T9P chiDtr^c li^u, tgp 18, sd 2/2013 (Trang 93 - 96)

H A I ANTHRANOID PHAN LAP DlTgfC T f R E BA K I C H

^Tran Thi J'^" Phuffng, ^MaiDlnh Tri, ^Trhn CdngLu^n

^Trung tdm Sdm va Du^c lieu Tp. HCM- Vi?n Du^c li$u
^Vifn Cdng ngh$ Hoa hpc, Viin Hdn ldm Khoa hpc vd Cdng ngh4 VietNam
(Nhgn bai ngay 14 thdng 3 nSm 2013)
Summary
Two Anthranoids Isolated from the Roots of Morinda officinalis How
Two anthraquinones were isolated from the dried roots of Morinda officinalis How collected at Dai Tu, Thai
Nguyen povince, and identified as 3,8-dihydrcQ^I,2-dimedKQ'andiraquinone and 2-hydro)^l3-dimedKHQ'anthraquincxie.
Their chemical structures were determined on the basis of spectroscopic analysis. This is the first report of 3,8dihydroxy-l,2-dimethoxyanthraquinone from the roots of Morinda officinalis and the nature as well.
Keywords: Morinda officinalis, Anthranoid, 3.8-dihydr(acy-l,2-dimethtxcyanthraquinone. 2-hydroxy
dimethoxyanthraquinone.
Cay ba kich {Morinda officinalis How^ la

ciy than thao,, s6ng ldu n ^ , thdn leo, tCr ldu

d3 dugrc su dimg lam thu6c chihi b^nh trong
dSn gian. Re phoi hay say kho dung lam
thuoc bo tri nao va tinh khi, chite xuat tinh
s6m, di mOng tinh, li?t duong, kinh nguy?t
chlmi ho^c bl kinh, phong th^p v^ huylt ap cao
[1]. Re ba kich dii^ anthraglucosid: Tectoquinon,
alizarin 1-methyl ether, lucidin-o>-metfaj4 ether,
l-hydroxy-3-fflefliylanthraquinon, l^ydroxy 2,3 - dimethyl - anthraquinon, rubiadin, mbiadin
- 1 - methyl ether. Cac iridoid glucosid gom:
Asperulosid, monotropeln, morindolid,
morofficinalosid, acid deacetyl a^^erulosidic,
add asperulosidic, acetat asperulosid. Cac sterol:
p-Sitostool, oxositosterol, 1 triterpen logi ursan;
Acid rotungenic monoterpenglucosid, 1 - borneol
-6-^>-p-D-apiosyl-p-glucosid. Lacton: (4R,5S)
-5-hydro:g' hexan-4-olid [2,3]. Cdc nghien cihi
gan day cho th4y cac hgp chdt dug'c tdch
chiet vd phdn l|ip tur re cdy ba kich cd tdc
dyng ch6ng viem, gidm dau [4], ch6ng lodng
xuong [5], tdng cudng sure chong chju va tac
dgng chong stress oxy h6a [6]. Do v^y, vi^c
Tgp chiDuac Uiu, tap 18, so 2/2013

nghien cihi thanh phan hoa hoc ciia re ba

kich gop phdn cimg c^p tu lieu cho cac
nghien cihi sdu hon ve tdc d\mg sinh hgc. Bdi
bdo nay de c^p den chilt tdch, xac djnh cau
tnic hai h^p chdt anthraquinon tii r ba kich
thu hdi a D^ Tfit, Thai Nguyen.
2. Vat ti^u va phmmg phdp nghiSn cuu
2.1. Vgt li^u nghiin cuu
Re ba kich (Radix Morindae) disgc thu hdi
cr D^ Tir, Thdi Nguyen vdo thang 3/2011.
MSU dd dugic dinh danh va cung cip boi Khoa
Tdi nguygn Dugc li^u, ViSn Dugrc li^u. Mau
dugc luu gitt a BO m6n Tdi nguySn-Dugrc
li^u, Tnmg tdm Sam vd Dugrc li6u Tp. HCM.
2.2. Phucmg phdp nghien cint
Ph6 NMR duofc do voi ky thudt 1-D vd 2D ('H-, '^C-, DEPT, HSQC, COSY, NOESY,
HMBC). M2U dugrc hoa tan trong CDCI3 v6i
chat chuan npi TMS; thuc hien tr6n mdy
AVANCE 500 BRUKER [500 MHz ('H) vd
125 MHz ('^C)] tii Ph6ng c4u true, D?u hgc
Khoa hoc T\r nhien Tp.HCM. Pho khoi do
tr8n may LC-MS t^i trung tdm nghiSn curu
hoa hgc cay thuoc, Khoa Dugrc, D^l hgc Y
Dupc Tp, HCM. Tin higu ghi nhgn theo so

khdi (m/z) va cuong dp tircmg doi (relative

intensity). Ph6 UV dugc do tren mdy HeWos
Y Thermo Spectronic (UNICAM-UK). M3U
dugc hda tan trong MeOH, ghi nh|n dinh hap
thu cvc d?i (X,, nm) va dp hap thu (Abs).
sic ley cpt dimg silica gel (c9 hat 40 - 63
(im, Merck). Slc ky 16p m6ng tren ban mdng
trdng sin silica gel 6OF254 (Merck).
2.3. Chiet xudt vet phdn lap
Bpt nguyen lieu (4,7 kg) duoc chilt ngam
ki^t bang c6n 45 % (ty If 1:10), thu dupc
djch chiet. Co giam ap dich chiet thu dupc
cao con (0,4 kg), hoa cao voi nuoc rdi ldc vdi
ether ddu hda (EP), cd gidm dp dich ether diu
thu dupc cao ether ddu (6 g). PhSn l|p cac
hpp chat til cao ether ddu (3 g) bdng SKC
silica gel voi h$ dung mdi gidi li (EP :
EtOAc) theo ty le tang ddn dp phan c\tc: (50 :
1) ^ (30 : 1) -> (10 : 1) -> (5 : 1) ^ (3 : 1)
-> (1 : 1). Thu dupc 10 phdn doan Ai-Aio.
Gdp hai phan dofin A7 vd Ag (0,473 g) va tiln
hdnh sdc ky cpt ldn 2 thu dupc 7 phdn dosm

Pi

D1-D7 voi h? dung mdi gidi li (CHCI3':

MejCO): 100 % ^ (100 : 1) ^ (50 : 1)
(20 : I) -> (10 : 1) ^ (5 : 1). Phan do?n Dj
(36,8 mg) dupc thvc hi?n sdc ky che hda tien
ban trang sdn silica gel triin khai vdi hf dung
mdi EP - EtOAc - HCOOH (75 : 25 : 1), sau
dd c?o ldy vdt chdt. Tach ra dupc hpp chit
PI, kdt tinh trong MeOH d djng hinh kim,
kiem tra vdd SKLM xudt hidn mpt vlt mdu
hong vdi thu6c thii NaOH 10 %/ aOH. Phdn
do?n Aio (0,206 g) thuc hifn sdc ky chl hda
tren ban tiang san silica gel trien khai vdi h$
dung mdi EP - EtOAc - HCOOH (75 : 25 :
1), sau do c^o lay vet chat. Tach ra dupc hpp
chat P2 d ^ g bpt vd dinh hinh, kilm tra vdi
SKLM xudt hien mdt vlt mau tim vdi thuoc
thii NaOH 10%/EtOH.
3. Ket qud va ban lu^n
Tir cao ether ddu hda ciia re cdy ba kich,
s i dyng sdc ky cpt silica gel pha thudng vdi
cdc hf dung mdi khdc nhau, chiing tdi phdn
l?p dupc hpp chdt PI vd P2.

P2

Hinh 1. clu trtic h6a hpc vi tucmg quan HMBC cua hffp chdt PI v4 P2

H91) chat PI
Hpp chdt PI ket tinh trong MeOH d?ng
tinh thi hinh kim, mau vang cam cho phdn
tag duong tinh voi thudc thii 1% FeCb/
EtOH cho thay PI cd thi la mdt hpp chdt
phenolic. Pho UV vdi dinh hdp thu cvc d?i
94

X = 217, 280 vd 407 nm. Ph6 khii lupng

(ESI - MS) ciia hpp chdt PI xuit hi$n pic ion
phan tir gid tn/z 299,40 [M-H]'tuong ting vdi
cdng thiic phdn tii CisHiaOj.
Cdc diJ lifu ph6 nghidm ciia PI cd SV
tuong d6ng vdi P2, trong dd PI od thdm tin
Tap chiDuac Uiu, tdp IS, s62/20a

hiu cua mpt nh6m -OH kilm noi [8H 12,97

(IH, s, 8-OH)], dhng thai vong A chi c6n ba
proton [6H 7,77 (IH, dd, J = 7,5 va 1,0 Hz,
H-5); 7,62 (IH, t, J = 7.5 Hz, H-6) vd 7,28
(IH, dd, y = 8,0 vd 1,0 Hz, H-7)]. Dir dodn
PI c6 khung cdn ban Id anthraquinon mang
bon nh6m thi (hai nh6m hydroxy va hai
nhom methoxy). Xet vdng A, tin hi$u (SH
12,97) tr6n pho 'H-NMR khdng dinh nh6m OH phdi gan vao C-8 khung anthraquinon.
Nhu v^y, carbon carbonyl (5c 181,6) ^ g voi
C-10, tin hifu carbon carbonyl con lai (5c
187,8) Id C-9.6 vdng B, proton H-4 [6H 7,71
(s)] cho tuong quan vcri carbon C-10 vd hai
carbon v6ng therm gin oxygen (5c 145,5 va
154,7), suy ra C-1 phdi Id carbon gin nhom
methoxy {5c 154,2). Them niia, carbon
methoxy 6c 61,6 ppm > 60 ppm, chiing to hai
vi tri ortho ciia carbon gin nhom methoxy c6
mang nhom thi. Vay, tin hi#u carbon (Sc
145,5) phu hpp vdi C-2 vd tin hi^u (5c 154,7)
Id C-3 (Bdng 1). Tir cac dfl: li?u phan tich pho
nghidm ket hpp voi cdc chi tilt tucmg tdc
xa dupc trinh bdy trong Hlnh 1, hpp chdt
PI dupc xdc djnh la 3,8-dihydroxy-l,2dimethoxyanthraquinon. Hgp chit ndy dupc
ting hpp vdo ndm 1986 bdi Cameron D. W.
vd Feutrill G. I. [7], nhung day Id ldn ddu
phat hi^n hpp chat nay trong thien nhien.
Hgp chat P2
Hpp chdt P2 d^ng bpt vo dinh hinh mdu
vdng cho phdn iing ducmg tinh v6i thuoc thur
1 % FeCb/EtOH cho thdy P2 c6 thi la mgt
hpp chat phenolic. Ph6 UV vcri dinh hap thu
cyc dgi ^ax = 280, 212, 363 nm. Pho khdi
lupng ESI-MS ciia hpp chat P2 xuit hign pic
ion phdn tCr gid m/z 285,42 [M+H]* vd 307,40
[M+Na]*, ling voi cong thiic phdn tfic
CifiHuOs.
Ph6 'H-NMR cua hpp chdt P2 xudt hin
tin hi^u c^ng hudng ciia mpt vong benzen the
1, 2 [6H 8,26 (IH, dd, J = 7,5 vd 1,5 Hz, HTgp chiDuac Uiu, tap 18, so 2/2013

8); 8,24 (IH, dd, J = 7,5 va 1,5 Hz, H-5);

7,76 (IH. dd, J = 7,5 vd 1.5 Hz, H-7) vd 7,73
(IH, dd, J = 7,0 vd 1,5 Hz, H-6)], mpt proton
dgng singlet [5H 7.71 (IH, s. H-4)] va hai
nhdm methoxy -OCH3 [5H 4,09 (3H, s, 3OCH3) va 4,04 (3H, s, I-OCH3)]. Phd '^CNMR kit hpp kj? thudt DEPT cho thay hpp
chit P2 cd mudi sdu carbon gom hai carbon
carbonyl [6c 182,4 (C-10) va 181,7 (C-9)],
mudi hai carbon vdng thom iing vdi hai vdng
benzen va hai carbon methoxy [5c 61,7 (1OCH3) vd 56,6 (3-OCH3)]. Trong mudi hai
carbon vdng therm cd ba carbon gin oxygen
[5c 151,3 (C-3); 147,2 (C-1) vd 144,9 (C-2)]
va nam carbon gin hydrogen [5c 133,9 (C7); 133,3 (C-6); 127,0 (C-8); 126,6 (C-5) vd
106,2 (C-4))]. Tir cdc dvt li$u phA nghiSm
trSn du doan P2 cd khung can ban la
anthraquinon mang bdn nhdm the (hai nhdm
methoxy va mpt nhom hydroxy). 6 vdng B,
proton dgng singlet H-4 (5H 7,71) cho tuong
quan vdi carbon carbonyl C-10 (5c 182,4) va
carbon vdng thom gin oxygen (6c 144,9)
trfin phd HMBC (Bang 1, Hinh 1), chimg td
tin higu carbon ndy Id C-2 ho|c C-3. Tuy
nhien, hai proton ciia nhdm methoxy khdng
cho tuong quan vdi carbon nay chumg td
carbon nay mang nhdm -OH. M^t khdc, tin
hi^u carbon methoxy 6c 61,7 ppm > 60 ppm,
cho thay hai vi tri ortho cua carbon gdn nhdm
methoxy nay cd mang nhdm the. Tin hiu
carbon cdn lgi 5c 56,6 ppm < 60 ppm, cho
thay it nhat mpt vj tri ortho cua carbon gin
nhdm methoxy ndy khdng mang nhdm thi.
Nhu vgy, nhdm methoxy (6c 61,7) se gin
vao C-1 (6c 147,2), nhdm methoxy (5c 56,6)
gin vdo C-3 (8c 151,3), tin hi^u carbon (6c
144,9) umg vdi C-2. Cdc chi tiet tucmg tac xa
dupc trinh bay trong Hinh 1. Tur cac dU li$u
phdn tich phd nghigm kit hpp vdi tdi ligu
tham khdo [8], P2 dupc xdc dinh Id 2hydroxy-l,3-dimethoxyanthraquinon.
95

Bang I. Dtt lilu ph6 'H-NMR v4 "C-NMR cua hgp chSt PI v4 P2

Vitri

I
2
3
4
4a
5
6
7
8
8a
9
9a
10
10a
1-OCH,
2-OCHj
3-OCH,
3-OH
8-OH

5c ppm
154,2
145,5
154,7
110,7
131,7
118,9
135,7
124,5
162,5
116,9
187,8
120,1
181,6
132,8
61,6
61,6

HrpchitPl
(CDCIj)
6ii ppm (mult, J in Hz)

7,71 (s)
7,77 (dd, 7,5 va 1,0 Hz)
7,62 (t, 7,5 Hz)
7,28 (dd, 8,0 va 1,0 Hz)

5c ppm
147,2
144,9
151,3
106,2
131,8
126,6
133,3
133,9
127,0

HrpchJtP2
(CDCb)
$H ppm (mult., y In Hz)

7,71 (s)
8,24 (dd, 7,5 v4 1,5 Hz)
7,73 (dd, 7,0 vi 1,5 Hz)
7,76 (dd, 7,5 v4 1,5 Hz)
8,26 (dd, 7,5 vi 1,5 Hz)

134,6
181.7

4,00 (s)
4,11 (s)

120,8
182,4
132,7
617

4,04 (s)

56,6

4,09 (s)

6,46 (s)
12,97 (s)

4. Ketlu^n
_
Tir cao cin 45 % rl ba kich, sft dung ky
thuat sdc ky cdt, sdc ky chl hda kit hpp cac
ky thujt phd, hai hpp chat anthraquinon dd
dupc phdn lip yd xac dinh ciu tnic la 3,8-

dihydroxy-1,2-dimethoxyanthraquinon (PI)
vd 2-hydioxy-l,3-dimethoxyanthiaquinon (P2).
Trong do, cd mdt chit anthraquion dupc xem
Id hpp chdt mdi lan ddu tidn dupc tim thiy
trong tv nhien vd dupc phan lap tir rl ba kich.

Tdi lifu tham khdo

I. Do Tit L?i (2009), WiSng cdy thudc vj tiiudc VietNam. NXB Y Hflc, 303-304.2. Vifn Dir(n: li|u (2004), Oy
thudc va aqng vft lam thudc a Viet Nam. NXB Khoa hpc KJ thu$t, tp I, 101-106. 3. Yoshikawa M.,
Yamaguchl S., Nishisaka H., Yanahara J. and Murakami N. (1995), Chemical constituents of Chinese nature
medicine, morindae radix, the dried roots of iviorinda officinalis How: Structutes of morindolide and
morofflcinaloside. Chem. Pharm. Bull., 43 (9). 1462-1465. 4. Choi J., Lee K. T., Choi M. Y., Nam J. H., Jung H.
J., Park S. K., Park H. J. (2005), Antinociceptive Anti-inflammatory effect of monotropein isolated from the root
ofMorinda officinalis. BioL Pharm. Bull.. 28(10), 1915-1918.5. Rong Z. D., Yu W., Jing Z., Quo Z. J., Ui L
Qmg B. J. (2010), Morinda officinalis How enhances exercise endurance ai]d possesses protective effects against
oxidative sfress of the rats after exercise. African Journal of Microbiology Research, 4(15), 1609-1615.6. Wu Y
B., Zheng C. J., Qin L. P., Sun L. N., Han T., Jiao L Zhang Q. Y., Wu J. Z. (2009), Antiosteoporotic activity of
anthraquinones from Morinda officinalis on osteoblasts and osteoclasts, Molecules, 14, 573-583. 7. Cameron D.
W., Feutrill G. I., Gamble G. B., Stavrakis J. (1986), Synthesis of specifically 0-alkylated anthraquinones by
cycloaddition. Tetrahedron Letters. 27(41), 4999 - 5002. 8. Banthorpe D. V. and White J. J. (1995), Novel an
anthraquinone from undifferentiated cell cultures ot Galium verum. Phytochemistry. 38(1), 107-1II.
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Tap chiDuac Uiu, tdp 18, sU2/2013