L INTRODUCTION
2. KET QUAVATHAOLUAN
2.7. Ve dieu che D-glucozamin hidroclorua tir vo torn vd chuyin hod thanh 2-
axetamidÓ2-deoxi-/3-D'glucopiranoz(T
Trong ban bao cao nay, chiing toi da su dung vo tom kho lam ngudn nguyen lieu dau de dieu che a-D-glucozamin, qua trinh tach chitin va thiiy phan nhu sau: Trong vo tom dugc su dung nhu la nguon nguyen lieu ban dau dugc mua tren thj truang co chua nhieu tap chat (nhu dau torn, thuc an nuoi tom con sot lai, ...), do vay can phai loai bo cac tap chat nay truac khi decanxi hoạ Cac loai tap chat tan trong nuac dugc loai bo bang each rua vo torn kho nhieu lan bang nuac. Sau do vo tom da rira sach nay dugc ngam trong dung dich NaOH 10% trong 24 gia a nhiet dp phong, rua sach. va tiep tuc ngam trong dung dich HCl 2N de tien hanh decanxi hoạ Su decanxi hoa can tien hanh tu tir de tranh sir mat mat do sui bgt qua muc. Phan can thu dugc mau trang hong dugc rira sach bang nuac va say kho de lay chitin thọ
Chitin tho dugc chuyen hoa tiep thanh a-D-glucozamin ma khong can tinh che truac. Sir thuy phan dugc tien hanh nha tac dung ciia axit clohidric dam dac tren noi each thuy soi trong su6t 2,5 giạ Duai tac dung cua moi truang axit manh. nhom axei\ 1 trong chitin bi thuy phan đng thai vai su phan each cac lien ket 1.4-glicozit trong phan tu chitin. Trong ph6 h5ng ngoai ciia a-D-glucozamin clohidrat xuat hien cac bang song hap
thu rong 6 3100-3350 cm"' dac tnmg cho dao dong hoa tri ciia nhom NH^^ cac bang song hap thu a 1616 cm"' dac trung cho dao dong biSn dang khong d6i xiing va a 1394 cm-1 d§c trung cho dao dong bien dang doi xung ciia nhom naỵ Nhom hidroxi-ancol trong phan tu co cac bang song hap thu a 2393 cm"' dac trung cho dao dong hoa tri cua
nhom -OH (hen hop gi&a cac phan tu), a 1250, 1184, 1140, 1116, 1093 va 1036 cm' dac
' Z I ' ^ I R Z ^ A " " ^ "'" t ^ ' T ^ : 0 - " ^--""g Ph^" t"; Nh6m CH, co cac hip thu d
. , ? \ ^ f 2-axetamido-2-deoxi-p-D-g]ucopiranoza (N-axetyi-p-D-glucozamin)
dugc dieu che bang phuang phap axyl hoa chpn lpc a-D-glucozamin, trong do nhom axy chi dl vao lien ket voi nguyen tu N ciia nhom amino, con cac nhom hidroxi khong bi axyl hoạ Tu a-D-glucozamin ban dau, sau phan ung axetyl hoa nhan duoc 2-axetamido-2- deoxi-P-D-glucopiranoza (N-axetyl-p-D-glucozamin), nhu vay trong qua trinh phan ung
da xay ra su anome hoa nhom hidroxi o Cl tir vi tri axial chuyin din vi tri equatorial
dieu nay cung^phu hprp voi hoa lap the cua cac monosaccarit, vi su co mat cua cac nhom
axetyl cong kenh gan voi nguyen tu nita lien kk vdi C2 lam cho can bang giua hai đng phan a va p cua vong piranozo chuydn dich vk phia ben phaị Trong phd hdng ngoai cua dan xuat N-axetyl-p-D-glucozamin, xuk hien cac bang sdng hdp thu d 3463 cm'' dac
trung cho dao dpng hda trj cua nhdm NH, vach amit 1 (bang sdng hip thu cua nhdm C=0 ) xuat hien a 1628 cm , vach amit II (bang sdng hip thu dao đng bi6n dang cua NH va dao dpng_cua lien ket C-N) xuat hien d 1553 cm', đng thdi cac bang sdng hip thu a 1616 cm va a 1394 cm dac trung cho dao đng biln dang khdng đi xung cua nhdm -NH2 bien mat. Dieu nay chung td ring nhdm NH2 da bi axetyl hdạ Trong phd cdn xuit hien bang sdng hap thu d 3328 cm"' dac trung cho dao đng hda tri cua nhdm hidroxi- ancol d trang thai lien hap (trang thai mlu rin), va su ving mat ciia cac bang sdng hip thii d viing 1710-^1750 cm"' (dac trung cho dao dong ciia nhdm cacbonyl trong este) chung td rang phan ung axetyl hda chpn Ipc d tren da chay tdt: cac nhdm hidroxi-ancol khdng bi axyl hda ma chi cd nhdm amino ciia a-D-glucozamin tham gia phan img.
San pham thu dugc la chat rin tinh thi cd mau tring, ndng chay d 203-205''C. Hieu suit san phim dat 92-96%. Dp quay cue rieng [a]D21 +42° (d diim can bing c 2, nude).
2.2. Tong hop mpt so glucozylamin tir cdc dan xudt cua thiazol vd benzothiazol vd N- axetyl-P-D-glucozamin
Bang each cho dan xuat 2-aminothiazol va 2-aminobenzothiazol vdi N-axetyl-P- D-glucozamin trong etanol 96%, thdi gian phan iing trung binh tir 30-50h se thu dupe cac san pham glucozylamin vdi hieu suit tuang đi cao (50 - 60%).
Phan ling nay la loai phan ung tach nude, nen thdng thudng thi phan img dugc tien hanh trong dung moi khan. Nhung do N-axetyl-a-D-glucozamin la chit it tan trong etanol nen neu tien hanh trong dung mdi etanol khan thi phan img xay ra d dang di the rat khd khan, chinh vi vay phan img dugc tien hanh trong dung mdi etanol 96° vira tao dieu kien cho phan img xay ra de dang vi hgp chat nay nam trong dung dich. đng thdi vdi ndng dp 96% khdng anh hudng den can bang loai nude ciia phan img. Phan img can xiic
tac axit, thong thuong la axit axetic bang. Bdng Ị Cdc hop chdt N-(4-phenylthiazol-2-yl)-2-axetamido-2-deoxi-/3-D- glucopiranozylaminvdN-(benzothiazol-2-yl)-2-axetamido-2-deoxi-P-D- glucopiranozylamin . ^ ^ ^ Cl r. R' ^^ 'S NHGlcNAc
R=H (I), CH3 (II), COOMe (III), COOEt (IV) (V)
•NHGlcNAc GtcNAc = NHAc So TT 1 2 3 4 5 Hgp chat I,R=H II, R=CH3 III, R=COOMe IV, R^COOEt V Dnc, °C 228-230 186-188 220-222 236-238 218-220 Hieu suat,% 50 49 67 58 62 Pho VoH 3455 3459 3447 3365 3459 VNH 3326 3385 3362 3299 3327 long ngoai, cm'' Vc=o 1628 1628 1647 1650 1628 SNH 1549 1550 1562 1562 1549 Vc=0{este) - - 1698 1699 - Cau tnic cua cac N-axetylglucozylamin dugc xac nhan bang each ghi phd hdng ngoai va phd ' H - C H T N . Trong phd hdng ngoai ciia cac N-(benzothiazol-2-yl)-2- axetamido-2-deoxi-p-D-glucopiranozylamin va N-(4-phenylthiazol-2-yl)-2-axetamido-2- deoxi-P-D-glucopiranozyl-amin cd cac bang sdng hap thu dac trung cho cac nhdm the cd mat trong phan tir: nhdm OH d 3459-3365 cm"'( VQH lien hgp); nhdm NH d 3385-3299 cm''; nhdm chiic amit cd cac hip thu vc=o (amit) d 1650-1628 cm''(vach amit I) va 5NH d 1562-1549 cm''. Ngoai ra trong phd cdn xuit hien mdt so bang sdng hap thu dac tnmg cho dao dpng hoa tri ciia lien kit C=C trong nhan di vdng thom d viing 1549-1528 va 1465-1464 cm''.
Trong pho ' H-CHTN ciia cac glucozylamin ndi tren, cd hai viing tin hieu cdng hudng, tuang iing vdi hai loai proton trong phan tir: cac proton trong nhan thom benzen va nhan di vdng thiazol cd cac tin hieu cdng hudng nim trong viing 7.112-8,543 ppm; cac proton cua hgp phin cacbohidrat cd tin hieu cdng hudng d vimg <5 ppm: cac nhdm OH vdi đ chuyin dich hoa hoc d 4,546-5,347 ppm, cac proton no trong vdng piranozo cd do chuyin dich hoa hoc nim trong viing 3,224-4,975 ppm. Proton cua hen ket amit (trong nhdm N-axetyl cua NH-CO-CH3) cd dp chuyen dich hoa hpc nam trong vung
5,768-6,435 ppm. Nhdm amino bac 2 cua glucoz>'lamin cd tin hieu a dang duplet o
8,344-8,534 ppm. Ngoai ra trong phd CHTN cdn cd cac tin hieu dac trung cho cac nhom proton ciia cac nhdm metyl va etyl trong timg phan tu rieng biet.
IIỊ P H A N T H U ^ C N G H I E M
Nhiet đ ndng chay duac do bang phuang phap do mao quan._ Pho hdng ngôi duoc ghi t i n may phd FTIR Magna 760 (NICOLFT. My) ta, Irung tam Hoa hoc Dau ^ ; ; ^ ; H ; . T^Lg BHKHTN) bang J.ng^;.P-^^^^^ ^ - - - -
Vien Khoa hoc va Cong nghe Viet nam).
3,L Diiu chi a-D-glucozamin hidroclorua
Phuang phap dihu che dugc ti^n hanh theo tai lieu [4] tu vo torn khọ Phan ung
thuy phan chitin tho dugc tien hanh theo tai lieu [5].
3.2. Tong hap 2-axetamido-2-deoxi-^D-glucopiranoz(r (N-axetyl-p-D-glucozamin
Phan ung dugc ti^n hanh theo tai lieu [66].
3.2. Tong hop cdc N-(thiazol-2'-yl)- va N-(benzothiazol-2'-yl)-2-axetamido-2-deoxi-/3-
D-glucopiranozylamin
Cho 0,005 moi 2-aminothiazol hay 2-aminobenzothiazol the va 0,005 moi (l,12g) N-axetyl-P-D-glucozamin da dugc nghien min vao 25ml etanol 96° trong binh cau day tron dung tich 50ml. Them vao do 0,3ml axit axetic bang. Hon hgp phan ung dugc dun
hoi luu tren noi each thuy trong vai giạ Cat loai V^^ lugng dung moi, sau do lam lanh
dung dich thi san pham tach ra duoi dang tinh thẹ San pham dugc loc va rua bang etanol va lam kho ngoai khong khị Ket tinh lai tu etanol 96ọ Hieu suat 49-52%.
Ket qua tong hgp dugc dan ra trong bang 1.
4. KET LUAN
Da t6ng hgp dugc 5 hgp chdt cua day N-(4-phenylthiazol-2-yl)-2-axetamido-2- deoxi-p-D-glucopiranozylamin va N-(benzothiazol-2-yl)-2-axetamido-2-deoxi-P-D- glucopiranozylamin b^ng phan ung cua 2-axetamido-2-deoxi-a-D-glucopiranozylamm voi cac hgp chdt 2-amino-4-phenylthiazol hoac 2-aminobenzothiazol the khac nhau trong su CO mat cua xuc tac axit axetic bang. CAu true cua cac san pham dugc xac nhan bing cac du kien phd hdng ngoai qua bang song hap thu a vung 3385-3299 cm d^c trung cho dao dgng hoa tri cua nhom amino bac haị Proton cua lien ket amit co tin hieu cong huang a 5,768-6,435 ppm. Nhom amino bac 2 cua glucozylamin co tin hieu cong huong a dang duplet a 8,344-8,534 ppm.
Cong trinh duac hoan thank vai su tdi tra kinh phi cua Tnmg tdm Ho tra Nghien cuu chau A (Dai hoc Qudc gia Ha Noi) vd Di tdi nghien cuu cap DHQG Ha Soi, ma so QT-05-16.
TAI LIEU THAM KHAO
1. Paul Fowler, Bruno Bernet and Andrea Vasella A ' H - N M R Spec^ros^^^
Investigation of the Acetam.do Group m ^^-^^^J"'''^^^^^^^^^^
Allosamine and D-Glucosaminẹ Heiv. Cl.m. Actạ. 79. ^V_^^^^^^ ^^^ ^_
2 Karim Mazeau Serge Perez and Marguerite Rinaudọ Pred ctcd intlucnụ ol .%
'• ^Ty^ G ^ r C — on the - n ^ r m . ^ a l F.ten.,on oi Chum and Chnosan Chains, J. Carbohydr. Chem.. 19 (9). PP^ - ^ f j " ^ ' , " j,,,,,,,,,,, , , , „ . , , ,/„ 3. Buyong Mạ Henry F. Schaeter III ^^^^^^J^^n- ạul P-kcol... ... Am,
potential energy surfaces and composuun, o1
Chem. Soc, 120,3411-3422(1998). ^ . ^ . ^ , , . , . . , , ,
4. Nguyln Dinh Thanh Dang Nhu Tai, Dang Quoc Cuong, Gop phan nghien cuu tach
2-amino-2-dezoxi-a-D'glucoza tit vo torn, Tap chi Hoa hgc va Cong nghiep hoa chat,
Nọ5, 8-10(1998).
5. M. Stacey and J.M. Webber, Methods in Carbohydrate Chemistry, Reaction of
Carbohydrates, vol.1 , Ed. R.L.Wistler and M.L. Wolfrom, Acad. Press, N.Ỵ, p.
228-230(1962).
6. D. Horton, Methods in Carbohydrate Chemistry, General Carbohydrate Methods,
HOl NGHI KHOA HQC vA CONG NGHE HOA HlTU CO TOAN QUOC LAN THÚ III