Tổng hợp dẫn xuất của 2 deoxy glucose

1 TC GI: Nguyn Thanh Tõm TểM TT Lnh vc húa-dc phm l mt lnh vc nghiờn cu ng dng húa hc vo ngnh dc phm, úng vai trũ vụ cựng quan trng cuc sng Trờn th gii, cỏc nh khoa hc, nghiờn cu, phỏt minh ó tỡm tũi, sỏng to khụng ngng cho i nhiu sn phm mang li li ớch v sc khe th cht cho ngi, cng nh gúp phn rt ln vo s phỏt trin ca khoa hc k thut nhm mc tiờu bo m cho ngi cú cuc sng khe mnh, th gii ngy cng phỏt trin i theo ng ú, tụi tin hnh nghiờn cu v vic tng hp cỏc dn xut ca 2- deoxy-glucose, l mt h cỏc hp cht c cho rng cú hot tớnh chng ung th õy l ó c nghiờn cu nhiu trờn th gii t cỏch õy nhiu nm, nhiờn cũn khỏ mi m Vit Nam Trong quỏ trỡnh thc hin nghiờn cu, tụi ó thc hin cỏc phn ng tng hp hu c, cú ỏp dng cỏc phng phỏp cụ lp v lm tinh sch hp cht hu c: phn ng cng hp nc, phn ng methanolysis, v thc hin vi cỏc t l v lng cht khỏc nhm ti u húa v tng hp thnh cụng Kt qu t c l tụi ó tng hp c hp cht l-(furan-2-yl)-2-(trityloxy)ethanol m theo mt s ti liu tham kho cho thy nú cú kh nng khỏng nm v t bo ung th Tuy ó ht sc c gng hon thnh nhim v t ra, nhng tụi cũn gp mt s khú khn khỏch quan, vỡ th cú th kt qu nghiờn cu cha tht s tt Tụi rt mong nhn c s hng dn, ch bo cng nh phờ bỡnh ca Ban giỏm kho CHNG TNG QUAN 1.1 Tng quan v glucose vD-glucal 1.1.1 Glucose Glucose, mt monosaccharide (hay ng n), l mt carbohydrate quan trng sinh hc Cỏc t bo sng s dng nú nh mt ngun nng lng v trung gian cho s trao i cht Glucose l mt nhng sn phm chớnh ca phn ng quang hp v bt u quỏ trỡnh hụ hp ca t bo c sinh vt cha cú nhõn in hỡnh v eukaryote Tờn glucose bt ngun t ting Hy Lp glykys (ý), cú ngha l ngt, tip v ng -ose bao hm ý mt loi ng Hai ng phõn lp th ca ng aldohexose l glucose, ú ch cú D-glucose l cú hot tớnh sinh hc Dng ny thng c cp ti vi tờn dextrose monohydrate, hoc l dextrose cụng nghip thc phm Glucose Glucose cú lng phõn t 180.16 g moi"1, lng riờng 1.54 g cm"3 Nhit núng chy a-D-glucose - 146c, b-D-glucose - 150c ng aldohexose cú bn tõm th tớnh cho 24 = 16 ng phõn lp th Cỏc ng phõn ny c chia thnh hai nhúm, L v D, mi nhúm cú tỏm loi ng Glucose l mt nhng ng ny, v L v D l hai s cỏc ng phõn lp th Ch cú by s nhng loi ny c tỡm thy c th sng, ú D-glucose, D- galactose v D-mannose l quan trng nht Tỏm ng phõn ny u l ng phõn xuyờn lp th ca v u thuc nhúm cỏc ng dng D- Trong ni dung ca lun ny, ngi vit ch xin núi ti dng D-glucose (ngoi cũn dng L-glucose, khụng th c chuyn húa bi t bo hay gi l s ng phõn) Glucose (C6H1206) Cể sỏu nguyờn t carbún, mt s ú l ca nhúm aldehyde, ú c cp n nh l mt aldohexose Trong dung dch, phõn t glucose cú th tn ti dng mch h hoc mch vũng (vi t l bng nhau) Tuy nhiờn, pH thỡ dng mch vũng chim u th hn th rn, glucose cú dng vũng Vỡ dng mch vũng cha nm nguyờn t carbon v mt nguyờn t oxy, tng t vi cu trỳc ca pyran nờn nú cng c xem l glucopyranose Trong vũng ny, mi nguyờn t carbon ni vi mt nhúm hydroxyl, ngoi tr nguyờn t carbon th nm l ni vi nguyờn t carbon th sỏu ngoi vũng, to thnh nhúm CH2OH Glucose thng tụn ti dng khụi trng hoc nhng thờ rn Ngoi nú cng cú thờ tụn ti dng dung dch vi nc - MnH i V Un OH OH O èH ềH Cụng thc Fischer ca D-gucose mch h Dng mch thng ca D-glucose a-D-glucopyranose b -D-glucopyranose Trong t nhiờn, glucose l sn phm chớnh ca phn ng quang hp cõy c v mt s sinh vt cha cú nhõn in hỡnh cỏc loi ng vt v cỏc loi nm, glucose l sn phm ca s phõn hy glycogen (glycogenolysis) Ngoi ra, ng vt, glucose c tng hp gan v thn t cỏc cht trung gian khụng phi carbohydrate nh pyruvate v glycerol (gluconeogenesis) Glucose gp nhiu trỏi nho chớn, cỏc loi trỏi cõy chớn khỏc, cng nh mt ong Trong thng mi, glucose c sn xut thụng qua quỏ trỡnh thy phõn tinh bt cú s tham gia ca enzyme Glucose dng bỏnh Glucose 1.1.2 D-glucal D-glucal tờn y l 3,4,6-tri-O-acetyl-D-glucal (D-glucal triacetate) cú cụng thc phõn t l C12H1607, lung mol phõn t l 272.25, nhit núng chy l 51 - 53c, 3,4,6-tri--acetyl- D-glucal cú dng tinh th, mu trng, cụng thc cu to dng sau: hay o ú Ac l nhúm CH3CO- Xột v nh hng n th cht, D-glucal c xp vo loi an ton (safe) Vic gn cỏc nhúm th vo hp cht ny c cho l mang li cỏc sn phm cú hot tớnh sinh hc, dc hc v tip tc c th nghim II Cỏc nghiờn cu v D-glucal Vit Nam, tớnh n chỳng ta cha cú nhiu nghiờn cu sõu v D-glucal v cỏc dn xut ca nú Tuy nhiờn, trờn th gii, vic i sõu nghiờn cu tỡm hiu v cu to, tớnh cht, hot tớnh nht l dc tớnh ca chỳng ó bt u t rt lõu v hin cụng vic ny tip din ó cú rt nhiu bi bỏo cỏo khoa hc trờn cỏc t bỏo, uy tớn trờn th gii v cỏc hp cht ny T nm 1985, ngi ta ó nghiờn cu tng hp nhiu hp cht cú hot tớnh sinh hc ỏng lu ý Mt bỏo cỏo ngy 16 thỏng nm 1985 ca cỏc tỏc gi: Yi-Guo Zhou, Chyng-Yann Shiue, Alfred p Wolf, v Carroll D Arnett (Department of Chemistry, Brookhaven National Laboratory, Upton, New York 11973, USA) c óng trờn European Journal of Nuclear Medicine Bỏo cỏo ny núi v s tng hp 2-deoxy-2- [82Br]bromo-D-mannose (4b) v cỏc hp cht liờn quan (vớ d 2-deoxy-2-[82Br]bromo- 3,4,6-i--acetyl-a-D-mannopyranosyl chloride (3b) v s phõn b sinh hc ca chỳng trờn chut Trong nghiờn cu ny, phn ng gia 3,4,6-tri-O-acetyl-D-glucal (TAG2) vi bromine chloride unlabeled v labeled (la, lb) ni sinh t s oxy húa bromide vi N-chlorosuccinimide cho 2-deoxy-2-bromo-3,4,6-tri--acetyl-a-D- mannopyranosyl chloride unlỏbeled v labeled (3 a, 3b) vi hiu sut húa hc phúng x l 58% (hiu sut húa hc, 63%) S thy phõn 3a, 3b vi 2N HC1 cho 2-deoxy-2- bromo-D-mannose (4a, 4b) vi hiu sut húa hc phúng x l 72% Sau tiờm 3b v 4b lờn c th chut, kt qu cho thy 2% tớnh phúng x trung nóo, 6% tim; nhiờn tớnh phúng x trờn hai c quan ny st gim sau 15 Phn ng xy l: la,fc Ja, h 4i,b & - fc b* Fig, I Symeõs oớ 2(k!H^2^BfbtK)tmớHớaanncse from ,2Br-labcte3 ngm nc) to thnh 1,2- anhydrosugars vi hiu sut 99% v chn lc 100% Tng t, vi 3,4,6 -tri-O- acetyl-D-glucal s cho kt qu l mt hn hp dn xut gluco v manno, t l 7:1, hiu sut 87%.[9] Cỏc phn ng xy l: Ctoon* acetoneaq NftHCQj CHfClg c ta It, h t CttjQH rt h (00%) S (S#%) H*^O0n 0*c CS3ằj ĂHI 1,2,3; R' =n R7 = H gnflte4 5, ô: R1 A H fl2 BOBTI Nctn- Bh- I Ose atwlcra -K aq NEHCOJ, CHjCij Q c to n &5 h ô% 'Hrfcwriii' Ngoi ra, cũn cú cỏc nghiờn cu khỏc ca cỏc nh nghiờn cu nhiu ni trờn th gii v lnh vc ny nh quỏ trỡnh tng hp morphine t D-glucal, tng hp dn xut ca 2-fluoroglucal [20], [11], [15], [16] Núi chung õy l mt lnh vc nhn c nhiu s quan tõm ca gii khoa hc trờn ng tỡm nhng phng thc mi iu tr cỏc cn bnh ung th, khỏng nm 13 F l furandiol Phn ng ny ta thc hin pH ban u l - 4, s dng khong HgS04 vi mt lng khong 5% lng D Phn ng c thc hin mụi trng nc hũa tan HgS04 Ta theo dừi tin trỡnh phn ng bng TLC, h dung mụi gii ly l ethyl aceate : cyclo hexane 1:3 Sau phn ng, ta cng trung hũa bng NaHC03 10% Ta chit dung dch thu c vi ethyl acetate, nhng ln ny ta thu lp nc vỡ kt qu TLC cho thy cht cn tỏch nm lp nc Tin hnh cụ quay, ri pha loóng dung dch m c thu c vi dichloromethane np mu lng lờn ct (ch yu loi bt HgS04 cũn li v cỏc cht bn) 2.4 Phn ng tng hp dn xut ca 2-deoxv-glucose Sau ta thu c F, ta tip tc thc hin phnphn ng ng sau: sau: z hin ml CH2C12 eq TrCl V 0.1-0.2 ml EtgN OH OH CVi/-\ o G TrCl l triphenylmethyl chloride Et3N l triethyl amin (C2H5)3N Phn ng c theo dừi bng TLC vi h ethyl acetate : cyclo hexane 1:1 Sau phn ng, ta chit dung dch thu c vi ethyl acetate, thu lp ethyl acetate, lm khan vi Na2S04 khan, cụ quay ri li hũa tan mu, np lờn ct tin hnh tỏch ly G G l l-(furan-2-yl)2-(trityloxy)ethanol, mt dn xut ca 2-deoxy-glucose 14 CHNG KT QU V BN LUN * Xột vhn ns cụns hV nc (l) (xỳc tỏc HBr) vi cỏc t l dung mụi nh ó chn, ta nhn thy rng: - Phn ng xy chm S lng cht trung gian/b phõn hy nhiu (ngay c tỏc cht cũn vi nng cao) Thi gian lng cht trung gian/b phõn hy xut hin nghch bin vi nng HBr dung dch phn ng, tc l: cng dựng lng d HBr, thi gian cỏc cht trung gian/b phõn hy sinh cng ngn vi lng cng cao Nng cỏc cht trung gian/b phõn hy so vi cht cn tỏch l xp x Ta cú hỡnh dng ca cỏc bn sc ký theo dừi tin trỡnh nh sau: Acid HBr 5M: T l mol 1:4 + Sau gi + Sau gi + Sau gi + Sau gi + Sau 1.5 gi T l mol 1:10 + Sau 0.5 gi + Sau gi 15 Acid HBr 1M: T lờ mol 1:1 + Sau gi T l mol 1:2 + Sau gi T l mol 1:4 + Sau 0.5 gi + Sau gi + Sau 1.5 gi + Sau 2.5 gi + Sau 4h ỡ + Sau gi I + Sau gi + Sau gi 16 T l mol 1:10 + Sau 0.5 gi + Sau gi + Sau gi + Sau 2.5 gi + Sau 1.5 gi + Sau gi n + Sau 3.5 gi + Sau gi Vy qua ú ta a kt lun rng: Phn ng xy cú th i kốm cỏc phn ng ph hoc, - HBr va úng vai trũ xỳc tỏc va úng vai trũ tỏc cht, s lm phõn hy cỏc cht va c to thnh hoc, Cú s sinh ca cỏc sn phm ph lm c ch phn ng chớnh, ng thi lm cho phn ng ang xy i theo mt hng khỏc, to nờn cỏc sn phm khỏc Vỡ th ta khụng th tin hnh tỏch sn phm mong mun mt cỏch d dng v hiu qu c Hiu sut phn ng khụng cao Xột thy phn ng (1) khụng cho kt qu nh mong mun, ta thay i cht xỳc tỏc s dng T acid HBr, ta chuyn sang s dng acid H2S04 * Xột phn ns (3) tng t nh phn ng (1), ta cú cỏc kt qu TLC nh sau: 17 T l mol 1:1 + Sau 0.5 gi + Sau gi + Sau 1.5 gi + Sau 2.5 gi + Sau 3.5 gi + Sau 4.5 gi + Sau gi + Sau 4.5 gi I + Sau 5.5 gi T l mol 1:2 + Sau 1.5 gi 18 T l mol 1:4 + Sau 0.5 gi + Sau gi + Sau 1.5 gi 111 + Sau gi t T l mol 1:8 + Sau 0.5 gi + Sau gi + Sau 1.5 gi ; I1 + Sau gi T l mol 1:10 + Sau 0.5 gi h + Sau gi + Sau 1.5 gi + Sau gi 19 + Sau 2.5 gi + Sau gi T l mol 1:16 + Sau 1.5 gi Qua cỏc hỡnh nh TLC thu c, ta cú th a cỏc nhn xột rng: Tuy tc phn ng thp nhng lng cht trung gian/b phõn hy ớt hn so vi phn ng (1) - Dự vy, lng cht trung gian/b phõn hy l ỏng k Nng cỏc cht trung gian/b phõn hy l xp x - Vỡ th ta khụng th tin hnh tỏch sn phm mong mun mt cỏch d dng v hiu qu c Vy, thụng qua phn ng (1) v (3), ta kt lun chung rng: Phn ng cng hp nc ca (-)-tri-O-acetyl-D-glucal vi xỳc tỏc H+ ( phm vi lun vón ny, ta ch xột acid HBr v H2S04) cho hiu sut khụng cao, lng sn phm ph nhiu, cú nng tng i dung dch l cao Do ú, ta rt khú tỏch ly cht mong mun mt cỏch hiu qu c Hiu sut phn ng cc kỡ thp 20 Do tớnh kinh t, ng dng v hiu qu cn t c, ta tin hnh tng hp dn xut ca 2deoxy-glucose theo mt hng khỏc * Xột phn ne methanolysis: Ta thy rng, phn ng (4): Xy nhanh - ớt sn phm ph - Cú th tỏch ly sn phm chớnh khỏ hiu qu Kột qu TLC: + Sau gi + Sau gi Tuy nhiờn, em D (sn phm chớnh ca (4)) tip tc lm tỏc cht (5) (phn ng cng hp nc) tng hp E, ta thy (5) cho kt qu l: - Nhiu sn phm khụng mong mun vi nng tng i hn hp cao Rt khú tỏch ly E mt cỏch hiu qu + Sau 0.5 gi + Sau gi + Sau 1.5 gi Vy ta s khụng tip tc phn ng (5) Sau tỏch ly D (4), ta cho D phn ng vi H2S04/HgS04, phn ng (6) Lu ý: Methanol (MeOH) l cht c, cú th nh hng n h thn kinh, gõy mự mt v dn n t vong nu ta tip xỳc khụng cn thn (hớt, dớnh vo da v thm qua da, ) vi lng vi ml * Xột phn ng (6): Phn ng ny cng cho kt qu tng i tt, tc l: Thi gian phn ng tng i ngn 21 ớt sn phm ph Cú th tỏch ly F tip tc cho phn ng sau Kt qu TLC sau gi: Tuy nhiờn, cn chỳ ý rng HgS04 l cht c, ta phi cn thn tip xỳc * Xột phn ne (7): Phn ng xy tng i nhanh, ớt sn phm ph, cú th tỏch c bng sc ký ct Sau phn ng, ta chit dung dch thu c vi lp ethyl acetate, ly lp ethyl acetate, lm khan, em cụ quay, hũa tan mu vi dichloromethane ri ta tin hnh tỏch ly G bng ct sc ký Ph H-NMR ca G DANH-TTD.Tam-CDC13-1H -% 'J a n r- * *> n r- H n 1ằ ằ n a ri "! rt H I- H D -ằ r- r- r, o -r J ằ a r p ằ rI J D o rỡ c* o ' rt rIp II ớl I 111 n M I1ô n q I' rt n r rt ^ rt r rt n I | M a * II u J ằ T r f T T ằ rt n rt |\ nằ ft IJ ẫf ft * h r t- r * f* uô tmc 3*1* t; lôUM_rrx :* r: JhenintlM fi:wuc Tuằ TKTIW mo Kifớo< n Xjlibfl K M m r=*xi *3 kj M tc Tt II icmr PMM Vl ôô*# MI tr ằ-;1 S?M 43U4 C 14 HIM.3M M I.5SSM * i.Si iil.l H.JN u (J V lji.i K .IIUMM M & 11WCGM u RJ*X rr,^ r JACU Ti ằa PL m iru r- - 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M K SH c.u ô L.N 1?ằ m lỡ# imk H rrrrr n ĂP 11 +1 ằ 41 SM.LHSS3 H 22 DAHH-TTP.Tam-CpCl3-1H s K aủilas-: bri F) rt rn r*! 3RằS * fi& a*ô 4 Hằ j 'j J -i ằHằ j -ằ r rO Aằ"- ô5ô r Pr35SSẽ"i! # **1 ri ô ri P- y I'' ' I .3 ó.S I' 5S - - 5.0 ! I' 4.-5 ' 1 T" ô.0 I J1 3.ẻ PPđ L; J.' ? ô> C3 3; ri w DANH-TTD Twn-CDCl 3-1H S M H SU ri rt ri sằi|*32BEgaaÊ2:aÊÊS3S:!SL2sa35!:?s ii^saapiii^sxiSBSissgar?-* n C '4 ằmit ^ r r I' J* r iiiJằ diTT*i*in * (ri ri *i rs ri ô I PI M n ri -4 r4 ằ1 H rrnrớ-* ri -4 r-1 H T ợ n H ri H riH r-s -1 11-1 n n P -1 Tri r-? I * O fci ằ- I n r n r I ri rt T- ri 23 Sau kho sỏt cỏc phn ng trờn vi nhiu lng tỏc cht khỏc nhau, ta thc hin quỏ trỡnh tng hp G vi tỏc cht ban u l g (-)-Tri-O-acetyl-D-glucal, sau nhiu giai on phn ng kt thỳc - chit - lm khan - cụ quay - sc ký ct, ta thu c 0.006 g Hiu sut ca ton quỏ trỡnh l 0.6%! Ta nhn thy rng, hiu sut ton quỏ trỡnh rt thp, nguyờn nhõn l do: - Hiu sut mi phn ng < 100% - Phn ng cú cỏc sn phm ph m ta khụng thu nhn Lng mu cht b hao ht cỏc quỏ trỡnh chit (cú cỏc cht tan lp cũn li m ta khụng thu nhn), lm khan (cht cũn dớnh li trờn Na2S04), cụ quay (mt phn b lụi cun theo dung mụi), sc ký ct (mi ln sc ký ct lng mu cht theo thng kờ b hao ht khong 30%), hn na ta ch thu nhn cht ta mong mun, khụng nhn cỏc cht cũn li Ta cú th kt lun rng: quỏ trỡnh l ni tip v xy qua quỏ nhiu giai on, cú s xut hin ca sn phm ph, mi giai on cn cỏc bc lm tinh sch nờn khú trỏnh b hao ht Hn na, iu kin v húa cht (khụng mua c, giỏ cao, c hi, ) dng c thớ nghim, iu kin tin hnh thớ nghim, thi gian ta khú cú th kho sỏt trờn mt lng ln tỏc cht thu c kt qu cao hn Mun tng hiu sut tng ca quỏ trỡnh, ta cn nghiờn cu sõu hn, cú th thay th nhiu giai on bng mt giai on no ú tng ng gim bt hao ht, i sõu vo kho sỏt chi tit cỏc iu kin khỏc nh nhit , ỏp sut, , thc hin trờn lng tỏc cht, xỳc tỏc thay i t nh n ln, khong rng, thu c nhiu thụng tin cú th nm bt tt hn y hn v quỏ trỡnh, t ú lm tng hiu sut tng 24 TI LIU THAM KHO [1] Nguyn Kim Phi Phng, Phng phỏp cụ lp hp cht hu c, Nh Xut bn i hc Quc gia thnh ph H Chớ Minh, Thnh ph H Chớ Minh, Vit Nam, 2007 [2] Phan Thanh Sn Nam, Bi ging húa hu c, 2007 [3] Yi-Guo Zhou, Chyng-Yann Shiue, Alfred p Wolf, v Carroll D Arnett, Synthesis of 2-deoxy2-[82Br]bromo-D-mannose and related compounds and their bio distributions in mice , Department of Chemistry, Brookhaven National Laboratory, Upton, New York 11973, USA, 1985 [4] Daley, Pierre Demerseman, Claude Monneret (UMR 176 CNRS/Institut Curie, Section Recherche, Paris), Yves Guminski, Chantal Etiộvant, Thierry Imbert (Pierre Fabre Medicament C.R.P.F., Division de Chimie Mộdicinale), Anna Kruczynski v Bridget T Hill (Pierre Fabre Medicament C.R.P.F., Division Cacộrologie Expộrimentale), Synthesis and Antitumor Activity of New Glycosides of Epipodophyllotoxin, Analogues of Etoposide, and NK 611,1998 [5] Corin M Storkey, Anna L Win v John o Hoberg, Synthesis of 2,3,4,6-tetra-O- benzyl-Dglucal on the gram scale A convenient method for its facile synthesis and subsequent stereoselective cyclopropanation, School of Chemical and Physical Sciences, Victoria University of Wellington, PO Box 600, Wellington, New Zealand, 2003 [6] Susheel J Nara, Swapnil s Mohile, Jitendra R Harjani, Prashant u Naik, Manikrao M Salunkhe, Influence of ionic liquids on the rates and regioselectivity of lipase-mediated biotransformations on 3,4,6-tri-O-acetyl-d-glucal, Department of Chemisy, The Institute of Science, 15-Madam Cama Road, Mumbai 400032, India, 2004 [7] Antonella Squarcia, Simona Marroni, Giovanni Piancatelli and Pietro Passacantilli, Glycalmediated syntheses of enantiomerically pure 3-azido-2,3-dideoxy- hexopyranosides and 3-amino2,3-dideoxy-hexopyranolactones, Dipartimento di Chimica and Istituto di Chimica Biomolecolare del CNR, Sezione di Roma, Universita' La Sapienza, Piazzale Aldo Moro 5, 00185 Roma, Italy, 2004 25 [8] Christophe Morin, Procurement of 2-deoxy-2-iodo-D-glucose (2-DIG), Laboratoire dEtudes Dynamiques et Structurales de la Se" lectivite' (LEDSS), UMR 5616 (IFR 2607), Universitộ" Joseph Fourier Grenoble 1, 38402 St Martin dHe'res, France, 2006 [9] Pavel Cheshev, Alberto Marra and Alessandro Dondoni, Direct epoxidation of D- glucal and D-galactal derivatives with in situ generated DMDO, Laboratorio di Chimica Orgỏnica, Dipartimento di Chimica, Universita' , di Ferrara, Via L Borsari 46,1-44100 Ferrara, Italy, 2006 [10] Ewan Boyd,a Michael R Hallett,b Ray V H Jones,a James E Painter,b Prakash Patel,c Peter Quayleb, and Anita J Waring (ne'e Potts)b, The lithiation of 2- chloroglucal derivatives, aSyngenta,Grangemouth Manufacturing Centre, Earls Road, Grangemouth FX3 8XG, Scotland, UK bSchool of Chemistry, University of Manchester, Manchester Ml3 9PL, UK cAvecia Inkjet Ltd., Hexagon Tower, Blackley, Manchester M9 8ZS, UK, 2006 [11] Ewan Boyd,a Ray V H Jones,a Peter Quayleb, and Anita J Waring (ne'e Potts)b, A synthesis of 2-fluorogiucai derivatives, aSyngenta, Grangemouth Manufacturing Centre, Earls Road, Grangemouth FX3 8XG, Scotland, UK bSchool of Chemistry, University of Manchester, Manchester M13 9PL, UK, 2006 [12] Dominique Lafont and Paul Boullanger, Syntheses of L-glucosamine donors for 1,2-transglycosylation reactions, Universitộ' de Lyon, France; Chimie Physique Electronique de Lyon, Laboratoire de Chimie Organique II-Glycochimie, CNRS UMR 5181, Universitộ Lyon 1, 43 boulevard du 11 Novembre 1918, F-69622 Villeurbanne Cedex, France, 2007 [13] Xiang-Bao Meng,a Dong Han,a Su-Na Zhang,a Wei Guo,b Jing-Rong Cuib and Zhong-Jun Lia,b, Synthesis and anti-inflammatory activity of Nphthalimidomethyl 2,3-dideoxy- and 2,3-unsaturated glycosides, aDepartment of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China bNational Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083, China, 2007 [14] Carlos Mayato, Rosa L Dorta and Jesu's T Va'zquez, The exo-deoxoanomeric effect in the conformational preferences of C-glycosides, Instituto Universitario de 26 Bio-Orga' nica Antonio Gonza' lez, Departamento de Quý'mớe a Orga' nica, Universidad de La Laguna, 38206 La Laguna, Tenerife, Spain, 2007 [15] Qi Chen and Yuguo Du, Synthesis of sporiolide B from D-glucal, State Key Laboratory of Environmental Chemisy and Ecotoxicology, Research Center for Eco - Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China, 2007 [16] Achim Benz, Stefan Immel and Frieder w Lichtenthaler, On the alkoxybromination of glucal esters: 2-acetamido-a-D-mannosyl bromides from 2- acetamidoglucal, Clemens-Scho" pfInstitut fu" r Organische Chemie und Biochemie, Technische Universita" t Darmstadt, D-64287 Darmstadt, Germany, 2007 [17] Am'elia p Rauter a,, Fania Almeida a, Nuno M Xavier a, Filipa Siopa a, Ana I Vicente a, Susana D Lucas a, Jo~ao p Marques b, Fernando RanToa Ribeiro b, Michel Guisnet b, Maria J Ferreira c, Acid zeolites as efficient catalysts for O- and S- glycosylation , a Departamento de Qu'ymica e Bioqu'ymica/Centro de Qu"ýmica e Bioqu'ymica, Faculdade de Ci'encias da Universidade de Lisboa, Ed C8, 5o Piso, 1749-016 Lisboa, Portugal b Centro de Engenharia Bio Logic a e Qu'ymica, Instituto Superior Fecnico, Av Rovisco Pais, 1049-001 Lisboa, Portugal c Centro de Qu'ymica Estrutural, Instituto Superior Fecnico, Av Rovisco Pais, 1049-001 Lisboa, Portugal, 2007 [18] Marta Teijeira, Yagamare Fall, Francisco Santamarớa and Emilia Tojo, Efficient and rapid experimental procedure for the synthesis offuran diolfrom D-glucal using ionic liquid, Departamento de Quý "mica Orga" nica, Facultad de Quý "mica, Universidad de Vigo, 36200 Vigo, Spain, 2007 [19] Carlos Mayato, Rosa L Dorta and Jesu"s T Va"zquez, New insights into the conformational properties of a-C-glucosides, Instituto Universitario de Bio-Orga" nica Antonio Gonza' lez, Departamento de Quý mica Orga' nica, Universidad de La Laguna, 38206 La Laguna, Tenerife, Spain, 2007 [20] Hiroki Tanimoto, Ryosuke Salto and Noritaka Chida, Formal synthesis of (fimo r phin e from D-glucal based on the cascade Claisen rearrangement, Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan, 2007 27 [21] J S Yadav, B V S Reddy, K Bhaskar Reddy, M Satyanarayana, CeCl3.7H20: a novel reagent for the synthesis of -deoxy sugars from D-glycals, Tetrahedron Letters 43, 7009-7012, 2002 [22] Francesco Gonzalez, Suzanne Lesage, Arthur S Perlin, Catalysis by mercuric ion of reactions of glycals with water, Carbohydrate Research 42, 267-274, 1975 [23] Adriano A Mendes, Dasciana S Rodrigues, Marco Filice, Roberto Fernandez- Lafuente, Jose M Guisan, Jose M Palomo, Regioselective monohydrolysis of per-O- acetylated-lsubstituted-B-glucopyranosides catalyzed by immobilized lipases, Tetrahedron 64, 1072110727,2008 [24] Anna W Pierwocha, Krzysztof Walczak, The use of tri-O-acetyl-D-glucal and - D-galactal in the synthesis of w-aminoalkyl 2-deoxy- and 2,3-dideoxy- Dhexopyranosides , Carbohydrate Research 343, 2680-2686, 2008 ... ).7(l,H Cl n.7 U8a.7 3..3 2. ft 2, 910 2. 210 .2 2.1 0.1 L.7,9 i ớ) 1.9 0.7 1.4x0 1.2l>-5 5+9,9 17+9.6 2. ô 0 .2 .7 0 .2 04 0.1 1.510.6 1.010.4 0,3 0 .2 24.1 5.4 I.J to? II2 2, 7 3.71 ? 0.5 lOi Percenrliige... 4 .2 I4.IM.3J' 3.3 3.1-3.51 5.1 4.7 5.4} 4 .2 p.h 4.6} 4 .2 1' 4.4} 41 ớ* 2- 9.0) 4.1 (4J0-4.3) 2- 2 (2. 1 -2 0.9(06-t.O) 3) 6.6 (5.4-7.4) 60min L (1.7-1.9) 15(1.3-1.6) 13(11 2. 4) ll (lo J) I 9;J-2J8)... Hiyoshi, Kohoku-ku, Yokohama 22 3-8 522 , Japan, 20 07 27 [21 ] J S Yadav, B V S Reddy, K Bhaskar Reddy, M Satyanarayana, CeCl3.7H20: a novel reagent for the synthesis of -deoxy sugars from D-glycals,