Tổng hợp và thử hoạt tính sinh học của 5-(p-fluorobenzyliden) thiazolidin-2,4-dion và một số dẫn chất base Mannich

Nghien CLPU - Ky thuat<br /> Ket luan Gac aril oils were preserved by Propyl gallate<br /> K i t qua nghien CLPU d6 on djnh cua lycopen vS 0.1% & 0.5%) and four conditional factors were<br /> p- caroten trong miu d i u gie dugc bao quan 6' chosen to monitoring the changes in content of<br /> eae diiu kien tren cho thiy miu duge bao quan a lycopen and P- carotens. With Propyl galate 0.1%)<br /> diiu kien nhiet dp lanh 5 ± 3°C, co sue khi nita va & 0.5%) added as presevative agent, the Gac aril<br /> trpn propyl galat thi ham lugng lyeopen va P- oils were best reserved in nitrogene atmosphere<br /> earoten giam di it han nhiiu so vo'i bao quan 6' cac at cool temperature and kept from light.<br /> diiu kien khae trong eung mot tho'i gian. Mat khac Tai lieu tham khao<br /> d i i vo'i miu bao quan 6' diiu kien eo trpn them 1. Trinh Van Lau, Huang dan cua Asean ve<br /> propyl galat va sue khi nita thi ham lugng giam it nghien cuu dp on djnh cua che pham thuoc, Vipn<br /> han so vai cung diiu kien ma khong trpn propyl Kiem nghi$m thuoc Trung wang, (2002).<br /> galat. Miu diu gie eo trpn 0,5% propyl galat co kha 2. Nguyin Tuang Vy, Nghien cuu thanh phan hoa<br /> nang bao quan lycopen va p- caroten tit han so vo'i hoc va gop phin tieu chuan hoa chat lugng dau gac<br /> miu d i u gie ehi trpn 0,1% propyl galat. Vay qua Viet Nam dung lam thuoc, Luan an tien sy. Truang<br /> kit qua nghien CLPU ban diu cho thiy propyl galat DH Duvc Ha Noi, (2008).<br /> CO tac dung ngan can qua trinh oxy hoa cua 3. Nguyin Tuang Vy, Tran TLP An. Dp on djnh cua<br /> lyeopen va p- caroten trong miu d i u gie. mot so hap chat c6 hoat tinh sinh hoc trong dau gac Viet<br /> Nam. Tap Chi Dwac hpc, so 405 thang 1/2010, tr15.<br /> Summary 4. L.T.Vuong and J.C. King. A method of<br /> Of valuable components of the Gac aril oils preserving and testing the acceptability of Gac fruit<br /> (Lycopen, j3- caroten, vitamin E, ...), Lycopen and oil. a good source of beta carotene and essential fatty<br /> acids. Food and Nutrition Bulletin. (2003), 24. N°. pp<br /> P-carotenoid proved highly sensitive to light,<br /> 224-230.<br /> temperature and oxidation. Lyeopen decreased to<br /> 5. C. H. Lin. B. H. Chen. Stability of carotenoid in<br /> 65% and p-caroten to 68% after 3 months' tomato juice during processing. Eur food<br /> storage in natural air and at room temperature. Resteehnol,(2005), 221: 274-280.<br /> <br /> <br /> <br /> <br /> Tong hop va thir hoat tinh sinh hoc cua<br /> 5-(/;-fluorobenzyliden)thiazoIidin-2,4-dion<br /> r fv r<br /> <br /> va mot so dan chat base Mannich<br /> Dinh Thj Thanh Hai, Bui Thj Thanh Cham<br /> Bp mon Hoa huu ca - Truang dai hoc Duac Ha Noi<br /> <br /> Dat van de Rosiglitazon (biet duge: Avandia). T i i p tue phSt<br /> Thiazolidin-2,4-dion va d i n c h i t da dugc cac triin huo'ng nghien cuu v i thiazolidin-2,4-dion,<br /> nha khoa hpc trong va ngoai nuo'c nghien cuu trong bai bao nay chung t6i trinh bay k i t qua<br /> mot each co he thing v i ting hgp hoa hpc va ting hgp va thu hoat tinh khang khuan, khang<br /> tac dung sinh hpc. Nhiiu c6ng trinh nghien cuu nim, khang t i bao ung thu cija 5-(p-<br /> cho thiy cac d i n chit cua thiazolidin-2,4-dion fluorobenzyliden)thiazolidin-2,4-dion vS mot s i<br /> CO hoat tinh khang khuin, khang n i m , khang t i d i n chit base Mannich.<br /> bao ung thu, chong tiiu duo'ng '^"^'. IVlpt s i d i n K§t qua va ban luan<br /> c h i t cua thiazolidin-2,4-dion da dugc su dung Tong hgp hoa hoc<br /> trong y hpc lam thuic diiu trj dai thao duo'ng Cac d i n c h i t cua thiazolidin-2,4-dion dugc<br /> nhu Pioglitazone (biet duge: Aetos, Dopili) va ting hgp theo sa d i phan ung sau day:<br /> <br /> <br /> TAP CHI DUOC H O C - 11/2010 (SO 415 NAM 50) 25<br />  Nghien CLPU - Ky thuat<br /> <br /> CHO F<br /> -NH , 3-N-CH2NR1R2<br /> HCHO + HNRiR<br /> ^ O CH'^S ~^f<br /> <br /> Thiazolidin-2,4-dion 2-10<br /> Chat -NR1R2 Chat -NR1R2 Chat -NR1R2<br /> <br /> /C2H5 / \<br /> 2 5 8 -N 0<br /> "™ \ 0 / ™ ' V2H5<br /> <br /> / \<br /> 3 6 -N(CH3)2 9 -N N-CH3<br /> -HN-/(^\-F<br /> <br /> .NO2<br /> 4 _ H N - ^ ^ C I<br /> 7 10<br /> -0<br /> Tong hap 5-(p-fluorobenzyliden)thiazoiidin- Tong hap mot so din chat base Mannich<br /> 2,4-dion (1) (2-10) '<br /> Tong hgp 5-(p-fluorobenzyliden)thiazolidin- Tong hgp eae dan c h i t base Mannich eua 5-<br /> 2,4-dion (1) bing phan ung ngung tu cua 4- (p-fluorobenzyliden)thiazolidin-2,4-dion (2 - 10)<br /> fluorobenzaldehyd vai thiazolidin-2,4-dion trong bing phan ung eua c h i t (1) vo'i formaldehyd va<br /> dung m6i acid acetic bang, xuc tac natri acetat eae amin (p-toluidin, p-fluoroanilin, p-eloroanilin,<br /> khan, nhiet dp phan ung 118 - 123°C. Theo doi diethylamin, dimethylamin, m-nitroanilin,<br /> phan ung bing s i c ky lo'p mong (SKLM) de xac morpholin, N-methylpiperazin, piperidin,) trong<br /> dinh tho'i gian phan u'ng thich hgp. K i t qua da dung m6i ethanol, nhiet dp phan Crng 60 - 70°C.<br /> ting hgp dugc d i n chit ngung tu eua 4- Cac phan LPng dugc theo doi bing SKLM de<br /> fluorobenzaldehyd vai thiazolidin-2,4-dion (1) xac djnh tho'i gian phan ung thich hgp. K i t qua<br /> vo'i hieu suit va mot s i hing s i vat ly dugc ghi da ting hgp duge 9 d i n chit base Mannich (2 -<br /> 6' bang 1. 10) vai cac s i lieu ghi a bang 1.<br /> <br /> Bang 1 : Kit qua tdng hap cac chit 1 - 10<br /> Thoi gian Nhiet dp Dung m6i Diem chay Hieu suat<br /> Chat CTPT KLPT<br /> phan wng (gia) phan wng (°C) ket tinh lai ("O '(%)<br /> 1 CloHsOzNSF 223 5 118-123 Ethanol 222 - 224 71,5<br /> 2 C18H15O2N2SF 342 2,5 65 Ethanol: CHCl3(2:1) 145-147 51,1<br /> 166,5-<br /> 3 C17H12O2N2SF2 346 2,5 65 Ethanol: DMF(5:1) 65,0<br /> 168,5<br /> 4 C17H12O2N2SFCI 362 2,5 65 Ethanol: CHCl3(5:1) 158- 161 70,5<br /> Ethanol:<br /> 5 C15H17O2N2SF 308 2 60 CHCl3(6:1) 53,5<br /> 167-170<br /> 6 C13H13O2N2SF 280 2 60 Ethanol: CHCl3(6:1) 160- 162,5 57,1<br /> 7 C17H12O4N3SF 373 2,5 70 Ethanol: DMF(1:1) 202 - 205 75,0<br /> 8 C15H15O3N2SF 322 1,5 60 Ethanol 135-137 65,2<br /> 9 C16H18O2N2SF 336 1,5 60 Ethanol 176-177 74,6<br /> 10 C16H17O2N2SF 320 1,5 60 Ethanol 130-140 75,0<br /> <br /> Dp tinh khiit eua cac chit ting hgp Qwcfc da qua phan tich p h i IR, WIS, ''H - NMR, ''^C - NMR<br /> dugc sa bp kiim tra bing do nhiet d6 nong chay va duge trinh bay a bang 2, bang 3 va bang 4.<br /> SKLM. Cau true eua 10 chit (1-10) duge xac nhan P h i IR eua 10 c h i t (1 - 10) d i u co dai h i p<br /> qua phan tich pho IR, MS, ' ' H - N M R , " C - N M R . Kit thu dae trung cho dao d6ng h6a tri cua nhom<br /> <br /> <br /> 26 TAP CHI DU'GC HOC - 11/2010 (SO 415 NAM 50)<br />  Nghien CLPU - Ky thuat<br /> >C=0 (1747 - 1675cm"''). C^c base Mannich thgm (3343 - 3427cm'Y lien k i t C=C<br /> d i u c6 dao d6ng hoa tri cua nh6m -CH2- a ethylenic IS li^n k i t dugc tao ra sau phan ung<br /> hgp p h i n aminomethyl trong vung (2975 - ngung tu d i u x u i t hien trong p h i IR eua c h i t<br /> 2900em"^ va 2863 - 2831cm''') chung to phan ngung tu va eSc d i n c h i t base Mannich tong<br /> LPng Mannich da xay ra. P h i IR eua 4 c h i t (2, hgp dugc, dai h i p thu eua lien k i t C=C tham<br /> 3, 4, 7) CO dai h i p thu -NH eua hgp p h i n amin trong vung (1614 - 1584cm"^).<br /> Bang 2: Sd lieu phd IR va MS eiJa eae chit tdng hap dwac<br /> ^ Pho IR (KBr),, cm"' Pho khoi<br /> Chat VNH VCH2 vc=o VCjj^r Vc-F (M')<br /> 1 3155 1729 1700 1593 1240 223<br /> 2 3343 2922 1747 1675 1594 1239 342<br /> 3 3424 2893 1735 1684 1593 1242 346<br /> 4 3427 2900 1731 1686 1593 1241 362<br /> 5 2975 1745 1681 1597 1236 308<br /> 6 2967 1739 1684 1596 1238 280<br /> 7 3413 2919 1736 1676 1593 1238 373<br /> 8 2955 1742 1682 1597 1243 322<br /> 9 2949 1712 1688 1601 1248 336<br /> 10 2944 1744 1690 1598 1241 320<br /> P h i khii lugng eua 10 c h i t t i n g hgp duge ngung tu) eo pic c6 dp chuyen djch h6a hpc 8 =<br /> (1 - 1 0 ) CO pic phan tO eo s i k h i i phu hgp vai 12,6ppm eua proton NH amid. Cac d i n c h i t<br /> so khii eua c6ng thCpc du k i i n va tuan theo base Mannich t i n g hgp duge ( 2 - 1 0 ) d i u x u i t<br /> "quy t i c nita", tren p h i d i MS eo eae pic cua hien pic tuang ung vo'i proton - CH2- eua hgp<br /> cac ion manh dac trung phu hgp vo'i sa d i phin aminomethyl dugc tao ra sau phan ung<br /> phan manh. Mannich trong khoang 4,567 - 5,154ppm. P h i<br /> K i t qua phan tich p h i ^ H-NMR eua 10 chit cpng huang tCp ''^C-NMR eua b i n c h i t 1, 4, 8,<br /> ting hgp dugc (1 -10) cho thiy tren p h i d i eua 10 dugc ghi p h i cho t h i y eae c h i t nay co s i<br /> eae chit co d i y du tin hieu cua cac proton co carbon va dp chuyin djch hoa hpc 5 eua cac vj<br /> trong phan tu. P h i ^H-NMR cua chit 1 (chit tri carbon phu hgp vo'i cong thu'c d u kiin.<br /> Bang 3: Sd lieu phd ^H-NMR eua eae chit tdng hap dwac<br /> Chat ^H-NMR (DMSO-de), 5 (ppm)<br /> 1 12,6(s, 1H, >NH); 7,792(s, 1H, - CH=); 7,669 (t, 2H, H-3', 5'); 7,385 (t, 2H, H-2',6')<br /> . 7,941 (s, 1H, -CH=); 7,691 (t, 2H, H-3', 5'); 7,386 (t, 2H, H-2', 6'); 7,003 (d, 2H, H2-,6-); 6,732 (d, 2H, Hy.s-);<br /> 5,082(d, 2H, -CH2-N