DAI HOC QUOC GIA HA N p i TRU'OfNG DAI HOC KHOA HOC TU'NHIEN KET QUA THUC HIEN DE TAI NGHIEN CtTU KHOA HOC TRONG DIEM CAP DAI HOC QUOC GIA HA NOI "NGHIEN Ciru TONG HOP, HOAT TINH SINH HpC (KHANG K H U A N , CHONG VIEM, CHONG UNG THU) VA KHA NANG iTNG DVNG CUA MpT SO XETON a,P - KHONG NO CO C H I T A NHAN DI VONG: INDOL, FURAN, CUMARIN, QUINOLIN" Ma so: QGTD-05-03 Chu nhiem dl tai: GS.TSKH NGUYEN MINH THAO Cac can bo tham gia: + PGS.TS Nguyen Dinh Thanh + PGS.TS Tran Cong Yen + TS Lull Van Chinh + ThS Pham Van Phong + ThS Nguyen Thj Minh Thir + ThS Tran Van Tinh » + KTV Le Thj Minh Nguyet + Mot so NCS, HVCH va sinh vien DAI HOC QUOC G\A HA NOI TRUNG TAM THONG TIN THU VIEN o:}C(,cccoc^ Ha Noi - 2007 - Qtkdnt ide glA thjUe^ kiin djt tiki nd^ jeut ehdjt thdnh ednt iUt (Biut ^idnt d£^ ^an Xtufa h^ od ©dng, nqht, ^dit fJtdnQ, ad ^hdnjg, ^di oa,, ^ai twe QJUM QJH JCd MI dd ghuy dt tdi od tac- ntol tDlst ltli§t ihttan Hht gidp, dS ehung tdi hodn thdnh ahltnt OVL - &fdng tdi edng, xin ehdn thdnh edm dn (Ban^ ^Idnt hltUf ^hong, JChoa, hne od ©ong, ttghe^ ^radng ^ql hoe Xho4L hoe Q^U nhiin ~ ^'JCQ/Q, "JCd Qtdl dd ddng olin, dng ho od gluft dd ehdng tdi hodn thdnh de tdi ndg, - &uing idl edng xin ednt tUt ^ttdng nghien edu eau true - ^len 'Xod ttoe; ^hong Q'ku' nghiem Itoal linh tinh hoe - ^len JCod tioe ede ho^ ehdi thien nhien eun ^len JChou hoe od ©ong nghe ^lel Qtant; ^Itong Qtghlen edu p-Dimetylamino benzandehit 263 - 264 35 3300 1732, 1619 976 II, Salixylandehit 259 - 260 30 3215 1720, 1629 973 II, Piperonan®ehit 258-259 45 3357 1740, 1632 981 III Indol-3-andehit 298 - 299 70 3224 1726, 1623 975 II, 5-(p-Nitro phenyl)-fufural 344 - 345 25 3221 1741, 1622 978 1514, 1337 (NO2) II2 Piperonandehit 279 - 280 40 3350 1732, 1641 965 1194 (COC) II2 Indol-3-andehit 300-301 65 3227 1717, 1632 953 II2 2-Metyl indol-3andehit 309-310 60 3216 1711, 1629 976 II2 5-(p-Nitro phenyl)-fufural 301-302 27 3345 1735,1634 970 1530, 1353 (NO2) 1139(COC) 3130 NHindoI 3106 (NHindol) 3195 (NH^doi) 1545, 1333 (NO2) Tren ph6 hong ngoai ciia cac xeton a, P-khong no co cac vach dac trung cho dao dpng hoa tri cua nhom CO xeton lien hop a khoang 1619-1641 cm"\ cua » nhom CO lacton a 1711 - 1741 cm\ ciia nhom OH phenol a 3216-3357 cm"' va ciia nhom chuc khac co mat phan tii Dac biet tren ph6 xuit hien vach a khoang 953-981 cm"' ma chiing toi cho ding dac trung cho dao dong bidn dang khong phing cua nhom vinyl a cau hinh trans, Phd cong huang tu proton cua mot so xeton a,p-kh6ng no cho thay ngoai cac tin hieu dac tnmg cho chuySn dich hoa hpc cua cac proton thong thuang thi da thSy mat di tin hieu proton ciia nhom metyl axetyl va xuat hien tin hieu cua proton nhom vinyl duai dang vach doi khoang 7,91 - 8,31 va 7,74 - 8,03 ppm vai hi^u ung mai nha va hing s6 tucmg tac spin - spin giua hai proton la 15 - 15,5 Hz, ma diSu mot lin nua chung minh cho cau hinh trans ciia nhom vmyl Cac du kien v^ ph6 ' H - NMR dupc trinh bay bang Bang 2: Du kien ' H - NMR ciia mpt s6 xeton a,p-kh6ng no Pho 'H-NMR(5ppm) N(Oi,>: X4 Q^i CX)CH=CH X< Xe X, Oil 13,04(s,lH, OH); 8,64(d, IH, Cg-H, J=9,0 Hz); 8,12 va 7,95 (d, 2H, -CH=CH, J=15,5 Hz); 7,96(m, 2H, C,o-H va C,4H); 7,50(m, 3H, C,,-H, C,2-H, Cu-H); 6,99(d, IH, CT-H, JO-9 Hz ); 6,27(1H, C3-H); 2,68(3H, CH3) 13,76(1H, OH); 8,59(d, IH, Cg-H, J=9,0 Hz); 7,93 va 7,83 (d, 2H, -CH=CH-, J=15 Hz); 7,82(d, 2H, C,o-H va C13-H, J=9,5 Hz); 6,95(d, IH, C7-H, Jo=9 Hz); 6,78 (d, 2H, C,,-H, C,4-H, J=9,5 Hz); 6,28(1H, C3-H);3,05(s,6H,-N(CH3);2,65(3H,CH3) 10,42(1H, OH); 9,95(s, IH, C,o-OH); 8,53(d, IH, Cg-H, Jo=9 Hz); 8,28 va 8,03(d, 2H, CH=CH, J=15,5 Hz); 7.97(d, IH, C7-H, J=9 Hz); 7,33(m, IH, C,,-H); 6,97(m, 2H, C,2-H va C,3-H); 6,91(m, IH, C,4-H); 6,28(s, IH, C3-H); 2,64(3H, CH3) 9,80(1H, OH); 8,61(1H, Cg-H); 7,95 va 7,88 (d, 2H, -CH=CH-, J=15,5 Hz); 7,75(1H, C,o-H); 7,41(1H, Cn-H); 7,03(1H, C7-H); 6,95(1H, C,4-H); 6,26 (IH, C3-H); 6,13(2H, C,5-H2); 2,68 (3H, CH3); 13.85(1H, OH); 12,13(1H, NHi„doi); 8,57(1H, Cg-H, J=9 Hz); 8,31 va 7,74(d, 2H, CH=CH, J=15 Hz); 8,26(1 H, Cio-H); 8,17(m, IH, C,5-H); 7,52(m, IH, C,2-H); 7,28(m,2H, Cu-H va CH-H); 6,26(s, IH, C3-H); 2,65(3H, CHi) 12,08(1H, OH); 9,95(1H, NH); 8,32(1H, C9-H); 8,23(1H, Cg-H); 8,20 va 7,80(d, 2H, CH=CH, J=15,5 Hz); 8,09(1H, C,5H); 7,52(1H, C,2-H); 7,27(m, 2H, C,3-H va C14-H); 6,89(1H, C5-H); 6,25(1H, C3H);2,51(3H,CH3) 9,81 (IH, OH); 8,38(1H, Cg-H); 7,91 va 7,82(d, 2H, CH=CH, J=15,5Hz);7,68 (lH,C,o-H);7,40(d, IH, C,3-H) ;7,03(d, IH, C,4-H); 6,90(1H, Cs-H); 6,28(1H, C3-H); 6,15(2H, C,5-H2); 2,54(3H, CH3) Pho khdi lupng cua mot s6 xeton a,p-kh6ng no d^u cho pic ion phan tu co so khdi trung vai phan tu khdi cua hop chit va cac ion manh tuong ung Ching han vai X^ cho pic 446 (M + H)"" (Phan tu khdi la 445, ghi theo phuang phap LCMS), 316, 288, 243, 221, 203, 170, 144, Mdt sd xeton-a,p-khdng no da dupc thu hoat tinh sinh hpc ddi vdi ciu khuan Gr (+) (staphylocc epidermidir), true khuin Gr (-) (E.coli) va chong nim Candida albican Phuang phap thu nghiem theo dupc dien, nghia la pha ch^ chit thir nghiem a ndng dp 0,001 gam 500 jil rdi chim dung dich chit thu nghi?m vdi lupng 50 hay 100 ^1 len n6n thach da dupc ciy vi khuin va d^ vao tii am thdi gian thich hpp Hoat tinh khang khuin dupc danh gia theo dp ldn ciia dudng kinh vdng trdn vd khuin Kk qua dupc gidi thieu d bang Bang 3: Hoat tinh khang khuin khang nim cua mdt sd xeton a,P khdng no Stt Mau xeton X, X3 X4 X5 X6 Dudng kinh vdng trdn vd khuan E.Co i(gr-) Staphyl.Epid(gr+) Candic a.albican 50^1 100 Ml 50^1 100 ^1 50^1 100^1 15 20 14 0 14 20 16 20 15 21 0 0 21 15 16 0 14 20 0 0 Nhu vay chii yeu cac xeton a,p khdng no chi tac dpng ddi vdi vi khuan gr- T H V C NGHIEM Phd hdng ngoai dupc ghi tren may FT-IR 1801 Shimadzu tai khoa Hoatrudng Dai Hpc Khoa Hpc Tu Nhien-Dai Hpc Qudc Gia Ha Ndi theo phuang phap ep vien vdi KBr Pho cdng hudng tir proton ghi tren may DRX 500 Brucker dung mdi DMSO-Dg Pho khdi luong ghi tren may MS-Engine 5989HP deu d phong nghien cuu ciu tnic-Vien Hoa Hpc-Vien Khoa hpc va Cdng nghe Vi^t Nam Hoat tinh sinh hpc dupc thu nghiem tai Benh vien 19-8 Bd Cdng An Chat dau 2,4-dihdroxi axetophenon dupc tdng hpp theo tai lieu^'*'^^ *)Tdng hop 6-axetvl-5-hidroxi-4-metvlcumarin (IIi) Cho vao binh ciu hai cd cd lap sinh han hdi luu va nhiet ke 80 ml nitrobenzen va 13,5g AICI3 khan Dun ndng hon hop tdi chat ran tan het De ngudi dSn lOO^C roi them ti6p vao phan ung 7,6g (0.05 moi) 2,4-dihidroxi axetophenon va 6,5 g (0.05 moi) etyl axetoaxetat Hdn hop dupc dun nong tdi I55-160*^C va giiJ d nhiet dp h Lam lanh hdn hop phan ung rdi them vao 10-15 ml axit HCI dac De yen 30 phiit, cit ldi cudn hai nudc dk loai nitrobenzen San pham cdn lai binh dupc Ipc hiit, lam khd, k6t tinh lai tir ^ ! T ' "t^ dupc 4,5g ( 41%) dang tinh thg mau tring sang t'nc 165-166'C (theo tailieuf^J,tncl66**C) & e nc v *)Tdng hap 6-axetvl-7-hidrQxi-4-metvlcumarin riL) Cho vao binh ciu hai cd cd lip sinh ban hoi luu va nhiet k8 3,4g (0,022 moi) 2,4- dihidroxyaxetoj)henon, 2,3 ml (0,022 moi) etyl axetoaxetat, 1ml POCI3 va 10 ml nitrobenzen Hdn hpp dupc khuiy d nhiet dp phdng rdi cit ldi cudn hai nudc dl loai nitrobenzen Dd ngudi,san phim tach dang ket tiia dupe Ipc hiit, de khd,kSt tinh lai tu etanol Thu duac l,5g (32%) san phim dang tinh the mau nau xam,t"ne = 211-212'C (theo tai li^u ^'\ t\, = 212'C) *)Phuomg phap chung tdng hop cac xeton a.p-khdng no (III., ) Dun hdi luu hon hpp ddng sd moi ciia dan xuit 6-axetylcumarin vdi andehit tham clorofom va vai gipt piperidin lam xiic tac 5-6 h San phim ket tiia dun ndng Lpc hiit kk tinh lai bing hon hpp dimetylfomamit: etanol (1:1) Cac xeton a,P-khdng no dupc gidi thieu d bang KET LUAN Bang phan urng ciia 2,4-dihdroxi axetophenon vdi etyl axetoaxetat dieu ki^n khac da tdng hpp dupc 6-axetyl-5-hidroxi-4-metylcumarin va _6axetyl-7-hidroxi-4-metylcumarin, ma tir dd ngung tu vdi cac andehit tham da nhan dupc mdt day cac xeton a,p-khdng no Mdt sd chiing da cd hoat tinh khang khuan dang chii y Cau tao ciia cac san pham nhan dupc da dupc xac dinh nhd phd hdng ngoai, phd cdng hudng tir proton va phd khdi lupng Cdng trinh ndy duac hodn thdnh vdi su giiip da kinh phi cua De tdi diem QGTD-05-03 cua Dgi hoc Qudc gia Hd Ndi TAI LIEU THAM KHAO 1) V.F Traven,N Ya.Podhaluzina,A V Vasiliev,A V.Mamaev.Arkivoc, voll,Part6, ht ml.93I(2000) 2) Nguyen Minh Thdo Pham Vdn Phong Nguyen Xudn Tic, Proceeding of 8r Eurasian conference (EuAs C2S - 8), October 2T' - 24" , Hanoi - Vietnam, Session of org Chemistry.pp.l5 3) Nguyen Minh Thdo, Phgm Vdn Phong Dd Duy Thang, Nguyen Xudn Tu Tgp chi Hod hoc, T.43, S6 3,trJ26 (2005) 4) "Organic Synthesis " - Vol3, p 761 5) Nguyen Minh Thdo, Phgm Vdn Phong, Hodng The Thdng, Ddo Thi Thdo Tgp chi hod hoc T.42 So 1, tr.93 (2004) 6) S.M Sethna R.C.Shah, J Chem Soc 228 (1938) 7) R.D Desai, M Ekhlas Proc Indian Acad Sai (A), 567 (1938); CA 33 3356 (1939) OAI HQC QUOC GIA HA NQI T a p chi K h o a hoc H : ,84-4-7547902 CONG HOA XA HOI CHU NGHIA VIET NAM Doc lap - Ty • Hanh phuc Hd Ngi, Ngdy 30 thdng ndm 2007 GIAY NHAN BAI Kmh gui Quy tdc gid: Nguyen Minh Thao, D6 Tidfn Dung Nguyin Xuan Tii, Nguyin Thi Thu Trang Thay mat Ban Bien t$p, chung t6i xin th6ng bao d^ quj^ tdc gia biet rSng Toa soan da nhan dixcfc v^ da guri di phan bien ban thao bai bao: NGHlfeN CtJtJ PHAN tJNG CUA 8- AXETYL-7-Hn)ROXY-4METYLCUMARIN \6l CAC ANDfiHir THOM Moi thdng tin lien quan deh viec dang tai cua bai bao se sdrm dugc thSng bao cho Quy tac gia Xin chan cam an va ra't mong dirge si/hgp tac ti^p tuc tixcmg lai, T A SOAN TAP CHI NGHIEN CUtJ PHAN I T N G CUA 8- AXETYL-7- HIDROXI-4METYLCUMARIN V d l CAC ANDEHIT THOHVI (Study on reaction of 8- acetyI-7- hydroxy- 4- methylcoumarine with aromatic aldehydes) Nguyen Minh Thdo, Dd Tien DUng, Nguyen Xudn Tic, Nguyen Thi Thu Trang Khoa Hod - Truang Dgi hoc Khoa hoc tu nhien - DHQGHN Summary In this study we found that the reaction of 8- acetyl-7- hydroxy-4- methyl coumarine with aromatic aldehydes gived a,^ unsaturated ketones or products of Michael reaction depending on the characteristic of substituted groups in the aromatic aldehydes The results is confirmed by IR , ^H- NMR and MS spectroscopic data Trong tai lieu tham khao [1] va mdt sd cdng trinh trudc day [2,3], chiing tdi da thdng bao ve su tdng hpp 8- axetyl-7- hidroxi-4- metyl cumarin va phan ung ngung tu ciia nd vdi cac andehit tham de tao cac xeton - a,p -khdng no df bai bao chiing tdi du dinh tiep tuc phat trien phuang hudng dd, nhung th\rc te chung tdi da tim thay ring ngoai cac xeton - a,p - khdng no binh thudng, phan ung cdn tao cac san pham theo kieu cua phan img Michael, thudc vao ban chat nhdm the vdng tham ciia hpp phan andehit: Ar- R j Rl: Nhdm the day e R2: Nhdm the hiit e Ddi vdi cac andehit tham khdng cd nhdm hiit electron phan tii ( pdimetylamino-benzandehit, salixylandehit, piperonandehit va furfiiral) phan ung chi dan thuSn din tdi su tao cac xeton - a,p - khdng no ( IM) Ket qua dupc gidi thieu d bang Tren phd hdng ngoai cua cac xeton - a,P - khdng no nhan dupc cac vach dac trung cho dao ddng hoa tri cua nhdm OH phenol d 3392 - 3520 cm"\ cua nhdm CO lacton d viing 1714- 1750 cm"', ciia nhdm CO lien hap d 1610- 1631 cm'', va dac biet cd vach dac trung cho dao ddng bidn dang khdng phang cua nhdm trans-vinyl d 943- 974 cm'' , Tren cong huomg tii proton cua hai (I, va I2) s6 xeton- a,p Khong no deu thay mat di tin hieu cua cac proton nhom CHj-axetyl, lai thay xuat hifn tin hieu ciia mot cap vach doi 7,23 - 7,27 va 7,04 - 7,90 ppm CO dang hi?u ung mai nha vcri hang s6 tuong tac spin - spin J=16Hz, noi len cSu hinh b-ans cua nhom vinyl Ngoai tren ph6 co cac tin hieu dac trung cho chuyen dich hod hoc cua cac proton khac phan tii Pho khoi lugng cua xeton I, va I3 dhu cho pic ion phan tu co s6 khdi trung vai phan tu khoi ciia phan tu (NT ciia I, = 349, M^ ciia I3 = 350) B a n £ l : Cac xeton - a,p - khong no( I,^) STT rnc (*C) R,Ar (D R; Ph6 IR, cm' HS % Vco Vco VoH Lacton Xeton 8-CH= p-Dimetylaminophenyl 218-220 0,89 63 3437 1714 1610 950 0- Hidroxiphenyl 236-238 0,83 57 3392 1723 1615 943 3,4-Dioximetilenphenyl 237-239 0,87 47 3520 1728 1629 970 Furyl-2 168-170 0,82 43 3457 1750 1631 974 (m/z) M 349 349 350 350 (Ban mdng silicagen, he dung mdi cloroform: etylaxetat 5:1) Nhung ddi vdi benzandehit va cac andehit day benzen cd nhdm hiit electron ( p-clobenzandehit, p-nitrobenzandehit va m-nitrobenzandehit) thi phan ung cua chiing lai xay theo kieu phan ung Michael, nghia la liic dau mdt phan tu metylxeton phan ung vdi mpt phan tu andehit tao phan tu xeton - a,p - khdng no, nhung ti^p theo mpt phan tii metylxeton thu hai cdng hop vao ndi ddi ciia xeton a,p - khdng no dd cudi cimg tao san pham theo kieu phan ung Michael, d day cd le anh hudng cua nhdm hiit electron lam cho kha nang cdng hop ciia cac cacbanion ( nhdm metylxeton mdi trudng baza) vao nhdm andehit tang len, vay phan ung khdng dung d su tao xeton - a,p - khdng no dan thuan K6t qua duac gidi thieu d bang Bang 2: Cac san pham cua phan ung Michael STT (II) RaAr Phenyl p- Clophenyl rnc ("C) 238-240 211-213 Ph6 IR, cm' HS % VoH Vco Lacton Vco Xeton 0,68 0,42 3470 1725 1627 0,75 0,36 3430 1734 1619 Rf* Nhom khac p-Nitrophenyl 243-244 078 0,53 3530 1740 1621 m-Nitrophenyl 221-223 0,76 0,48 3390 1727 629 1517,1347 (NO,) 1530,1345 (NO2) (Bdn mong silicagen, he dung moi cloroform: etylaxetat 5:1) Tren cong huomg tir proton ciia hai ( II2 va II3) s6 bdn hop ch§t cho thay mat di tm hieu ciia nhom CH3 axetyl va cung khong co tin hieu hai vach doi cua nhom trans-vinyl nhu cac xeton - a,p - khong no Mat khac lai xnk hien tin hieu a 3,62-3,85 ppm ciia 4H va 3,93-4,21 ppm cua IH D i k cho thiy san pham CO cau tao nhu sau: CH- Vai cong thiic thi cong huong tir hoan toan phii hgp va giai thich dugc hau het cac pic, dac biet giai thich hgp ly dugc cac dinh viing 3,4- 4,3 ppm Bang 3: Cac tin hieu dac trirag H- NMR cua II2 va II3: OH HO ,CH2-C»-CH2, aJK „ H3C X STT X Cl N02 5-ppm(S6 proton, J-Hz) 2.43s(6H-CH3); 3.62d(4H-CH2); 3.93(1H-CH); 6.12(2H-C3); 6.88d(2H-C5;9), 7.23d(2H-C2.,C6;8.5); 7.37d(2H-C3,C4;8.5); 7.65d(2H-C6;9); 13.20s(2H-OH) 2.41s(6H-CH3); 3.45(4H-CH2); 4.21(1H-CH); 6.15(2H-C3); 6.86d(2H-C5;9); 7.55d(2H-C2',C5;8.5); 8.0d(2H-C3,C5.;9); 11.12s(2H-OH) De khang dinh them cau tnic ciia san pham chiing tdi da tien hanh ghi phd khdi cua chat vdi hop phan andehit la p-nitro benzandehit (II3) Tren phd khdi chup d dang LC-MS cho th§y pic ion phan tu dang [M+H]^=570 va [M-H]^=568, tu dd suy khdi luang phan tu la 569 va hoan toan phu hpp vdi cdng thuc du doan ma chiing tdi dua Cac pic ion manh cd sd khdi tuang ung deu phii hap vdi sa dd phan manh ciia hop chat du kien Tir cac dii kien phd nhu vay cd thg tin tudng ring cac san pham nhan dupc la diing vdi ciu tao Vdi cac xeton- a,p -khdng no tdng hpp dupc (I, 4), chiing tdi da ti^n hanh thu nghiem hoat tinh khang khuSn doi vdi S.epidermidis (c§u khuin GO, Klebsiella (true khuan Gr") Va nim C.albicans Kk qua cho thiy d ndng dp 0,02 mg/l ml cac xeton- a,p -khdng no ddu cd hoat tinh dang chii y (Bang 4) Banti: Hoat tinh khang khuin va chong nam cua cac xeton- a,p -khong no (I,_4) R,Ar Dirorng kinh vong vo khuan,nim p-Dimetylaminophenyl S.epidermidis (mm) Klebsiella (mm) C.albicans (mm) 13 16 o-Hidroxiphenyl 11 12 14 3,4-Dioximetilenphenyl 16 16 Furyl-2 15 18 (I) THVC NGHIEM Phd hdng ngoai ghi tren may FT-IR 1801 Shimadzu d khoa Hda - Trudng DHKHTN-DHQGHN d dang ep vien vdi KBr Phd ' H-NMR ghi tren may DRX 500 Brucker va phd MS ghi tren may MS-Engine 5989 HP deu d Phdng nghien cuu ciu tnic Vien Hda Hpc- Vien Khoa hpc va Cdng nghe Viet Nam Hpp chit diu 8-axetyl-7-hidroxi-4-metylcumarin dupc tdng hop theo tai lieu [1,2] Hoat tinh sinh hpc dupc thu nghiem d Benh Vien 19-8 ( Bp Cdng An) 1- Phtfong phap chung tong hqrp cac xeton- a,P-khdng no (Ii-4)Dun sdi hdi luu 8-10 gid hdn hpp ciia 0,005 moi 8-axetyl-7-hidroxi-4-metylcumarin vdi 0,005 moi andehit tham tuang iing 30 ml cloroform va vai gipt piperidin lam xiic tac Hdn hop phan ung liic diu tan h^t, sau dd san pham phan ung dupc tao va tach d dang kk tiia dun ndng Lpc hiit lay san pham, nia bang cloroform ndng, de khd ngoai khdng va cd thd ket tinh lai tu etanol Kdt qua dupc gidi thieu d bang 2- Phu'OTig phap chung tdng hpp cac hop chat Hi (San pham phan irng Michael) Dun sdi hdi luu 8-10 gid hdn hop cua 0,01 moi 8-axetyl-7-hidroxi-4metylcumarin vdi 0,005 moi andehit tham tuang ung 30 ml cloroform va vai gipt piperidin lam xiic tac Sau dun ndng mpt thdi gian thiy san phim d d p g kdt tua khdng mau dupc tach ra.Khi phan ung kdt thiic, lpc hiit san phim, nia bang cloroform ndng, dd khd ngoai khdng va cd thd ket tinh lai tir etanol Kdt qua dupc gidi thieu d bang KET LUAN Bang phan iing ngung tu ciia 8-axetyl-7-hidroxi-4-metylcumarin vdi mot sd andehit tham da tdng hop dupc mdt day xeton- a.p -khdng no, ma cau tao va hoat tinh sinh hpc cua chiing da dupc xac dinh Mat khac, cung phan iing nhung tien hanh vdi benzandehit va cac din xuat cd chiia nhdm thd hiit electron ciia nd thi phan ling lai tao cac san pham phan iing kieu Michael Cong trinh ndy duac hodn thdnh vdi su gidp da kinh phi cua De tdi diem QGTD-05-03 cua Dgi hoc Qudc gia Hd ndi TAI LIEU THAM KHAO • 1- V.F.Traven, N.Ya.Podhaluzina, A.V.Vasilyev, A.V.Mamaev, Arkivoe, Vol.1, part 6, html, 931- 938 (2000) 2- Nguyen Minh Thao, Pham Van Phong, Nguyen Xuan Tu, proceeding of Eurasion conference on chemical Science ( EuAs C2S-8), October 21 nd Ha Noi- Viet Nam, Session of Org Chemisfry, pp 15-20 (2003).^ 3- Nguyin Minh Thao, Pham Van Phong, Dd Duy Thing, Nguyin Xuan Tii, tap chi Hda Hpc, T.43, sd 3, tr 326- 330 ( 2005) SCIENTIFIC PROJECT BRANCH: CHEMISTRY PROJECT CATEGORY: main point project of Vietnam National University Hanoi (VNU) 1- Tittle: Study on synthesis, biological activities (antibacterial, anti inflammatory and anti cancer) and practical application of some a, p-unsaturated ketones containing heterocyclic nuclei: indole, furan, coumarin, quinoline 2- Code: QGTD-05-03 3456- Managing Institution: Vietnam National University Hanoi (VNU) Implementing Institution: College of Natural Science, Collaborating Institution: Coordinator: Prof.Dr.Sc Nguyen Minh Thao 7- Key implementors: Prof.Dr.Sc Nguyen Minh Thao Assoc.Prof.Dr Nguyen Dinh Thanh Assoc.Prof.Dr Tran Cong Yen Dr.Luu Van Chinh Master Pham Van Phong Master Nguyen Thi Minh Thu Master Tran Van Tinh Technician Le Thi Minh Nguyet Some Ph.D., Masters and students Director implementors implementors implementors implementors implementors implementors implementors 8- Duration: From June 2005 to June 2007 p9- Budget: 300 millions VND 10- Main results: ^Result in science and technology: - Some hydroxymethoxyacetophenones such as 8-acetyl-7-hydroxy-4-methyl coumarin; 6-acetyl-5 (or 7)-hydroxy-4-methyl coumarin; some 3-acetyl coumarin and some quinolin-2-one derivatives: 6-acetyl-7-hydroxy-4-methyl qumoIin-2-one; 3-acetyl-4-hydroxy-N-phenyl compounds) were synthesized as precursors quinolin-2-one (11 A senes of some a,p-unsaturaled ketones containing heterocyclic nuclei (indole, furan, coumarin and quinoline) were synthesized via QaisenSchmidt condensed reaction of the methyl ketone precursors with aromatic aldehydes (84 compounds) - Strutures os these compounds were elucidated by using IR, NMR and MS data - All synthesized a,p-unsaturated ketones have antibacterial, anti fungi activities and especially, there is a copound which has a remarkble anti cancer activity to lung and lirer cancer cells - Furthermore, some intermediates and unexpected compounds found in the experimental processes were used as eridences (to support) for proposal mechanism reactions *Result in practical application - Almostall synthesized compounds have antibacterial, anti fungi, anti inflammatory activities Especially, there is a copound: (4-hydroxy-lphenylquinoline-2-one-3-yl)(p-nitrophenyl)vinyl ketone which has anti cancer activity to lung and liver cancer cells in vitro and in vivo This result leads to a huge promised practical application ^Result in training: - These is a Ph.D student researching in this project (The project's director is a co-supervisor for the Ph.D student Vu Minh Tan) - There ware four graduated MS and there are three more M.S students who will graduate at the end 2007 - Thirteen chemistry B.S were trained from this project *Publicaions: - Eight research papers have been published 11 Evaluation grade: PHIEU DANG KY KET QUA NGHIEN CUtJ KHOA HOC - CONG NGHE Ten de tai: ''Nghien cuu tong hgp, hoat tinh sinh hpc (khdng khuan, chong viem vd chong ung thu) vd khd ndng ung dung cua mpt so xeton a, fi-khong no cd chura nhan di vdng: indol, furan, cumarin, quinolin" MSL so: QGTD.05.03 Co quan chii tri de tai: Truomg DHKHTN Dia chi: 334 - Nguyin Trai, Thanh Xuan, Ha Ndi Tel: 8588579 Ca quan quan ly de tai: Dai hoc Quoc gia Ha ndi Dia chi: 144, Xuan Thuy, Ciu giiy, Ha Ndi Tel: 8340564 ^ Tong kinh phi thuc chi: 300 tri^u dong Trong dd: - Tu ngan sach nha nudc: 300 trieu ddng - Kinh phi ciia Truomg: - Vay tin dung: - Vdn tu cd: - Thu hdi: Thdi gian nghien cihi: 24 thang Thod gian bat dau: 6/2005 Thai gian ket thiic: 6/2007 Ten cac can bo phoi hop nghien cihi: - PGS.TS.Nguyen Dinh Thanh-Khoa Hoa hoc -Truomg DHKHTN-DHQG Ha Npi - PGS.TS Trin Cdng Yen - Khoa Sinh hpc -Truomg DHKHTN-DHQG Ha Noi - TS Luu Van Chinh - Vien Khoa hoc va Cdng nghe Viet Nam - ThS Pham Van Phong - Khoa Hoa hpc - Truomg DHKHTN-DHQG Ha Npi - ThS Nguyen Thi Minh Thu - Khoa Hoa hoc-Trudmg DHKHTN-DHQG Ha Noi - ThS Trin Van Tinh - Benh vien 19-8 - Bd Cdng an - KTV Le Thi Minh Nguyet - Khoa Hoa hpc - Truang DHKHTN-DHQG Ha Npi, - Mdt so NCS, HVCH va sinh vien Sd chiing nhan dang ky ket Bao mat: a.Phd bien rong rai: x qua nghien ciiu: b.Phd bien han che: c.Bao mat: ket qua nghien cuu: , , , Da tdng hprp dugc 11 hop chat loai metylxeton dung de lam chat dau Da tdng hop duac 84 hop chat mai thupc loai xeton a,p-kh6ng no ma phan tii ciia chiing cd chiia cac nhan di vong nhu indol, furan, cumarin, quinolin Hau hdt cac xeton a,P-khdng no deu cd hoat tinh khang khuan va chong Sd dang ky de tai Ngay: Tom tat - - nam Mdt sd c6 kha nang khang cac chiing loai khuan gay mii xanh nen cd hoat tinh chong viem nhilm Dac biet cd mot hop chit cd kha nang chong ung thu gan va phoi ca in vitro va in vivo - Ngoai cac xeton a,p-khdng no da phat hien duac mdt sd san phim khdng binh thudmg khac Da lam sang ro chidu hudng va ca chd tao chiing - Da^xac dinh cau tao ciia cac hop chit tong hep duprc nhd phd hong ngoai, cdng huomg tu proton va phd khdi lugng - Da dao tao dugc thac sT va 13 cii nhan hda hgc Mdt sd hpc vien cao hpc se bao ve luan van thac sT vao cudi nam 2007 - Da cdng bd bai bao khoa hoc lien quan tori kit qua thuc hien dl tai Kien nghj ve cjuy mo va doi tugng ap dung nghien ciru: Neu cd dieu kien xin dugc cip them kinh phi dl nghien ciiu them kha nang chong ung thu va kha nang ung dung ciia hgp chit da biet cung nhu mot sd hgp chat khac tdng hgp dugc Chii nhiem de Thii truomg co Chii tich Hdi Thii truang ca quan chii tri de ddng danh gia quan quan ly tai tai chinh thiic de tai Nguyen Minh Ho ten Tmh ll^t Scm Mi