DAI HOC
QUOC
GIA HA NOI
TRUONG DAI HOC KHOA HOC TU NHIEN
DE TAI NGHIEN
CWU
KHOA HOC
TONG
HQP
VA
CHUYEN
HOA
•
MOT SO DAN XUAT
CUA
a-D-GLUCOZa
VA
a-D-GLUCOZAMIN
Mas6:
QT-05-16
CHU
TRI DE
TAI: PGS.TS. NGUYEN DINH THANH
CAN
BO
THAM GIA: 1. Th.S. Pham
H6ng
Lan
2.
Cac sinh vien phong
THHC-l

2.1.4 Mot
so
tinh chat cua glucozylamin 2
2.2 Tong quan ve glycozyl isothioxianat 5
2.2.1 Giai thieu ve glucozyl isothioxianat 5
2.2.2
Phuang
phap tong hgp glucozyl isoxianat/isothioxianat 5
2.3.3 Tinh chat hoa hoc
ciia
glucozyl isoxinat/isothioxianat 7
B
Phan
thuc nghiem 9
2.3 Tong hgp cac 2-axetamido-2-deoxi-D-glucopiranozylamin (GlcNAcamin)) tir
N-axetyl-
p-D-glucozamin
9
2.3 Tong hgp
4,6-0-etyliden-D-glucopiranozylamin
tij
4,6-0-etyliden-D-gIucoza
(EtGIcamin) 12
2.4 Tong hgp 3-glucozylaminoisothiazolo[3,4-d]pirimidin
(GAIP)
tir glucoza 14
C Ket qua va ban luan 18
2.5 Tong hgp cac glucopiranozylamin (GlcNAcamin)
tirN-axetyl-P-D-glucozamin
18

TAT
Me
Metyl
Et
Etyl
Bu-n
n-Butyl
Ac Axetyl
EtGlc
4,6-0-Etyliden-D-glucoza
ADGLCNAc
N-axetyl-a-D-glucozamin
BDGLCNAc N-axetyl-P-D-glucozamin
GlcNAcamin 2-Axetamido-2-deoxi-D-glucopiranozylamin
EtGIcamin
4,6-0-Etyliden-D-glucopiranozylamin
Galamin Galactopyranosylamin
GAIPl
2,3,4,6-tetra-0-axetylglucopiranozylaminoisothiazolo[3,4-d]pirimidin
1
MODAU
Nhu da biet, cacbohidrat thamgia vao thanh phin
ciia
rat nhieu loai hgp chat hoa
hoc trong thien nhien, tir cac duang dan co mat trong nhieu loai hoa qua nhu fructoza,
cac disaccarit nhu saccaroza (duong
mia)
den cac polysaccarit nhu
xenlulo,
tinh

J^J
(co ten hoa hgc la
2',3'-dideoxy-2',3'-didehidrothimidin),
deu la cac N-
glycozit
ciia
amin di vong chua nita la pirimidin va monosaccarit la dan xuat azit
ciia
ribofuranoza
[6-11].
Nhin chung, hoa hoc cacbohidrat chua dugc nhieu nha khoa
hpc
trong nuac
nghien cim. Trong mpt vai nam gan day da xuat hien mpt so cong trinh nghien cim trong
ITnh
vuc nay
ciia
cac tac gia Viet nam (xem tai lieu dan ra a duoi), song hau het la a
ITnh
vuc oligosaccarit hay polisaccarit, ma
chii
yeu la chi a mirc dp bien tinh cac polime nay.
Vi vay de tai
ciia
chiing toi co muc tieu va npi dung nhu sau:
+ Muc tieu:
1.
Tong hgp mpt so hgp chat glycozylamin c6 chira nhan di vong
1,3-thiazol
va

thiazol.
2.
Nghien
ciai
thuc hien cac phan img chuyen hoa tren ca sa cac hgp chit nhan
dugc a tren.
3.
Nghien cim moi quan he cau
triic-tinh
chat hay cau
triic-hoat
tinh bing cac tinh
toan
hoa lugng tir
(aft
initio,
AMI,
PM3, )hay
ca
hpc phan
tir
(MM+, AMBER, ).
4.
Cau
true
cua cac hgp chat nhan dugc se dugc xac nhan bang cac phuang phap
vat ly hien dai (pho hong ngoai, pho cong huang tir hat nhan proton va
cacbon-13
va pho
kh6i

/ (khong goi
Id
anilin
^D-glucopiranozit.
2.L2
Tdc dung sinh
hgc
cda glycozylamin
Co mpt so rat 1cm cac hgp chat cacbonhydrat co chira nita. Trong do co
nhi6u
hgp
chat
CO
nhieu cong dung dac biet. Chung c6 nhieu hoat tinh sinh hpc quan trpng va
glucozylamin cung la mpt trong cacbohidrat c6 chira nita co nhieu hoat tinh sinh hpc
quan trpng.
2.1.3
Phitomgphdp
tong
hpp
glucozylamin
Phuang phap thuong hay sir dung de dieu che glucozylamin la sir dung phan img
ngung tu giira amin va duong khir trong dung moi metanol hoac etanol soi, c6 chira 10%
lugng
H2O
va co mpt lugng nho axit lam
xiic
tac. San pham tach ra duai dang tinh
th6
sau khi cho bay hoi dung moi va lam lanh.

cin phan biet cac
tinh chat von co
ciia
chung nhu tinh amin. tinh chat dac trung
ciia
duong va
nhijns
tinh
chat dac
thii
gay nen boi su tuong tac giua cac nhom
hidroxi,
amin, cac nhom
thi
1.
Su ddo quay
Sir
dao quay cua cac glucozylamin co dugc la do ton tai mot can bang trong do
xay ra su chuyen dich cac anome thong qua cac hgp chat trung gian khong vong
bazo
Schiff:
CgHsNH
CH
H
C—OH
__^ CgHgN^CH
H
C—OH
HC—NHCgHs
H

—I
HA
Su chuyen mpt cap electron tir nguyen tir nito
ciia
nhom amoni dan den su hinh
thanh ion imonium. Tir do dan den su chuyen tir dang vong den dang khong vong va
ngugc lai. Giira chiing co mpt can bang dugc hinh thanh.
3.
Sir
ddo quay trong moi
trudng
baza
Co che xav ra nhu sau:
HCNH.
HCO
HCNi-^
+ B
HC0-
HG=NH
BH.NCH
+ HB
^ ^
HCO
I
HCO
HjNCH
(1)
HCO
I
-i-B

I
H
+
I
HO^G
—
C-
+
•OH
SP
Nguoi ta thay rang
toe
dp thuy phan glucozylamin phu thupc vao pH cua dung
dich va chung dat
cue
dai trong moi truang axit yeu. Do la do qua trinh thuy phan can ca
xuc tac axit va xuc tac bazo.
5. Axetyl hod glucozylamin
Phuong phap hay dugc sir dung de axetyl hoa glucozylamin
la
cho glucozylamin
phan img voi lugng du anhidrit axetic trong piridin
a
O^C
trong thoi gian tir 2 gio den hai
ngay. Dung dich sau phan ung dugc rot vao trong nuoc da. Sau vai gio chat ran dugc
gom lai va ket tinh lai bang etanol.
Duoi dieu kien khac nghiet hon thi nguyen tir hidro
ciia
nito ciing bi thay the. San

co
che xuc tac bang axit.
H NRR'
H-
HO-
H-
H-
^^O
•H
^
•OH
+
H
R—NH-R'
H-
H-
HO-
H-
H-
CH2OH
HC=N-R
OH
•H
OH
i
CH2OH
HC=NH-R
HC-NRR'
OH
•H

R'
HO-
H
H-
O
-H
-OH
OH
CH2OH
R—NH-R'
I
H2C
HO
HO
H-hOH
H
C=OH
I
•NH-R'
I
H2C
H*
C^O
HO-
HO-
H-
H-
-H
-OH
-OH

P-xiclodextrin
co cac tinh chat dugc ly cao [42, 44,
45].
Cac isothioxianat de dang tham gia cac phan ung cong hgp va cong hgp-dong vong,
cac phan img voi cac nucleophinl khac nhau chi ra
'dac
trung electrophin manh cua
nhom -NCS. Su day electron manh cua nguyen tir cacbon trong nhom -NCS dong vai tro
quan trong trong nhimg phan img nay.
R N=C^S
Cac nucleophin gan voi nguyen tir hidro de tach ra va co kha nang proton hoa
nguyen tir nito deu co the phan img voi isothioxianat, trong khi do phan am dien se lien
ket voi nguyen tir cacbon
ciia
nhom -NCS:
R
N^C=S
+ HX
^ R NH-C
X
:S:
2.2.2
Phuorng
phap tong
hprp
glucozyl isoxianat/isothioxianat
Lan dau tien Fischer da tong hgp dan xuat isothioxianat
ciia
monosaccarit bans
each

dong phan hoa nhiet hgp chat thioxianat tuong ung nhan dugc tir
2,3,4,6-tetra-O-axetyl-
a-D-glucopiranozyl
bromua va kali thioxianat trong axeton:
N=c=s
OAc,
Dang
•S-C=N
H
^""H
chu y la
1,3,4,6-tetra-0-axetyl-2-amino-2-deoxy-a-D-glucopiranoza
hidrobromua phan img voi bac thioxianat cho
2-axetamido-3,4,6-tri-0-axetyl-2-deoxy-P-
D-glucopiranozyl
isothioxianat, trong phan img nay xay ra su di chuyen
0-axetyl->N-
axetyl:
H
^^^'
H
OAc
H
^OAc
N=C=X
H
NHAc
AgXCNAcO-VVir^
- AcoOynV^H
H \

H2OH
NHsBr ^
CXQz/
OH"^
0
NCX
CH2CI2
• — - I RO
Khi sir dung muoi kim loai kiem nguoi ta thuong diing cac xuc tac chuyen pha
n6u
khong, san pham cua phan ung chi la cac dan xuat xianat hay thioxianat thong thuong. 6
day, xuc tac chuyen pha c6 vai tro trong viec dong phan hoa dan xuat xianat hay
thioxianat thanh dan xuat isoxianat va isothioxianat. Cac xuc tac chuyen pha
thudng
dimg
la diankyl ete cua polietilen glycol, cac ete vong, cac muoi tetraankyl halogenua bac 4.
Cac muoi kim loai kiem thuong dugc sir dung la natri thioxianat, kali thioxianat va amoni
thioxianat. Hieu suat phan ung kha cao, tir 70-80%.
•OAc
OAc
N=C=X
2.3.3 Tinh chdt hod hpc cda glucozyl isoxinat/isothioxianat
1.
Phdn
irng
vai amoniac vd amin. Su tao thanh cdc ddn xuat ureit vd thioureit
Tuong tu nhu cac
aryl
isoxianat va thioisoxianat, cac glucozyl isoxianat va
isothioxianat khi tac dung voi cac amin bac 1 (amin beo, tham hay di vong ) trong cac

NHs^.a'
Benzen khan Ac
»-
NH-C-NH-CH
II
\
X
COOMe
3.
Phdn irns amit
l-(2,3,4-Tri-(9-axyl-y^-D-glucopiranozyl)-3-phenaxyl-ure/thioure
ciing dugc
di^u
ch^
til phenaxylamin
hidroclorua trong moi truong khi tro:
NCX
+Ph-CONH2.HCl
dung dich
NaHCOj
R
*-
khucfy 6 dki
>fH-C-NH-COPh
11
X
4. Phdn
tens
vai aminoaxeton hidroclorua
Phan ung dugc tien hanh trong moi truang khi tro voi dan xuat cua glucopiranozyl

isothioxianat cho cac thioure tuong ung. Su vong hoa kem theo desunfua hoa cua cac
thioure nay bing
each
diing metyl iodua trong THE cho cac glycozylaminobenzimidazol
va N-glycozyl-3-deazapurin tuong img:
8
HjN^
N N
^NH2 N
N
"^NHR
H
R
=
2,3,4,6-tetra-O-axetyl-p-D-glucopiranozyi
B Phan
thyc
nghiem
-
Diem nong chay dugc
do
tren
may HMK
70/3159.
Pho
hong ngoai dugcghi tren
may
FTIR
Magna
760

Cau
true,
Vien
Hoa hpc,
Vien
Khoa
hpc va
Cong nghe Viet
nam); . Sac ki lop
mong dugc thuc hien tren
ban
mong
trang
san
DC
60
F254
(Merck).
2.3 Tong
hpp cdc
2-axetamido-2-deoxi-D-glucopiranozylamin (GlcNAcamin)
)
tirN-
axetyl-P-D'glucozamin
2.3.1 Tong
hap
2-axetamidO'2-deoxi-l3'D'glucopiranoza
(N-axetyl-P-D-glucozamin)[13]
Them timg
mau nho

hgp
trong
4-5
phut
va
Ipc
qua
pheu
Ipc
Buchner haygiay
Ipcgap.
Neu
cac dilu kien tren dugc
dap img thi
khong quan
sat
thay tinh
the
ciiaglucozamin
tu do.
N8u
khong
loc
ngay
hon hgp
phan
img
ngay
sau khi ket
thuc phan

phai bang
1,2-1,5
duong lugng,
su
N-axetyl
hoa
xay
ra mpt
each
chpn
ipc va
phan
img
nhanh chong
ket
thiic,
bai vay
lugng
du cua tac
nhan
axyl
hoa
phan
img
khong
anh
huong. Trong
qua
trinh
ket

thuc viec
lam
lanh va giu dung dich trong khoang
12gia 6 -25°C
va mot vai gio o
0°C.
Nghien nho can
than ket
tiia
tinh the tao thanh bang thia,
Ipc
tren
phlu
Ipc Buchner va rira bang 100 ml
metanol. De kho san phim tren
phlu Ipc
ngoai khong khi, sau do trong binh hut am chan
khong tren
P2O5.
Hieu suit san phim dat
88,25g
(78,3%),
Dnc
204-205°C,
[a]D^'
+75->+42°
(c 2, nuoc). Theo tai lieu tham khao [13]:
Dnc203-205°C,
[a]D^'+75^+42°
(c

2.3.2 Tong hop cdc 2-axetamido-2-deoxi-D-glucopiranozylamin (GlcNAcamin)
tir
N-
axetyl-p-D'glucozam
in
OH +
NH-
A
NHGlcNAc
NHAc
R=H (I), CH3 (II). COOMe
(III).
COOEt (IV)
NHGlcNAc
Sado
2. Tdng hap
2-axetamido-2-deoxi-D-glucopiranozylamin
(GlcNAcamin) tu N-
axetyl-p-D-glucozamin.
Qui trinh tong hap chung: Cho (0,005mol)
2-aminobenzo-1,3-thiazol
hay 2-
amino-1,3-thiazol
the khac nhau va
l,12g
(0,005mol)
N-a.xetyUP-D-glucozamin
vao
trong 25ml etanol
96''

2
3
4
5
Hgp chat
GlcNAcamin-1,
R=H
GlcNAcamin-2,
R=CH3
GlcNAcamin-3,
R=COOMe
GIcNAcamin-4,
R=COOEt
GlcNAcamin-5
Dnc,
T
228-230
186-188
220-222
236-238
218-220
Hieu
suat,%
50
49
67
58
62
Pho hong ngoai, cm''
VOH

Tong:
hap
N-(benzo-l,3-thiazol-2-yl)-2-axetamido-2-deoxi-a-D-glucopiranozylamin
(GlcNAcamin-1)
Tir
0,75g
(0,005mol)
2-aminobenzo-1,3-thiazol
va
1,12g
(0,005mol) N-axetyl-P-
D-glucozamin. Hieu suat
0,83g
(50%). San pham ket tinh dang tinh the hinh kim, mau
trang, nhiet dp nong chay
228°C.
Pho hong ngoai:
VoH=3455cm'\
VNH=3326cm'',
vc=o=
1628cm"',
5NH=
1549cm*'.
2) Tong hap
N-(6-met\dbenzo-L3-thiazol-2-yl)-2'axetamido-2-deoxi-B-D-glucopiranozyl-
amin
(GlcNAcamin-2)
Tir
0,82g
(0,005mol)

5NHl562cm'',
Vc=0(este)
1698cm''.
4)
T6n2
hap
N-(6-cacboetoxibenzo-L3-thiazol-2-vl)-2-axetamido-2-deoxi-B-D-gluco-
piranozylamin
(GlcNAcamin-4)
Tir
1,11
g
(0,005mol) etyl
2-aminobenzo-1,3-thiazol-6-cacboxylat
va
1.12g
11
(0,005mol)
N-axetyl-P-D-glucozamin.
Hieu suit
l,08g
(58%). San phim
kit
tinh dang
tinh the hmh kim, mau vang, nhiet dp nong chay
236-238°C.
Ph5
hdng ngoai:
VoH=3365cm'',
VNH=3299cm'',

4,6-O-etyliden-D-glucopiranozylamin
tit
4,6-0-etyliden-D-glucozo^
(EtGIcamin)
2.3.1
Tong hap
4,6-O-etyliden-D-glucoza
(Sa do 3)
Cho tir tir 0,2ml axit sunfuric dac vao 27ml parandehit, roi rot hon hgp nay vao
binh cau chua 36g
D-glucozo.
Sau do lac manh trong khoang 30 phut de hon hgp tro
thanh trang thai nira ran, de
6
nhiet dp phong trong 3 ngay. Khuay hon hgp trong 120ml
etanol tuyet doi, dieu chinh pH dung dich 6,5-7,0 bang dung dich
Na2C03.
Dun nong cho
tan het chat ran (co the diing than hoat tinh de hap phu chat ban). Dung dich de qua dem
tao tinh
thi.
Hieu suit 14-16g (70-80%). Nhiet dp nong chay
179°C-18rC.
Theo tai lieu
[14,15]:
179°C-18rC.
OH
HO^r
V
parandehit/HCI

phan img
6
nhiet dp phong, san pham se dugc tach ra. Lpc hut, say kho. Tien hanh ket
tinh lai san phim trong etanol 96°. Sau day la cac trucmg hgp cu the (xem Sa dd 4 vd
Bdng
2).
I)
Tdn2
hap
4.6-O-etvliden-N-(4-phenvl-l,3-thiazol-2-vl}-0~D-slucopvzanoz\'lamin
(EtGIcamin-1}
Tir 0,82g
4-phenyl-2-amino-1,3-thiazol
va
l,03g
(0,005mol)
4,6-O-etyliden-D-
12
glucoza Hieu suit 30%. Nhiet dp nong chay
180-182°C.
Ph6 hdng ngoai
VOH=
3365
cm"',
visjH=3220cm'*.
2) Tons hap
4,6-O-etyliden-Nf4-(p-metvlphenyl)-l,3-thiazol-2-ylJ-0-D-slucopyzanozyl-
amin
(EtGlcamin-2)
Tir

N-(benzothiazol-2-yl)-4,6-0-etyliden-p-D-glucopyranozylamin
SoTT
1
2
3
4
5
6
Hgp chat
EtGlcamin-1,
R,=H
EtGlcamin-2,
Ri=CH3
EtGlcamin-3,
R]=C1
EtGlcamin-4,
R2=H
EtGlcamin-5,
R2=CH3
EtGlcamin-6,
R2=C00Et
Dnc,
°C
180-182
136-138
170-172
193-194
239-240
228-230
Hieu

3) Tons hap
4,6-O-etyliden-N-f(4-(p-clovhenyl)-l,3-thiazol-2-yll-0-D-glucopyzanozvl-
amin
(EtGlcamin-3)
Tir
l,06g
2-amino-4-(p-clophenyl)-l,3-thiazol
va l,03g (0,005mol) 4,6-0-
etyliden-D-glucozo.
Hieu suit 35%. Nhiet dp nong chay
170-172°C.
Ph6
hdng ngoai
voH=3365cm"',
VNH=3220cm*'.
4) Tong hap
4,6-O-etyliden-N-(benzo-1.3-thiazol-2-yl)-0-D-glucopyranozylamin
(EtGlcamin-4)
Tir 0,75g
2-aminobenzo-1,3-thiazol
va l,03g (0,005mol)
4,6-0-etyliden-D-
glucozo.
Hieu suat 38%. Nhiet dp nong chay
193-194°C.
Pho hong ngoai
VOH=3460
cm'',
VNH=3275cm"'.
5)

cm"'.
2.4 Tdng hap 3'glucozylaminoisothiazolo[3y4-d]pirimidin (GAIP)
tieglucozff
2.4.1
Tong hap
2,3.4,6-tetra-O-axetyl-0-D-glucopiranozvl
isothioxianat (Sa do 5)
1) Tdng hap
2.3,4,6-tetra-O-axetyl-a-D-glucopiranozyl
bromua
[16,17]
Nho timg gipt 2,4ml axit pecloric 54% vao 40ml
anhidrh
axetic trong binh cau 3
c6
250ml
CO
lip may khuay, pheu nho gipt, nhiet ke va dugc lam lanh bang nuoc da. Sau
do dung dich dugc lam am den nhiet dp phong,
lOg
a-D-glucozo
monohidrat dugc them
tir tir vao hon hgp dang khuay voi
toe
dp sao cho nhiet dp phan img nam trong khoang 30
-
40*^C
trong 30 phut. Photpho do (3g) dugc them vao sau khi lam lanh hon hgp phan img
xudng
20°C

do 5. Tdng hgp
2,3,4,6-tetra-O-axetyl-p-D-glucopiranozyl
isothioxianat
tir
D-
glucoza.
Clorofom (30ml) dugc them vao, hdn hgp dugc lpc qua phlu lpc xdp. Binh phan
ung va pheu lpc dugc rira bang 10ml clorofom. Dich lpc dugc rot vao 80ml nude da dugc
chiira trong pheu chiet
250ml.
Sau khi rua, ldp clorofom dugc chiet tiep vao pheu chiet
250ml khac cd chua 30ml
nude
lanh. Qua trinh dugc lap lai bang
each
them
lOmI
clorofom vao dung dich nuoc ban dau va hgp nhat cac dich chiet clorofom lai. Sau khi
lac manh, ldp clorofom dugc rot vao 75ml natri hidrocacbonat bao hoa trong cdc 500ml
va khuay manh. Hdn hgp dugc chuyen vao pheu chiet 250ml, rdi them mpt it clorofom va
lac manh. Chiet lay ldp clorofom dugc khuay vdi 5g silic dioxit mdi nung. Hdn hgp dugc
lpc,
dem cd dudi ap suat thap de loai bd hoan toan dung mdi, thu dugc khdi ran tinh the.
Nghien chat ran trong cdc vdi 30ml hdn hgp ete dau hoa va ete (2:1 v/v) thu dugc cac
tinh the min mau trang xdp, lpc tinh the va rira chat ran bang mdt lugng ete lanh,
tetra-0-
axetyl-a-D-glucopiranozylbromua
dugc lam khd dudi ap suat thap tren NaOH ran. Hieu
suit 14g (58%), nhiet do ndng chay
88°C,

1232cm"';
VN^=S
2095 cm"'.
2.4.2
Tdng
hap
3-glucozvlaminoisothiazolo[3.4-d]pirimidin
(GAIP)
Phuang phdp chung tong hap cdc hap chdt cua
3'glucozylamino-
isothiazolo[3,4-d]pirimidin:
Hdn hgp
ciia
0,39g (0,001
moi)
2,3,4,6-tetra-O-axetyl-P-D-
glucopiranozyl isothioxianat va
0,001
moi
6-aminouraxin (hoac
6-amino-2-thiouraxin)
trong
10ml
xilen khan dugc dun hdi luu each dau trong thdi gian 14 gid, sau dd lam bay
hoi dung mdi phan img d nhiet dp phdng hay d dudi ap suat giam. Phan can dugc lpc va
kit
tinh lai trong dung mdi toluen. Sau day la cac trudng hgp cu the (xem Sa do 6 vd
Bdng 3a vd 3b).
15
N=C=S >r

thi
3-glucozylaminoisothiazolo[3,4-
d]pirimidin-4,6-dion, hieu suit
43%,
kit
tinh
lai
trong toluen, nhiet dp ndng chay
84^C.
Phd hdng ngoai:
Vc=o(este)
=1742cm"';
Vc-o-C(esie)=
1226cm*' va
V^.H
=3463cm"'.
2) Tdng hap
3-glucozylaminoisothiazolo[3.4-dlpirimidin
-7-phenyl-4,6-dion (GAIP-2)
Tir
0,39g
(0,001
moi)
2,3,4,6-tetra-O-axetyl-a-D-glucopiranozyl
isothioxianat va
0,2g
6-amino-l-phenyluracil
thu dugc
0,25g
tinh

54
52
43
53
56
Bdng
3a.
Cdc ddn xudt cua
3-glucozylaminoisothiazolo[3,4-d]pirimidin
Ki hieu Nhdm the
GAIPl
R:=H;
X=0;
R2=H
GAIP2
Ri=H;
X-0;
Rz^CeHs
GAIP3
Ri=H;
X=0;
R2=o-CH3C6H4
GAIP4
Ri=H;
X=0;
R2=p-C2H50C6H4
GALP5
Ri=H;
X=0;
R2=p-BrC6H4

kit
tinh lai trong toluen. nhiet dp ndng chay
100°C.
Phd hdng ngoai:
vc=o
(este,
=1743cm
16
-1
Vc-o-c (esicr
1245cm"';
VN-H
=3305 va 3494cm''.
4) Tdng hap
3-2lucozylaminoisothiazolo[3.4-dl
pirimidin
-7-(p-etoxiphenyl)-4,6-dion
{GAIP-4)
Tir
0,39g
(0,001
moi)
2,3,4,6-tetra-O-axetyl-a-D-glucopiranozyl
isothioxianat va
0,28g
(0,001mol)
6-aniino-l-p-brom-phenyluracil
thu dugc
0,35g
tinh

vco-c (este)
1248;
VN-H
3450
Vc=o
1743;
vco-c (este)
1225;
VN.H
3494
Vc=o
1753;
Vc^.c(este)
1245;
VN.H3499
GAIPl
GAIP2
GAIP3
GAIP4
GAIP5
GAIP6
GAIP7
GAIP8
vc=o
A/-'-J,
vc^.c(este)
i^^^,
v^-H-J^^^
vco
1744;

1040;
vc-o-c (este)
1229;
V^.H
3459
Vc=o
1744;
vc=s
1040;
vco-c (este)
1240;
VN-H
3487
5) Tdng hap
3-glucozylaminoisothiazolo[3A-d]pirimidin
-7-(p-bromphenyl)-4,6-dion
(GAIP-5)
Tir
0,39g
(0,001
moi)
2,3,4,6-tetra-(9-axetyl-a-D-glucopiranozyl
isothioxianat va
0,25g
(0,001 moi)
6-amino-l-/?-etoxiphenyluracil
thu dugc
0,34g
tinh the 3-
glucozylaminoisothiazolo[3,4-d]pirimidin-7-(p-bromphenyl)-4,6-dion, hieu suat 54%,

3-
glucozylaminoisothiazolo[3,4-d]pirimidin-4-on-6-thion, hieu suat 43%, ket tinh lai trong
toluen, nhiet dp ndng chay
88°C.
Phd hdng ngoai:
Vc=o (este)
=1744cm"';
Vc-o-c(este)=
1248cm"';
vc=s
=1038cm"' va
VN-H
=3490cm''.
7)
Tdn2
hap
3-2lucozylaminoisothiazolo[3,4-dlpirimidin-7-phenyl-4-on-6-thion
(GAIP-
71
Tir
0,39g
(0,001
moi)
2,3,4,6-tetra-(9-axet>'l-a-D-glucopiranozyl
isothioxianat va
17
DAI HOC QUOC GlA
HA rjOl
TRUNG TAT/ THONG TIN THU
VlEhJ

6-amino-l,3-diphenylthiouracil
thu dugc 0,38g tinh
thi
3-
glucozylaminoisothiazolo[3,4-d]pirimidin-5,7-diphenyl-4-on-6-thion,
hieu suit 56%),
kit
tinh lai trong toluen, nhiet dp ndng chay
108°C.
Phd hdng ngoai:
vc=o (este)
=1744cm"';
Vc-o-c
(cste)='1241cm'';
vc=s=1038cm"'
va
VN.H=3487cm"'.
C Ket qua va ban luan
2.5 Tong hop cac glucopiranozylamin (GlcNAcamin)
tir
N-axetyl-P-D-glucozamin
Bang
each
cho dan xuat
2-aminothiazoI
va
2-aminobenzothiazol
vdi N-axetyl-P-
D-glucozamin trong etanol 96%, thdi gian phan ung trung binh tir 30-50h se thu dugc
cac san pham glucozylamin vdi hieu suat tucmg ddi cao (50 - 60%) (xem Bdng

5NH d 1562-1549 cm"'. Ngoai ra trong phd cdn xuat hien mdt sd bang sdng hap thu dac
tnmg cho dao ddng hoa tri cua lien ket
C=C
trong nhan di vdng thom d vimg
1549-1528
va 1465-1464 cm'' (xem bdng 1).
Trong phd 'H-CHTN
ciia
cac glucozylamin ndi tren, cd hai vimg tin hieu cdng
hudng, tuang img vdi hai loai proton trong phan tir: cac proton trong nhan thom benzen
va nhan dj vdng thiazol cd cac tin hieu cdng hudng nam trong viing 7,112-8,543 ppm;
cac proton cua hgp phan cacbohidrat cd tin hieu cdng hudng d viing <5 ppm: cac nhdm
OH vdi dp chuyen dich hod hpc d 4,546-5,347 ppm, cac proton no trong vdng piranozo
cd dp chuyen dich hoa hpc nam trong viing 3,224-4,975 ppm. Proton
ciia
lien ket amit
(trong nhdm N-axetyl
ciia NTI-CO-CH3)
cd dp chuyen dich hoa hpc nam trong viing
18
5,768-6,435 ppm. Nhdm amino bac 2 cua glucozylamin cd tin hieu d dang duplet d
8,344-8,534 ppm. Ngoai ra trong phd CHTN cdn cd cac tin hieu dac trung cho cac nhdm
proton cua cac nhdm metyl va etyl trong timg phan tu rieng biet.
2.6 Tdng hgrp
4,6-O-etyliden-D-glucopiranozylamin
(EtGIcamin)
tu*
4,6-O-etyliden-
D-glucoza
Cac

N-benzothiazolyl.
Su thay ddi ve dp dao
quay xac dinh ddi voi
P-D-glucopiranozylamin
la rat nhd, dieu dd chung td toan bd san
pham thu dugc d dudi dang P-anome.
Phan img dugc tien hanh trong dung mdi la etanol tuyet ddi, khi dun ndng, khi dd
ca amin va dan xuat
4,6-0-etylidenglucopiranoza
deu tan tdt trong dung mdi nay.
Xuc tac dimg cho phan img nay la axit axetic bang, tao mdi trudng axit yeu vi neu
sir dung axit manh hon nhu axit
HCl,
axit oxalic, thi cac glucozylamin tao thanh cd the
tham gia vao phan ung chuyen vi Amadori, tao thanh cac
xetozo.
Cau
true
cua cac
IN( — .glucozylamin
dugc xac nhan bang each ghi phd hdng
ngoai, phd 'H- va
'^C-NMR
va phd khdi lugng. Trong phd hdng ngoai
ciia
cac N-
(benzothiazol-2'-yl)-P-D-glucopiranoz>'lamin
va
N-(4'-phenylthiazol-2'-yl)-P-D-gIuco-
piranozylamin cd cac bang sdng hap thu dac trung cho cac nhdm the cd mat trong phan

trong phd CHTN cdn cd cac tin hieu dac tnmg cho cac nhdm proton cua cac nhdm metyl
va etyl trong timg phan tir rieng biet (5
1.07-2,51
ppm).
2.7 Tdng hop cac hop chat cua 3-glucozylamino- isothiazo!o[3,4-dl pirimidin
Trong phan img
ciia
2,3,4,6-0-tetra-0-axet>'lglucopiranozyI
isothioxianat vdi 6-
aminouraxin va 6-amino-2-thiouraxin the, nhdm isothioxianat tan cdng vao C-4
ciia
vdng
pirimidin tao thanh san pham trung gian va sau dd xay ra
sir
vdng hoa npi phan tir giira
nhdm
>C=S
va
NH2
cho vdng isothiazol (xem Sa do 6)
19
Cac
din
xuit 3-glucozylamino-isothiazolo[3,4-d]pirimidin da tdng hgp dugc trinh
bay trong bang 1. De thuc hien cac tdng hgp nay, hdn hgp phan ung gdm
tetra-0-axetyl-
yff-D-glucopiranozyl
isothioxianat va cac dan xuat
ciia
6-aminouraxinythiouraxin

m/z
169. Ngoai ra cdn
xay ra
sir
tach ion gdc
S"^
tao thanh ion manh m/z 482, tuy nhien day chi la chieu hudng
phan cat vdi xac suat thap hon hai chieu hudmg phan cat ke tren. Ion manh m/z 169 phan
manh tucmg tu nhu d axit bacbituric, d day xay ra su phan cat lien tiep hai phan tir
HCNO dan tdi
sir
tao thanh ion manh m/z 83
{xem
Sa dd 7).
Ion manh cua phan gdc monosaccarit vdi sd khdi m/z
331
tiep tuc bi phan manh
cho cac ion manh m/z 157, 242 va
271.
Ion manh m/z bi phan cat mach cacbon kem theo
su tach phan tir CH3COOH dan tdi
sir
tao thanh ion manh m/z 157, ion manh nay tilp tuc
bi phan hoa bang phan cat este lien tiep cho cac ion manh m/z 98 va m/z
115.
Manh m/z
115
phan cat este cho ion manh m/z 73. Mdt kieu phan cat khac
ciia
ion manh m/z

Id 10ml
dung
dich thir nghiem. Nudi cay 18-24 gid ddi vdi vi khuan, cau khuan tren thach Mueller -
Hintin va nam men tren mdi trudng SBR (Sabouro) trong
tii
am
37°C.
Ket qua do dudng
kinh vdng vd khuan do dugc dan ra trong bang 4c. Dan xuat N-glucozit chira di vdng
nito loai
3-glucozylaminoiso-
thiazolo[3,4-d]pirimidin
tdng hgp tir cac dan xuat
ciia
6-
amino-uraxin/thiouraxin khdng cd kha nang khang khuan, trir trudng hgp hgp chat
GAIT8.
Mdt sd hgp chat trong sd nay cd hoat tinh khang nam Aspergillus
niger,
Fusarium
oxysporum va nam men Candida albicans, Saccharomyces
cerevisiae.
20
H H
m/z
98
Sa do
7.
Suphdn mdnh ciia hap chdt GAIPl.
21

0
0
0
0
0
0
0
12
Nam
Aspergillus
niger
8
16
15
13
14
10
9
13
Nam
Fusarium
oxysporum
16
15
13
14
10
9
8
16

axetamido CH3CO-NH d phan tir N-axetyl-D-
glucozamin, chung tdi da sir dung phuong phap co hpc phan tir
AMI
va AMBER dua
tren phin mem HyperChem 7.0 [24]. Van de ve cau hinh cua phan tir N-axetyl-D-
glucozamin d day dac biet dugc chu y d chd, tuang tu nhu d axetamit, nhdm axetamido
cd the d bdn dang cau hinh la (Z)-anti va
(Z)-syn,
(E)-anti va (E)-syn (xem
Hinh
3).
Danh phap (Z) va (E) dua tren
sir
sap xep
ciia
cac nhdm the xung quanh lien ket
N-C(O)
trong khi dd danh phap syn va anti thi dugc xet theo su dinh hudng xung quanh
lien ket C2(H)-N cua nguyen tir hidro
ciia
vdng piranozo va nguyen tir hidro hay
ciia
nhdm the R tren nguyen tir nito-amino. Khi vdng exo nam cimg phia vdi nhdm C=0 so
vdi lien ket C-N thi ta cd cau hinh Z va nam khac phia thi ta cd cau hinh E, cdn danh
phap syn de chi vi tri cua hai nguyen tir hidro dinh vdi C2 va N nam cimg phia vdi nhau
va neu chimg nam khac phia thi se dugc gpi la anti. Cac anome
ciia
N-axetyl-D-
glucozamin
dugc ki hieu nhu sau:

quanh
N-C(O)
CH,
HX
(Z)-syn
(E)-syn
Hmh 3. Cdn bdng nhdn duac bdng su quay quanh cdc lien ket C(H)-N vd N-C(O) a
axetamit
(R=H
hay CH3).
ADGLCNAc-(E)-anti
ADGLCNAc-(E)-syn
ADGLCNAc-(Z)-anti ADGLCNAc-(Z)-syn
Hinh
4. Cdc cdu
hinh
cd thi cd
ciia
nhdm axetamit a
N-axetyl-a-D-glucozamin
(tdi
iru
hod
hinh
hoc bdng phuang phdp
AMI).
23

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