Tp ch Ha hc, T. 43 (5), Tr.

586 - 589, 2005

Cc hp cht aporphin ancaloit t cy Kho

(S l to), Phoebe tovoyana (Meissn.) Hook. f.
(h long no)
n Ta son 17-2-2005
Nguyn Vn Hng, Nguyn Vn Tuyn
Vin Ha hc, Vin Khoa hc v' Cng ngh Vit Nam
Summary
In continuation of our interest in discovering biologically active compounds from plants of the
Vietnamese flora, in this paper we describle the chemical investigation of the bark of Phoebe
tovoyana (Meissn.) Hook. f. (Su la to, Lauraceae), collected in Nhuxuan district, Thanhhoa
province. Seven known aporphine alkaloids as Corydin, N-methyllaurolitsin, Nmethyllaurotetanine, pronuciferine, stepharine, norcorydine and anonaine were isolated from the
stem bark of this plant. The structures of these compounds were elucidated by spectroscopic
methods.

I - M u
Aporphin ancaloit l lp cht thin nhin c
hot tnh sinh hc l th. Mt s aporphin
ancaloit c kh nng khng khun, khng nm,
chng k sinh trng *ng mu, chng lng
ng tiu cu v hot tnh chng ung th*. Cc
hp cht n y th*ng *c tm thy trong trong
cc chi Kho (P. pittieri, P. Chinensis ...). Cho
n nay, trn th gii 8 c mt s cng trnh
nghin cu v cc chi kho (P. molicella, P.
pittieri, P. formosana, P. valeriana, P.
grandis...) thuc h long n8o [1 - 7]. Ng*i ta
8 phn lp v xc nh cu trc ca rt nhiu
aporphin ancaloit t cc chi n y. Trong cng
trnh tr*c y, chng ti 8 cng b v vic
chit tch cc aporphin ancaloit t cy Kho
Chun (Phoebe chinensis), cng nh* hot tnh
gy c t b o trn cc dng t b o ung th*
ng*i ca cc aporphin ancaloit tch *c t
cy n y [8]. Tip tc cc cng trnh nghin cu
v vic tm kim cc hot cht c hot tnh sinh
hc t cc chi Kho, trong b i bo n y chng ti
gii thiu mt s kt qu v phn lp, xc nh
586

cu trc ha hc ca mt s aporphin ancaloit t

mt lo i Kho khc l cy Kho (S l to), Bi
bi cm (Phoebe tovoyana (Meissn.) Hook. f.).
II - Thc nghim
Thit b v nguyn liu
Ph cng h*ng t proton (300 MHz) v
cacbon-13 (75 MHz) *c o trn my Bruker
AC 300. Ph khi l*ng *c o trn my
Kratos MS-80 Mass spectrometer. Gc quay cc
[ ]D *c o trn my Perkin-Elmer 241
polarimeter.
Cy Kho (S l to) (Phoebe tavoyana
(Meissn.) Hook. f.) *c chng ti thu hi ti
Nh* Xun, Thanh Ha, thng 8 nm 1997. Tn
cy *c TS. Nguyn Hu Hin, Vin Sinh thi
v T i nguyn sinh vt, Vin Khoa hc v Cng
ngh Vit Nam xc nh. Mu tiu bn s
VN288 hin *c l*u gi ti Phng tiu bn
thc vt ca Vin n y.
Chit tch
V thn cy Kho (S l to) (0,4 kg) kh,

nghin nh, *c chit vi b soxhlet bng dung

mi CH2Cl2 trong 48 gi. Dch chit sau
*c ct loi dung mi p sut thp cho
dch chit th. Dch chit n y *c x l vi hn
hp 200 ml HCl 5% v 300 ml ete, nhn *c
mui ca ancaloit tan trong n*c. Dung dch
mui n y *c trung ho bng NH4OH, sau
chit bng CH2Cl2. Ct loi dung mi nhn *c
7,6 g ancaloit to n phn.
Cc ancaloit *c tch trn ct silica gel vi
h dung mi CH2Cl2 : MeOH thay i t*ng ng
(99 : 1, 98 : 2, 97 : 3, 95 : 5), nhn *c cc cht
1 - 7. Sau cc cht n y *c tch li bng sc
k lp mng iu ch vi pha ng l MeOH :
CH2Cl2 (5 : 95) nhn *c cc ancaloit sch.
Corydin (1): MS: m/z: 341 [M]+, [ ]25D =
+2020 (c 0,6, EtOH), nc = 148 - 149oC. 1HNMR (300 MHz, CDCl3) (ppm): 7,07 (1H, d,
J = 8,9 Hz, H-8); 6,84 (1H, d, J = 8,9 Hz, H-9);
6,73 (1H, s, H-3): 3,88 (6H, s, OMe); 3,73 (3H,
s, OMe); 2,59 (3H, s, N-CH3). 13C-NMR (75
MHz, CDCl3) (ppm): 29,3 (C-4); 35,8 (C-7);
44,2 (NCH3); 53,0 (C-6a); 56,2 (2x OMe);
62,1(OMe); 63,0 (CH2); 111,0 (=CH); 111,5
(=CH); 124,2 (Cq); 124,4 (=CH); 126,7 (Cq);
128,4 (Cq) 131,1 (Cq); 142,4 (Cq); 143,9 (Cq);
149,2 (Cq); 151,9 (Cq).
Pronuciferin (2): MS: m/z: 311 [M]+,
20
[ ] D = +99 o (c 0,2 trong CHCl3), nc = 127 129oC. 1H-NMR (300 MHz, CDCl3) (ppm):
7,03 (1H, dd, J = 10, 2 v 2,7 Hz, H-12); 6,83
(1H, dd, J = 10, 2 v 2,8 Hz, H-8); 6,62 (1H, s,
H-3); 6,39 (1H, dd, J = 10, 2 v 2,7 Hz, H-11);
6,31(1H, dd, J = 10, 2 v 2,8 Hz, H-9); 3,81
(3H, s, OMe); 3,62 (3H, s, OMe); 3,42-3,50
(1H, m, H6a); 3,15 - 3,19 (1H, m, H-5a); 2,783,10 (2H, m, H-5b, H-4a). 2,40 - 2,55 (1H, m,
H-4b); 2,34 - 2,39 (1H, dd, H-7a); 2,39 (3H, s,
N-Me); 2,25 (1H, dd, H-7b).
Anonain (3): MS: m/z: 265 [M]+, [ ]20D=
-20 (c 0,1 trong CHCl3), nc = 122 - 123oC.
1
H-NMR (250 MHz, CDCl3) (ppm): 8,10 (1H,
d, J = 8,9 Hz, H-11); 7,21 - 7,33 (3H, m, H-8,
H-9, H-10); 6,75 (1H, s, H-3); 6,07 v 5,93
(2x1H, s, O-CH2-O); 2,20 (1H, s, NH).13C-NMR
(62,5 MHz, CDCl3) (ppm): 23,7 (C-4); 34,3
(C-7); 43,0 (C-5); 53,0 (C-6a); 100,7 (O-CH2-

O); 111,3 (C-8); 112,7 (C-3a); 115,5 (C- 11);

116,2 (C-3); 117,2 (C-7a); 118,2 (C-1a); 125,6
(C-1b); 127,7 (C-9); 127,8 (C-11a) 129,2 (C10); 137,8 (C-1); 141,6 (C-2).
Norcorydin (4): MS: m/z: 327 [M]+, [ ]20D=
+190o (c 0,2 trong CHCl3), cht du. 1H- NMR
(300 MHz, CDCl3) (ppm): 7,22 (1H, , d, J =
8,9 Hz, H-9); 7,0 (1H, d, J = 8,9 Hz, H-8); 6,68
(1H, s, H-3): 3,98 (3H, s, OMe); 3,79 (3H, s,
OMe).
Stepharin (5): MS: m/z: 297 [M]+, [ ]20D =
+143o (c 1,87 trong MeOH), nc = 179 - 180oC.
1
H-NMR (300 MHz, CDCl3) : 7,03 (1H, dd, J
= 10, 2 v 2,8 Hz, H-12); 6,83 (1H, dd, J = 10, 2
v 2,8 Hz, H-8); 6,62 (1H, s, H-3); 6,39 (1H, dd,
J = 10, 2 v 2,8 Hz, H-11); 6,31(1H, dd, J = 10,
2 v 2,8 Hz, H-9); 4,24 - 4,38 (1H, m, H-6a);
3,81 (3H, s, OMe); 3,60 (3H, s, OMe); 3,603,74 (1H, m, H-5a); 3,15 - 3,22 (1H, m, H-5b);
2,68 - 2,79 (2H, m, H-4a, H-4b); 2,38 (1H, dd,
H-7); 2,24 (1H, dd, H-7); 1,80 (1H, s, NH). 13CNMR (62,5 MHz, CDCl3) (ppm): 26,2 (C-4);
45,0 (C-7); 48,3 (C-5); 51,1 (C-7a); 56,2 (OMe);
57,7 (OMe); 60,9 (C-6a); 112,2 (C-3); 127,3 (C11, C-1b); 128,1 (C-9, C-3a); 132,5 (C-1a);
135,5 (C-1); 144,3 (C-2); 149,9 (C-12); 153,4
(C-8); 186,1 (C=O).
N-metyllaurotetanin (6): MS: m/z: 341
[M]+, [ ]20D = +111o (c 0,8 trong MeOH), nc =
103 - 105o. 1H-NMR (300 MHz, CDCl3) : 8,04
(1H, s, H-11); 6,76 (1H, s, H-8); 6,57 (1H, s, H3); 3,84 (6H, s, OMe); 3,66 (3H, s, OMe); 3,64
(3H, s, OMe); 2,51 (3H, s, N-Me).
N-metyllaurolitsin (7): MS: m/z: 327 [M]+.
[ ] D = +128o (c 0,98 trong MeOH), nc =123 125 o. 1H- NMR (250 MHz, CDCl3) : 8,0 (1H,
s, H-11); 6,82 (1H, s, H-8); 6,61 (1H, s, H-3);
3,39 (1H, s, OMe); 3,89 (3H, s, OMe); 2,53
(3H, s, N-Me).
20

III - Kt qu v# tho lun

Cc ancaloit chit t v cy Kho (S l to)
*c tch ra bng ph*ng php sc k ct
(Silicagel 60H) vi hn hp dung mi ra gii
CH2Cl2/MeOH vi l*ng MeOH tng dn t 15%; sau *c l m sch bng sc k lp mng
587

iu ch (10% MeOH/CH2Cl2), nhn *c cc

ancaloit 1, 2, 3, 4, 5, 6 v 7 (cng thc hnh 1).
Cht 1 l mt cht bt m u trng, c pic ion
phn t trong ph khi ti m/z 341 [M]+,
(C20H23NO4). Ph 1H-NMR ch ra cc tn hiu
ca cc proton nhn thm H-3 ( 6,73 s), 2 tn
hiu c tr*ng cho proton H-8 ( 7,07,d) v H-9
( 6,84, d), cc proton c tr*ng cho ba nhm
MeO

3a

HO

1b
1

MeO

6a

1a
11a

7a

MeO

N6
H CH3

H2C

NH
H

8
9

11

MeO

6a N
Me

12

MeO 1

11

MeO 10

OMe ( 3,73; 2 3,88) v tn hiu ca nhm NMe ( 2,59, s). T cc d liu ph 1H-NMR
cng nh* ph 13C-NMR (xem phn thc
nghim) chng ti ngh cu trc ca cht 1 l
corydin. iu n y *c khng nh khi so snh
vi ph MS, 1H-NMR, 13C-NMR v [ ]D ca
cht corydin t i liu [9].
Cng t*ng t, khi nghin cu ph

NH

HO

MeO
MeO

2
MeO

MeO
NH

MeO

HO
N

MeO

H
MeO

CH3

N Me

MeO

MeO

OH

OH

Hnh 1
cng h*ng t ht nhn proton v cacbon-13 ca
cht 2, ng thi so snh ph ca n vi ph ca
pronuciferin [13] 8 xc nh cht 2 l
pronuciferin.
Cht 3 nhn *c l cht bt m u trng, c
pic ion phn t trong ph khi ti m/z l 265
[M]+, (C17H15NO2). Bng cch t*ng, t khi
nghin cu ph ca hp cht 3 chng ti thy
xut hin proton vng tr*ng thp, c tr*ng
cho H-11( 8,10, d) v 3 proton H-8, H-9, H-10
( 7,21 - 7,33 m), proton thm H-3 ( 6,75) v
hai proton ca nhm dioxymetylen ( 5,93, s).
Ngo i ra, khi so snh d liu ph ca n vi d
liu ph ca hp cht anonain [11, 12] c th
kt lun hp cht 3 l anonain.
Mt cch t*ng t, cht 4 *c chng minh
588

l norcorydin nh cc ph*ng php ph v so

snh cc d liu ph ca n nh* MS, 1H-NMR,
v [ ]D vi ph ca norcorydin 8 bit [9].
Cht 5 c pic ion phn t trong ph khi ti
m/z 297 [M]+ (C18H19NO3). Ph cng h*ng t
proton ca n c tn hiu ca cc proton thm
H-12 ( 7,03, dd), H-8 ( 6,83, dd), H-3 ( 6,62,
s), H-11 ( 6,39, dd), H-9 ( 6,31, dd), cc tn
hiu c tr*ng cho hai nhm OMe ( 3,81 v
3,60). So snh cc d liu v ph MS, 1H-NMR,
13
C-NMR v [ ]D ca n vi cht 8 bit
stepharin [14] cho php khng nh cht n y l
stepharin.
Cht 6 l mt cht bt m u trng, c pic ion
phn t trong ph khi ti m/z l 341 [M]+,
(C20H23NO4). Trn ph 1H-NMR ca n xut

hin cc tn hiu ca proton thm H-11 ( 8,04,

s), H-8 ( 6,76, s), H-3 ( 6,57, s), cc tn hiu
c tr*ng cho ba nhm OMe ( 3,84, 3,66 v
3,64, s), cng vi tn hiu c tr*ng cho nhm
N-Me ( 2,51, s). T cc d liu ph 1H-NMR
chng ti ngh cu trc ca cht 6 l Nmetyllaurotetanin. iu n y *c khng nh
khi so snh vi ph MS, 1H-NMR v [ ]D ca
cht N-metyllaurotetanin [10].
Cht 7 c pic ion phn t trong ph khi ti
m/z 327 [M]+ (C19H21NO4). Ph cng h*ng t
proton c tn hiu ca cc proton thm H-11 (
8,0, s), H-8 ( 6,82, s), H-3 ( 6,61, s), cc tn
hiu c tr*ng cho hai nhm OMe ( 3,39 v
3,89, s), cng vi tn hiu c tr*ng cho nhm
N-Me ( 2,53, s). So snh cc d liu v ph
MS, 1H-NMR ca n vi cht 8 bit Nmetyllaurolitsin [12] cho php khng nh cht
n y l N-metyllaurolitsin.
Tm li, bng cc ph*ng php sc k chng
ti 8 tch *c nm aporphin v hai
proaporphin ancaloit t v cy Kho (S l to
Phoebe tavoyana). Cu trc ca cc hp cht
n y *c xc nh nh s dng cc ph*ng
php ph cng h*ng t ht nhn, ph khi
l*ng v so snh vi t i liu cng b.
Li cm n: Cc tc gi chn th'nh cm n
Hi ng khoa hc t nhin (B Khoa hc Cng
ngh) I cp kinh ph NCCB thc hin vic
chit tch v' phn lp th'nh phn ha hc ca
cy Kho (S l to), D n hp tc Php VitVin Ha hc, Vin Khoa hc v' Cng ngh
Vit Nam I cung cp mu nghin cu v' chp
ph NMR cc cht phn lp Vc.

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