra con cac kiu - bisbenzyl iQ, - protopin, phtalid iQ,

50

benzophenanthridin . . .

3A.10. alkaloid quinazolin

O N N O OH O N N N O HO N

S t rt

E-dichroin (Th

-dichroin

ng s n, Dichroa febrifuga Saxifragaceae)

3A.11. alkaloid imidazol

N N H
Me N N H O O Et

imidazol

Pilocarpin/t ng nhn p

51

- c sinh phat nguyn t acid amin ( - cu truc - th

decarboxyl)

n gian; g p / ca th c vt ln ng vt

ng l h p cht th m co N / mach nhanh alkaloid !)

- mt s tac gia xp vao nhom amin th m (

- mt s tac gia lai coi cac amin th ng la 1 dang alkaloid. cac kiu proto-alkaloid th - kiu tropolon - kiu indol n gian ng g p

- kiu phenyl alkylamin (ephedrin, mescalin, capsaicin...) (colchicin...) (serotonin, gramin, abrin...)
52

COOH HO NH2 NH2

HO

COOH NH2

tyramin
MeO HO

phenylalanin
O N H

tyrosin Capsaicin/ t Cay/thng mu

MeO MeO OMe NH2 HO

OH

Me

HO

Me

Me

Mescalin o gic

Ephedrin Vim xoang/m i

Hordenin Khng sinh 53

Nit co ngun t acid amin

COOH N H NH2
N H

N Me

Me

MeO O MeO MeO O N H

tryptophan
HO N H NH2

gramin
OMe
COOH N H NH Me

colchicin

Serotonin X ho tim

abrin
54

alkaloid kiu purin : theobromin, cafein, theophyllin

O Me N O N Me N N

O Me O N N Me N N Me
Me O N

O N N Me N

alkaloid kiu steroid : conessin, solanidin,

OH N
N

HO

conessin / M c hoa tr ng

solanidin / Solanaceae

55

ki u alkaloid terpenoid : aconitin, mesaconin, taxol

Paclitaxel = Taxol

kiu alkaloid peptid : ergotamin, ergocryptinin

56

s Nit :

- th

ng t 1

2 ( i khi > 2 Nit

dimer)

lo i vng: - a s : d vng Nit - m t s : vng carbon (protoalkaloid) s vng: - t khi 1 vng duy nh t (protoalkaloid) - th b c Nit : th - th ng 2 5 vng (strychnohexamin 15 vong)

ng l b c III (=N ), b c II ( NH ) 9.
57

ng co tinh kim; a s c pKa = 7

do

m i n c a Nit < Oxy p - lin k t N-H km phn c c h n lin k t O-H - lin k t hydro N...H l ng l o h n O...H - alkaloid km phn c c h n alcol t ng ng

i m si c a alkaloid so v i alcol t

ng ng :

alcol > alk I > alk II > alk III > ether tnh ki m c a alkaloid so v i ammoniac : NH4OH > alk IV > alk I > alk II > alk III ( NR2)
pKa = 9,3 > tnh ki m y u nh t dy
58

Hin nay, a bit > 27.000 cu truc alcaloid / 6000 loai th c vt (~20% th c vt bc cao).
   

Chu yu la th c vt bc cao, nganh hat kin. It g p alk / nganh hat trn, nm & quyt th c vt. Hu nh khng g p alk / TV bc thp (Ru, ia y, Tao) M ts ng vt, vi khun cung ch a alkaloid.
59

(NAPRALERT, 2005) 27000

1975-2005 : 22.000 ch t (02 alk / ngy)

(G.A. Cordell, 2001)

21200

(NAPRALERT, 1993)
16000

(Southon & Buckingham, 1989)

10000

1805-1975 : 5.000 ch t (02 alk / thng)

4000 300 400 500 1000 2000 5000

1920

1930

1940

1950

1960

1970

1975

1990

1993

2001

60 2005

5.1. Cac ho th c vt giau alcaloid Apocynaceae Rutaceae Amaryllidaceae Loganiaceae Ranunculaceae Papaveraceae Liliaceae Menispermaceae Asteraceae Berberidaceae Fabaceae Solanaceae Rubiaceae Euphorbiaceae Cataceae

Ch a tim thy alkaloid trong 4 b Salicales, Fagales, Cucurbitales, Oleales

61

M t s (~ 800) alkaloid t
       

ng vt

Samandarin, samandaron t Batrachotoxin t ch c

Ky nhng l a. (Phyllobates aurotaenia) (Bufo bufo) (Castor fiber) (Tetraodon spp.) (Ascaris suum, 2000) !!! (Glomeris marginata)

Bufotenin t tuy n da Cc (P)-castoramin t H i ly Tetrodotoxin t loi C cc Morphin t Giun heo Glomerin t Su bi Muscopyridin t H ux

(Moschus moschiferus)
62

M t s alkaloid t Alkaloid trong N m tryptophan.

N m (mushroom)

c sinh t ng h p t L-

T cc chi Psilocybe, Conocybe, Phanaeolus v Stoparia p serotonin, psilocin v psilocybin. y l cc alkaloid c tc ng ln h TKTW

Hai loi n m ch a psilosybin ng ch : - Psilocybe semilanceata - Phanaeolus subbalteatus

63

M t s alkaloid t T chi Lycopodium L. (D

ngnh Ru (moss) ng x )

p annotinin, lycopodin v cernuin. T loi Huperzia serrata v vi loi khc p huperzin A, J, K v L (c tc d ng / Alzheimer). p phlegmariurin v cc c a phlegmariurin B.

64

M t s alkaloid t - T Claviceps purpurea - T Claviceps sorghi - T Aspergillus terreus

vi khu n v vi n m (fungus) p ergolin, ergotamin, agrolavin p caffein (2003) p asterrelenin, terretonin,

- T Aspergillus fumigatus p agrolavin - T Penicillium janczewskii p 2 alkaloid quinolinon. - T Penicillium rivulum - T Penicillium citrinum - T Pseudomonas spp. p communesin G, H p perinadin A v citrinadin A, p tabtoxin v pyocyanin
65

5.2. Cac b phn ch a alcaloid Trong cy, alk. th Hat La ng tp trung c 1 s b phn nht inh Qua Hoa R Cu : Anh tuc, Tiu, : Ca d c t

: Ma tin, Ca d : Tra, Thuc la

Thn : Ma hoang Vo thn : Canhkina Hanh : N hoang cung

: Ba gac, L u : Binh vi, Bach b

Hat thuc phin : khng co alkaloid.

66

5.3. S Th Th

a dang va chuyn bit ng la 1 hn h p gm cac alcaloid cung nhom. ng co 1-2 alcaloid chinh (ham l ng cao nht).

Cac cy cung ho th

ng ch a cac alc. cung nhom.

(Solanaceae p alcaloid co nhn tropan) Mt s ho (Rubiaceae ) ch a nhiu nhom alcaloid - cy Ca ph : alc. nhn purin

- cy Canhkina : alc. nhn quinolin - cy Ipeca : alc. nhn isoquinolin

67

Tom lai trong 1 ho : co th g p nhiu nhom alcaloid. cung 1 ho : hy vong co cac alcaloid cung nhom. cung 1 chi : rt hy vong co cac alcaloid cung nhom. cung 1 alk. : co th g p nhiu ho khac h n nhau.

Him khi alcaloid va tinh du ng th i hin din.

68

Berberin c trong 27 chi thu c >10 h khc nhau :

1. Berberidaceae 2. Fumariaceae 3. Hydrastidaceae 4. Juglandaceae 5. Menispermaceae

6. Nandinaceae 7. Papaveraceae 8. Ranunculaceae 9. Rubiaceae, Fabaceae 0. Rutaceae

69

Trong ho Amaryllidaceae p 30 chi co Lycorin

Amaryllis Ammocharis Brunsdonna Buphane Calortemma Chlidanthus Clivia Cooperia Crinum Curcoligo Cyrtanthus Elisena Eucharis Eurycles Estephia Galanthus Haemanthus Hippeastrum Hymenocallis Leucojum Lycoris Narciscus Nerine Pancratium Sprekelia Sternbergia Ungernia Urceolina Valotta Zephyranthes
70

Caffein co trong nhiu cy 1. Tra 2. C ph 3. Mate (Camellia sinensis L., Theaceae) (Coffea spp., Rubiaceae) (Ilex paraguariensis, Ilex vomitoria, Aquifoliaceae) 4. Guaran 5. Cola 6. Citrus (Paullinia cupana, Sapindaceae) (Cola acuminata, Sterculiaceae) (Citrus spp., Rutaceae; bao ph n)
71

5.4. Ham l

ng alcaloid : ng, sinh ly cua cy. )

Thay i theo iu kin dinh d noi chung, [alkaloid] th t alcaloid :d

ng th p (#

i 1% (Wagner, 1996) 1% (berberin: 2-3% / Vang ng)

nhiu Vai tr

alcaloid : ng h p

c bit 6 10% alcaloid 30% alcaloid

72

- vo thn Canhkina ch a

- nh a Thuc phin ch a 20

5.5. Dang alcaloid trong cy dang base

(# 0)

dang mui
( as )

dang glycosid
(it)

v i acid v c (it) v i acid h u c thng th v i acid h u c c bit ng

- acid meconic, tropic, aconitic - acid gallic, tannic; tannin

73

6.1. Ly tinh a s [C,H,O,N] p r n / tO th (tr arecolin; pilocarpidin) ng kt tinh mp ro rang (nu bn tO) c

a s [C,H,

N] p long /

tO

th

ng

bay h i bn nhit, ct keo

c, c

(tr sempervirin, conessin)

74

Trong t nhin, cc alkaloid th - mui : th - vi : th ng khng mui ng ng

ng c. . .

(piperin, capsaicin cay; aconitin khng - mau : th ng khng mau

ng !!!)

(berberin, palmatin, chelidonin: mau vang jatrorrhizin mu - [E]D : th - pKa : th 2) ng ta trin ng t 7 9 (nn ki m ha v pH = pKa +
75

cam, pyocyanin mau xanh)

Ni chung, cc alkaloid base : 1. c phn c c trung bnh p ph.c c trung bnh n y u;

- alk. base tan / dmhc c

- nh ng kh tan / cc dmhc qu km ph.c c nh EP, n6. - p d ng chi t & tinh ch (ki m ha, bi n alk. mu i p alk. base, chi t alk. base b ng Bz, DCM, Cf, Et2O...) 2. c tnh ki m p d b ko v t trn b n si-gel pha thu n (Si-OH). kh c ph c : thm ki m vo pha 3. km b n (nh t l khi + tO) p nn chi t d i d ng alkaloid mu i (b n h n)
76

ng, v t s g n.

th ng kem tan / n c d tan / dmhc kem phc c (tr cafein, nicotin, coniin, colchicin, spartein tan / n d tan / n c kem tan / dmhc kem ph.c c ( EP) (tr berberin clorid, berberin nitrat kem tan / n c reserpin.HCl lai tan / CHCl3) alcaloid phenol : dang base vn tan (morphin, cephaelin) alcaloid mui :

alcaloid base :

c)

c / d.dich kim
77

Strychnin - kh tan trong ether - d tan trong CHCl3. - r t d tan / h n h p Et2O - CHCl3 (1 : 1) M t s alcaloid (ephedrin, cafein) c th th ng hoa p dng pp th ng hoa c p su t th tinh ch ng

(tr n b t tr v i vi, un / ct),

78

6.2.

Hoa tinh
N Me

COOH N H

COOH

6.2.1. Tinh ki m
ki m m nh ki m y u

(*)

(**)

ki m r t y u khng ki m cafein colchicin ricinin theobromin

acid y u arecaidin* guvacin** isoguvacin

nicotin

AS

codein piperin

alcaloid + acid ng alcaloid + thu c th chung

p mui t

ng

alcaloid + mui kim loai n ng p mui ph c q p tua hay mau

79

Alkaloid base co tinh kim y u h n cc ki m v c . [alk mui] se gi i phng ra [alk base] b i Na2CO3, amoniac, M(OH)n [alk.H]+.X + OH [alk] + (X /H2O)

N u alcaloid c 2 Nit (2 ch c base) : - c 2 N u co tinh kim : c th t o 2 lo i mu i. V d : Quinin p Q.HCl v Q.2HCl - 1 N c tinh base qu y u : ch co th t o 1 lo i mu i. V d : Strychnin p (Str)2SO4
80

alcaloid (pKa) berberin 2.5 caffein 3.6 acid acetic 4.8 reserpin 6.6

alcaloid (pKa) pilocarpin 7.0 vinblastin 7.4 heroin 7.6 scopolamin 7.7 quinin, brucin 7.8 quinidin, codein 7.9 strychnin 8.3 cocain 8.6

alcaloid (pKa) morphin 9.2 & 7.9 ammoniac 9.3 -ephedrin 9.4 ephedrin 9.6 amphetamin 9.9 atropin 10.2 nicotin 11.0 & 6.2

81

pH = pKa + 3 p > 99.9% pH = pKa 3 p > 99.9%

d ng alk. base d ng alk. mu i

n u SKLM 1 alkaloid # 50% m u # 50% m u

pH # pKa th :

d ng alk. base (km phn c c; Rf cao) d ng alk. mu i (phn c c h n; Rf th p)

v t b ko di, c th tch thnh 2 nhm v t

c n thm ki m

n pH = pKa + (2

3)

82

SKLM alkaloid / Si-gel NP v i pha ng c pH << [pKa

2]

alk.base, km phn c c h n, b ko v t.

alk.mu i, phn c c h n, v t g n h n.

Ngoi c n ch

phn c c c a pha

ng,
83

n pH khi SKLM alkaloid !

pH c a m t s dung d ch alkaloid
pH 3 4 5 5 5.5 6 4 6.5 6 pH 7

papaverin HCl codein phosphat eserin sulfat eserin salicylat ephedrin HCl caffein base quinin sulfat quinin HCl

5.5
84

6.2.2. Phan ng tao tua (Y/N) t a v Valse-Mayer Bouchardat nh hnh Dragendorff acid tannic t a tinh th - AuCl3 - PtCl3 - acid picric (Hager) - acid picrolinic Reineckat Scheibler (ac. phospho-tungstic) Sonnenschein (ac. phospho-molybdic) - acid styphnic - thth Marm (CdI2-KI)
85

Bertrand (silico-tungstic)

thth Bouchardat = thth Wagner (Iod / KI)

thu c th Bouchardat ValseMayer

thnh ph n KI + I2 KI + HgI2

t o t a v nu, nu

nh hnh mu

bng tr ng p vng ng cam p tr ng p vng (c th k tinh)

Dragendorff KI + BiI3 Marm Bertrand Tannin KI + CdI2

acid silicotungstic tr ng p tr ng ng acid tannic tr ng (tan / c n, AcOH, NH3)

86

thu c th

thnh ph n

t a v

nh hnh mu

Reineckat

h ng, tan / aceton 50% ammoni tetrasulfocyanid ( nh l ng o mu) diamin chromat III c th k t tinh d ng kh c tr ng, mp r ( nh danh) acid phospho-tungstic acid phospho-molybdic Co(SCN)2 tr ng tr ng xanh
87

Scheibler Sonnenchein Cobalt thiocyanat

nh y thay

i ty lo i thu c th , ty lo i alkaloid

Thu c th km b n / ki m (dd ch th : tr.tnh p acid nh ) T a c th tan l i trong - thu c th th a, trong MeOH, EtOH : Marm - thu c th th a, trong MeOH, EtOH, AcOH : Mayer - MeOH, EtOH, AcOH, NH4OH : acid tannic T a c thnh ph n n (p nh l nh

ng b ng ph.php cn gin ti p) : Bertrand

88

Johann Georg Nol Dragendorff (1836 1898)

89

Mt h p cht khng-alkaloid se (+) v i thu c th Dragendorff khi tai nhom ch c Oxy va carbon- (ni v i 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 se phan ng (+) v i th th Dragendorff. min la s m t tai nguyn t Oxy va tai carbon- nay

khng bi giam i (do hiu ng rut in t ho c do ni cu hydro)

90

alkaloid quinin morphin caffein

Valse-Mayer 8 ppm 400 ppm

Bouchardat

Dragendorff

100 ppm

1700 ppm

91

Alkaloid Morphin Apomorphin Papaverin, Thebain Codein, Heroin, Dionin Narcotin Narcein (km nh y)

Dragendorff 50 g 20 g 10 g 10 g 50 g

Zaffaroni * 10 g 10 g 10 g 20 g 50 g

*(thu c th Zaffaroni = Kali Iodo-Platinat)

92

thu c th Vng clorid Platin clorid acid picric acid styphnic acid picrolonic

thnh ph n AuCl3. HCl PtCl4. 2HCl 2,4,6-trinitrophenol 2,4,6-trinitroresorcin c a p-nitrobenzen

t o t a k t tinh c mu thay i

ty lo i alkaloid

c mu vng p c hnh d ng c i m ch y xc

cam c tr ng nh

93

NO 2 NO 2 OH NO 2 NO 2 HO

NO 2 OH NO 2
NO2

O NO2 N N Me

acid picric

acid styphnic + alkaloid - mu vng p cam c tr ng nh

acid picrolonic

tinh th c

- hnh d ng

- i m ch y xc

nh danh alkaloid
94

7.2.3. Phan ng v i thu c th th thu c th

c hi u ( nh danh)

ng kt h p v i SKLM // alcaloid chun thnh ph n Alkaloid Conessin s cho mu vng p xanh p l c tm tm xanh p xanh ng c tm xanh tm mu n
95

Erdmann acid sulfo-nitric Frohde

acid sulfo-molybdic Morphin Strychnin Codein Morphin Indol Brucin

Mandelin acid sulfo-vanadic Merke Marquis Wasicky HNO3 acid sulfo-selenic sulfo-formol sulfo-PDAB acid nitric .

Tc nhn: cc ch t c tnh oxy-ha m nh (acid sulfuric Mi tr ., acid nitric ., sulfochromic...) ng l khan. nh danh alk.

ng th c hi n : th

Cho s n ph m mu kh chuyn bi t, gip Mu th Mu thay ng km b n (quan st nhanh) i ty cc i u ki n ph n ng

(tO, pH v nh t l m c

tinh khi t c a m u alkaloid).

96

7.1. Nguyn t c chung Alk la cac base yu, trong cy co th - alk. ph c h p bn v i tannin Nu mun chit ngay d dang

- alk. mui v i acid h u c , v c (d chuyn dang) (kho chuyn dang)

i dang alk. mui :

Chit tr c tip [Alc.H]+.X v i dung mi thich h p Nu mun chit d i dang alk. base :

cn dung kim (tr.binh / manh) tao phan ng : [alk.H]+.X + OH [alk] + (X /H2O)

97

98

7.2.

Cac ph

ng phap chit xu t alkaloid

7.2.1. Chit dang alcaloid base - xay bt d c liu (khng qua min)

- lam m v a u v i kim thich h p (m nh, y u) - chit b ng dmi hc kem ph.c c (DCM, Cf, Bz ) - thu hi dung mi; tinh ch (lo i t p); kt tinh Khi lm m, trnh trnh un nng (c d c li u t qu

) d ch alkaloid base (khng b n). nh l ng).

99

thch h p khi thao tc nhanh ( nh tnh,

khng s d ng cho chi t xu t (ng m ki t lu / ki m).

7.2.2. Chit dang alcaloid base bay h i - xay bt d c liu (khng qua min)

- lam m v a u v i kim thich h p - chit b ng ph - th ng phap suc h i n c ng ngay.

ng dung cho inh tinh, inh l

100

nhit k va b tip n c h in c si Alk base ng ng tu

c liu + kim

dung dich acid loang

101

7.2.3. Chit cac alcaloid base th ng hoa - xay bt d c liu

- lam m v a u v i kim thich h p - un nong b ng nhit kh (cch ct ) - thu tinh th alc. base v a th ng hoa - tinh ch, kt tinh V d : Chi t Cafein t b t Tr cm, tr v n.

102

7.2.4. Chit dang alcaloid mui - xay bt d c liu (khng qua min) c acid)

- lam m v a u v i dung mi chit, n p vo bnh - chit b ng dung mi (cn / cn acid / n - c thu h i b t c n. - tinh ch (loai tap + chuyn dang); kt tinh Ph ng php ny c th p d ng cho s n xu t

v i quy m trung bnh p l n.

103

PH

NG PHP STAS-OTTO (1850)

- Alkaloid mu i : tan / ROH, khng tan / Et2O. - Alkaloid base : tan / Et2O. (tr morphin base). 1. Chi t l y alkaloid mu i b ng ROH / acid. 2. R a d ch [ROH / acid] v i Et2O lo i t p km phn c c.

3. Trung ha d ch [ROH / acid] v i soda (natri carbonat). 4. L c l y ph n tan trong Et2O; c Et2O, thu alkaloid base.

104

PP. STAS

OTTO (1850)

ban

u: c

c n - acid tartric q t p b ng n dmhc l Et2O, CHCl3 hi n nay : acid thay dmhc thay i i lo i t p = dmhc / H+
105

8.1. Lo i b t p mu b ng than ho t tnh c n th m d t l C* t m t alkaloid. 8.2. Chuy n d ng alk mu i p alk base ch n lo i ki m NH4OH, Na2CO3, NaOH, Ca(OH)2 ch n pH thch h p (pH = pKa +2) ch n dmhc Bz, Et2O, DCM, Cf, Cf 8.3. Chuy n d ng alk base p alk mu i ch n lo i acid (sulfuric, HCl, AcOH, tartric) ch n pH thch h p (pH = pKa 2)
106

Et2O (3 : 1)

ch n dung mi (EtOH, MeOH, HOH)

L u khi tinh ch - alk. base b c IV (berberin) - alk. phenolat (morphin) - nicotin base, cafein base cch phn l p chuyn bi t i v i h n h p {alk ki m y u + alk ki m m nh}: c th - ki m ha l n 1 v i NH3, l c v i dmhc (thu alk ki m y u) - ki m ha l n 2 v i NaOH, l c dmhc (thu alk ki m m nh)
107

tan

c trong n

Ph

ng phap SKLM ch ha (p-TLC)

vung khng phun thuc th

vung phun thuc th

(A)

vung phun thuc th

(B)

(C)

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

108

Ph

ng php s c ky ct (SKC)

a. SKC hp phu cht h phu : Si-gel (15-40 hay 40-63 m) co th nhi Si-gel v i d.dich m kim mu nap khai trin : alcaloid base : hay dung CHCl3 (it tap); k ~ 30 MeOH (x : y) 60

sao cho Rf ~ 0,30 / SKLM 1 ln theo doi : SKLM / UV 254 nm hay / Dragendorff

thu phn oan tinh khit, kt tinh p alcaloid base.

109

Ph

ng php SKC

b. SKC ry phn t Th ng s d ng pha t nh l Sephadex LH-20 MeOH)

M u th : alk. base ton ph n cn l n t p / (Cf Khai tri n v i MeOH, MeOH CHCl3 c

- cc h p ch t c MW l n s ra tr

- cc h p ch t c MW nh s ra sau.
110

Ph

ng php SKC o

c. SKC phn b Th

ng dng pha t nh Diaion HP-20 (Mitsubishi). H2O)

M u : alk. mu i ton ph n cn t t p / (MeOH Khai tri n c t v i (H2O

MeOH) (100 : 0 p 0 : 100) c

- cc h p ch t phn c c m nh h n : ra tr - cc h p ch t phn c c y u h n : ra sau

111

9.1. Trn vi phu (ph n ng ha m)

vi ph u 1 r a b ng c n tartric khng r a r i + thu c th Bouchardat c t a nu K t lu n p c protein / alcaloid. (th ti p vi ph u 2 v 3) p c protein; alk ???

c r a

v n c t a nu

c r a

khng cn t a nu

p c alcaloid.

- alcaloid va protein u cho tua v i th th Bouchardat - alc. tan / cn tartric; protein khng tan / cn tartric.
112

9.2. B ng ph Muc ich

ng php s c k

- co alkaloid ??? - co d - ham l c liu A, B, C ??? ng x, y, z ??? - co alkaloid x, y, z ???

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

9.2.1. Trn SKLM Ban mong : Si-gel F254, RP-18 (Merck mu chm : alk base dung mi phat hin : th )

(it tap) / CHCl3 (chm vach)

ng thm kim (h u c , v c ) y u *

: UV 254 nm / Dragendorff / th th khac n pH p (pKa + 2)

* Thm ki m

p lam gon vt alkaloid (tranh keo vt) * Ky thut thm ki m - tm vao giy bao hoa binh s c k - tm vao pha tinh; thm ngay vao h d.mi
114

H dung mi (2 phn c c km EP, n-6, n-7 Tol, Bz, Et2O Cf, DCM

3 thanh phn) phn c c tr.bnh EtOAc Me2CO AcCN phn c c m nh n-BuOH i-PrOH EtOH, MeOH

Nguyn t c chung: Dung mi // Mu th (alkaloid) Dung mi th - NH4OH ( ng thm kim yu (pH modifiers) p %), dimethyl formamid (DMF)
115

- diethylamin, triethylamin (DEA, TEA)

Mu th - th - mu ng la alkaloid base (toan phn, phn oan) c hoa trong Bz, Cf, DCM.

- nn chm thanh vach (1 mm 5-10 mm) - mu cao h n m c dung mi ~ 5 mm - khai trin 1 ln, n ln; chiu khai trin: o Phat hin vt - soi UV 254 (t t quang) / 365 nm (phat quang) - h h i Iod (cc alk. co - phun / nhung thu c th / cu truc) c hiu (t s d ng). - phun / nhung thu c th Dragendorff **
116

9.3. B ng ph n ng ha h c L u y : khi lam cac ph. ng tao tua / mau nn th c hin v i cac d.dich alk. mui
nh gi ( ) (+) (++) (+++) (++++) v n trong c l , khng l ng c nhi u, t a xu t hi n sau vi pht t a r, l ng nhanh; thm 1 gi t TT p t a ti p t a nhi u, l ng ngay; thm 1 gi t TT p t a ti p
117

Quan st th y dung d ch

9.3. B ng ph n ng ha h c

118

Mt s phan ng mau
alcaloid Tropan Strychnin Brucin Cafein ph n ng mu Vitali-Morin Sulfo-chromic Cacothelin Murexid

c hiu thng dung

alcaloid Berberin Quinin Quinin Quinin ph n ng mu Oxyberberin Thaleoquinin Erythroquinin Hu nh quang

119

Nguyn t c chung alk. mui / d c liu

alk. mui / d.mi tap

thay i pH

alk. base / d.mi tap

c n alk. base sach

1. p.phap cn 2. acid base

3. o quang 4. pp. s c ky
120

10.1. Ph

ng phap cn : p d ng khi ng = acid-base c (alk. kim qua yu)

P b (kho cn)

- khng .l

- alkaloid ch a ro v cu truc hoa hoc - hn h p ph c tap cua nhiu alkaloid - mun anh gia s b v M c tin cy - kem chinh xac (alk% qua it; tap th a) - kh c phuc = ph tip ng phap cn gian
P l n (d cn)
121

alkaloid

10.1. Ph

ng phap cn

chit dang alk. acid ho c base cafein, nicotin loai tap (cht beo, tannin ) Bertrand Bertrand.(alk)4

i pH nhiu ln (chuyn dang)

alkaloid base Palkaloid cn tr c tip, gin ti p (cn gin ti p) 122

10.2. Ph.phap th tich

alk. base acid th a (HCl, H2SO4 loang)

kim

v i cac chi thi mau vng pH acid : - methyl o (4.2 o p 6.3 vang) - methyl cam (3.0 o p 4.4 vang) (co th + methylen xanh)
123

10.2. Ph.phap th tich (m.tr - nn: AcOH b ng - acid percloric th a - chi thi mau: Tim tinh th

ng khan)

- ap dung: k c alk. kim qua yu (cafein, colchicin ) - chinh xac > ph.phap cn

tim tinh th : vang luc (acid) p xanh luc (tr.tinh) p tim (kim)
124

10.3. Ph

ng phap o mau

- mau t nhin (berberin, palmatin) - mau do + th th tao mau (Dragendorff, oxy-hoa) - mau huynh quang (quinin sulfat) Th c hin - o tr c tip t dung dich mau hay quy v 1 alkaloid ai din - o do quet vt mau (scanner / SKLM) th ng lam // alkaloid chun
125

10.4. Ph

ng phap SKLM SKLM tao mau o vt [alkaloid %]

din tich vt c ng mau cao vt scanner

10.5. Ph Th

ng phap HPLC
126

ng kt h p v i nhiu cach ch.bi mu (SPE, SPME)

v i nhiu detector khac nhau (UV, IR, RI, MS, ELSD...)

L nh ng ch t chuy n ha th c p, ch t bi ti t ho c l s n ph m cu i trong qu trnh chuy n ha c a th c v t. L nh ng ch t d tr Nit , tham gia vo chu trnh Nit trong th c v t. i khi l nh ng ch t tch l y d n t th c n (Ki n l y alk. t l cy; ch, Cc n ki n p ch, Cc c alk.) L nh ng ch t b o v , ch ng cc sinh v t n th c v t. L v kh ha h c trong t v , c n trong qu trnh sinh t n nh t l ng v t (C, Cc, K nhng ...)
127

Alkaloid th

ng c ho t tnh sinh h c m nh c s d ng trong y h c.

n r t m nh

kh nhi u ch t

m t s ch t dng lm ch t (tubocurarin / Curar) m t s ch t qu

c dng trong s n b n

c, khng dng trong y h c ng nguy h i n x h i

(Gelsemin trong L ngn). nhi u ch t c thm tc (gy nghi n, ma ty, o gic) If Nature had any sense, She wouldn t make alkaloids !
(John Comforth) 128

Khi th c v t c nhm alkaloid, th tc d ng c a d th ng do nhm alk. (trong th Trn h th n kinh - kch thch TKTW - c ch TKTW - li t tr c giao c m - li t ph giao c m : cafein, strychnin : morphin, codein : yohimbin : atropin

c li u

ng do 1 alk. ch y u).

- kch thch tr c giao c m : ephedrin - kch thch ph giao c m : pilocarpin

129

Trn cc c quan khc - Gy t - Gi m ho : cocain : Codein - Gi m au : morphin

- Gi m co th t : Papaverin - Di t giun sn : Arecolin

- Tr s t rt : Quinin

- Di t khu n : Berberin, Emetin - H huy t p : Reserpin - Tr 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.

p Mescalin
132

Alkaloid t

ng v t ng v t, nh t l B nhi u chn, Cc, ch, C,

Alkaloid c ng c trong K nhng v

ng v t c v (Saxidomus, Salamandra, Phyllobates,

Dendrobates, Castor, Moschus, Solenopsis, Glomeris, Odontomachus v Polyzonium). Trong h i sinh v t, c bi t t cc loi H i min (Ptilocaulis spiculifer,

Hemimycale spp., Crambe crambe, Monanchora arbuscula, M. ungiculata) tch c cc alkaloid guanidin (batzelladin J,

ptilomycaulin A, ptilocaulin v isoptilocaulin) Sao bi n (Fromia monilis v Celerina heffernani) c ng c alkaloid.

133

Alkaloid c ng c B Anura

da 1 s loi l

ng c . C 3 b l

ng c :

v i > 4500 loi Cc, ch, v i > 450 loi k nhng, th n l n, v i > 160 loi su khng chn.

B Urodela B Apoda

T da Anura species, Osteocephalus taurinus, O. oophagus v O. langsdorfii p bufetenin c tnh gy o gic ki u LSD. T da cc Melanophryniscus montevidensis p nhm pumiliotoxin (PTX) v alkaloid nhm indolizidin.

134

The lady bird (Coccinellidae) v Ong c ng ch a alkaloid. M t s loi b m m Utethesia ornatix thu alkaloid pyrrolizidin khi cn g c cc loi Crotalaria (Fabaceae).

l u trng s ng

Longitarsus lateripunctatus, 1 loi ong do n l cy Pulmonaria abscura, c ng ch a alkaloid pyrrolizidin. Cc loi ki n Anochetum grandidieri v Tetramorium electrum, ch a alkaloid pyrrolizidin, c tm th y trong d dy ch Mantella. ng

ch Dendrobates pumilio ch a alkaloid dendrobatid l do n cc v t chn t tch l y cc alkaloid ny. c tm th y

Vi alkaloid pyrroloindol (pseudo-phrynaminol) Pseudophryne coriacea.

loi ch
135

Hi n c h n 800 alkaloid c TDSH c Tr tr d

c tm th y t da cc loi l

ng

ng h p 2 nhm samandarin v pseudophrynamin, u c ngu n t th c ph m.

ng nh t t c cc alkaloid cn l i ong ki n, m i ki n ki n

p batrachotoxin v coccinelline-like tricyclics p pumiliotoxin. p decahydroquinolin, izidin, pyrrolidin v piperidin. p histrionicotoxin, lehmizidin and tricyclic gephyrotoxin

136

T Bryozoan (Flustra foliacea) p nhi u brom-alkaloid nhm indol nh flustramin, deformylflustramin, deformylfrustrabromin A, B. T s a D n l cy Erythrinia poeppigiana p erythrinan alkaloid ( -erythroidin v dihydro- -erythroidin) c tc d ng ki u curare. Cc nhm alkaloid ng v t bao g m t nhm isoquinolin, -carbolin,

n thiazolidin, arising from vitamin B6, chloral and glyoxylic acid. T lu, ng i ta v n cho r ng cc alkaloid tetrahydro-isoquinolin

v n c ngu n g c t th c v t. Tuy nhin, c ng c tc gi coi chng l cc alkaloid n i sinh t nhin t c th ng i v ng v t.

137

6. Phn lo i:
 Pyridine  Pyrolidine pyridine  Quinoline  Isoquinoline  Phenantrene  Indol.
138

6.1 Nhom pyridine:

Sn c ban
4 5 6 3 2

N
1

139

Nhom pyridine: Trigoneline (C7H7O2N) trong hat Ca phe

COO Ba(OH)2 N Cl CH3 HCl, P COOH CH3Cl N Acid nicotinic ( acid piridin_3_carboxilic)
140

CH3NH2

Tong hp trigoniline (PP HANTZSCH)

COOH MeI N KOH, T N I Me COOMe AgOH T N OH COOH ( H2O) N Me Trigonelin COO

Me

141

Ricinine (C8H8O2N2) trong hat Thau dau

OMe CN N Me
142

Nh ng alkaloid co trong h t 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 (Punica granatum) h Punicaece

N HO

Peletierine
146

N H

CH2

C O

CH3

Isopeletierine
147

Nhng alkaloid co trong hat tieu en (piper nigrum) ho Piperaceae

N O C H C C H H C C H O O

Piperine
148

Piper nigrum L.

149

Nhm Pyridine:


5 6

3 2

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 (nicotiana tabacum) ho Solanaceae

151

N N CH3

Nicotine
COOH COOH N
Acid nicotinic ( Pyridine_3_carboxilic) (Pryridine_4_carboxilic)

COOH

N
Acid isonicotine

Acid picolic ( Pyridine_2_carboxilic)

152

N N CH3 N

N H Nor _ Nicotine

Nicotyrine

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 153 cha 2% nicotine.

6.3 Nhng alkaloid thuoc nhom quinoline



Alkaloid cua vo cay quinquina (cinchona Rubiaceae): Co hai alkaloid quan trong : quinine va cinchonine..
5 6 7 8 4 3 2

N
1
154

155

Cinchona succirubra P. (Cy canhkina)

156

10 5 3 6 2

11

H
9

7 8 3' 2'

CH

CH2

H3CO
7'

6'

HO 5'

C
4'

N
1

8'

N 1'

157

158

159

C3 nhom etilen C6 nhom metoxi 9nhom hidroxi C9

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

161

10 5 3 6 2

11

4 7 5 9 6' 7' 8' 5' 4' 8 6 3 2

H
9 6' 7' 8'

7 8 3' 2'

CH

CH2

HO 5'

C
4'

N
1

N
3' 2'

N 1'

N 1'

Cinchonine

Ruban
162

Cinchonine

163

164

165

C cau lap the cua quinine, quinidine Cinchonine, cinchonidine.

H2C CH
2 4 7 8 5 7 3

H2C CH
2

H2C
3 4 5

CH
2 7

3 4

H
5

H C HO
8

N 1 C9 H

H
6 8

N
1

N 1 C
9

HO Q

HO

Q H

H Q' '

Q' '

H3CO

Vi Q=
N

Vi

Q=

N
166

6.4 Alkaloid thuoc nhom isoquinoline:

5 6 7 8 1 4 3

167

Papaver somniferum L. (Cy thu c phi n )

168

169

Alkaloid c trch t cay a phien co nhan isoquinoline: Papaverine, laudanosine, laudanine

H3CO H3CO H3CO
1'

H3CO N CH3

N CH2
6' 5' 2' 3' 4'

H3CO
1'

N CH2

CH3

H3CO CH2 1'

6'

2' 3'

6' 5'

2' 3'

5'

OCH3

4'

OH

OCH3

4'

OCH3

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.
HO
4 2 3 1 11 12 5 13 14 16 8 7 10 9

O H H HO
6 15

CH3

(C17H19O3N)

173

Morphine

174

H3CO

H3CO

O H H OH N CH3

O N CH3

OCH3

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 2 3 4 6 9 7 8

N H

177

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

17 18

R1

1 6 7

16

V
20 21 22

I R2
3 4 5

II
9

N 19 15 IV VI
13 14 12

10

III

VII O
23

11

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

178

Trychnine

179

Trychnos ( h Loganiaceae)

180

Strychnos nux-vomica L. nux(Cy m ti n)

181

Alkaloid cua chi Rauwolfia, ho Apocynaceae:

Ajmaline, Ajmalicine, Serpentine, Reserpine, Yohimbine. Yohimbine.

9 10 8 13 7 3 6 5

H3CO

11 12

N
1

H H3COOC OCH3 O C O

OCH3 OCH3 OCH3

Reserpine (C33H40O9N2)

182

Reserpine

183

184

Rauwolfia serpentina

185

Yohimbine ( C21H26O3N2)
9 10 8 13 11 12 7 3 6 5

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): 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 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 25g Nc cat 1000ml 1000ml * Thuoc th Valser HgI2 Lng tha KI 10g 10g Nc cat 100ml 100ml e yen va loc
194

Iodur Bismuth va K Thuoc th Dragendorff

Bi(NO3)3 trung hoa HNO3 am ac KI Nc cat 20g 20g 30g 30g 68 250ml 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 1,5g KI 7g HCl am ac 20 giot Nc cat 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 HNO :
3

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. alkaloid.

4. Tnh ch t
 Alkaloid

la chat co trong lng phan t kha ln.

 Cha oxigene thng la chat

Alkaloid thng khong mau, v ang va co tnh trien quang .



ran, ket tinh, khong loi cuon bi hi nc.