Tetrahedron: Asymmetry

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1 Tetrhedron: Asymmetry 20 (2009) Contents lists ville t Sieneiret Tetrhedron: Asymmetry journl homepge: A onvenient ess to the 1,5-nhydro forms of -tgtose, L-rhmnulose nd -xylulose vi 2-hydroxyglyl esters q Pn Jrglis, Volker Gökel, Frieder W. Lihtenthler * Clemens-Shöpf-Institut für rgnishe Chemie und Biohemie, Tehnishe Universität rmstdt, rmstdt, Germny rtile info strt Artile history: Reeived 26 Ferury 2009 Aepted 18 Mrh 2009 Aville online 22 April 2009 Speil edition of Tetrhedron: Asymmetry in honour of Professor George Fleet s 65th irthdy Zemplén methnolysis or three-step protool omprising hydroxylminolysis, de--etyltion nd deoximintion smoothly nd effiiently onvert the enzoylted 2-hydroxy--glyls of -gltose, L- rhmnose nd -xylose into their onfigurtionlly relted 1,5-nhydro-ketoses, therey providing onvenient ess to the 1,5-nhydro forms of -tgtose, L-rhmnulose nd -xylulose. Invrily otined s morphous solids, they re est hrterized through their highly rystlline oximes. Ó 2009 Elsevier Ltd. All rights reserved. 1. Introdution Potentil pplitions of 1,5-nhydro--frutose 1 s powerful ntioxidnt, 2,3 n ntimiroil gent, 2,3 food dditive 3 or phrmeutil 4 hve generted the elortion of series of hemil nd enzymti syntheses, the most onvenient eing the -1,4- glun lyse-indued degrdtion of strh, 5 nd the Zemplén methnolysis of tetr--etyl-2-hydroxy--glul. 1 f other 1,5- nhydro-ketoses, whih re likely to hve similr pplition profiles, only 1,5-nhydro--tgtose 2 hs eome known, either through lorious seven-step hemil proedure strting from -gltose, 6 or y teril oxidtion of 1,5-nhydro--gltitol, 7 whose quisition from -gltose requires four steps. Relying on the methodology developed for the otention of 1,5- nhydro--frutose, 1 we here desrie onvenient proedures for the onversion of -gltose, L-rhmnose nd -xylose into the 1,5-nhydro derivtives of -tgtose 2, L-rhmnulose 3 nd - xylulose 4, respetively. 2. Results nd disussion ,5-Anhydro--tgtose The methodology reently dvned for the strightforwrd liertion of 1,5-nhydro--frutose from 2-hydroxy--glul esters, 1 (diret Zemplén methnolysis or three-step protool involving enol ester hydroxylminolysis, de--yltion nd deoximtion) ould redily e pplied to the -glto nlogue 5 with only minor experimentl dpttions: Exposure to hydroxylmine hydrohloride in pyridine t mient temperture smoothly onverted q Prt 43 of the series Sugr-erived Building Bloks ; for Prt 42, see Ref. 1. * Corresponding uthor. Tel.: E-mil ddress: lihtenthler@hemie.tu-drmstdt.de (F.W. Lihtenthler). 5 into the E-oxime 6 (82%), redily deprotetle y Zemplén methnolysis to 7 (Sheme 1), oth oximes feture useful properties suh s high rystllinity nd ese of isoltion. Their deoximtion with etldehyde/cl either fforded 1,5-nhydro--tgtose 2 or its triette 8 in exellent yields, yet s reveled y 1 nd 13 C NMR dt, oth umulted s mixtures of the keto nd 2,2-dihydroxy (hydrte) forms in rtios vrying etween 5:2 nd 2:1 in fvour of the monohydrtes. This tendeny towrds elortion of the monohydrte forms in the se of lredy previously oserved y Freimund nd Köpper 7 is in distint ontrst to tht of the 4-epimeri 1,5-nhydro--fruto ompounds: the orresponding ulose triette, nlogously prepred y hydroxylminolysis of the 2-hydroxy--glul ester nd susequent deoximtion, ws otined in rystlline form (89%) s the unhydrted ketose, 1 whilst 1,5-nhydro--frutose 1 fully dopts the 2,2-dihydroxy (hydrte) form in queous solution. 1 2 (-fruto) (-tgto) 3 4 (L-rhmnulo) (-xylulo) In the etylted ulose 8, -elimintion of eti id is filitted y the trns-dixil disposition of -3 nd 4-A; thus onversion to the enolone ester 11 lredy ourred on longer ontt /$ - see front mtter Ó 2009 Elsevier Ltd. All rights reserved. doi: /j.tetsy

2 P. Jrglis et l. / Tetrhedron: Asymmetry 20 (2009) A A A A 5 R R R N 6 R = A 7 R = (6) A A A 8 2 A A A 8 2 d e (7) f EtS g R A R SEt 2 h (10) R SEt A 9 R = A i R = Sheme 1. Retions nd onditions: () N 2 Cl/pyridine, 15 h, rt, 82%; () N/, 20 min, rt, 78%; () etldehyde/cl in CN, 6 h, rt, 95%; (d) N/, 2ht 15 C?rt, 84%; (e) etldehyde/cl in CN, 5 h, rt, 83%; (f) EtS (BF 3, 15 min, rt, 61%; (g) NA/etone, 1 h, rt, 91%; (h) CdC 3 /gcl 2 in wter, 30 min, rt, 69%; (i) N/, 3 h, 0 C, 87%. with sili gel or, for preprtive purposes, y riefly stirring with sodium ette in etone. rptliztion ws redily effeted y exposure to ethnethiol/cl to provide 9, whih ould lso e onverted into 1,5-nhydro--tgtose 2 y Zemplén methnolysis to 10 nd susequent desulfuriztion. By fr the most simple genertion of 1,5-nhydro--tgtose, however, proved to e the diret Zemplén methnolysis of the 2-etoxygltl triette 5 whih, when performed t low temperture, proeeded without -elimintion, oviously due to the formtion of the monomethnolte 8 s the first intermedite rther thn the ketose 8 whih under the slightly si Zemplén onditions would redily undergo -elimintion to enolone ,5-Anhydro-L-rhmnulose Being redily essile in four-step, lrge sle-dptle protool from L-rhmnose, 8 the 2-enzoyloxy-L-rhmnl dienzote 12 ws similrly sujeted to Zemplén methnolysis whih proved to e somewht priious due to its low soluility in methnol nd, hene, omprtively long ontt to the si onditions (N/). owever, when working t low temperture ( 10?0 C) in high dilution nd short-retion times (3 5 min), the prent sugr, 1,5-nhydro--rhmnulose 3 ould e relesed without ppreile formtion (TLC) of side produts; it ws hrterized s n morphous solid, whih in queous solution dopted the 2,2-dihydroxylted (monohydrte) form 3 2. The well-rystllizing dienzote of 1,5-nhydro-L-rhmnulose 15 ould e proured in either one of two wys: through hydroxylminolysis of the L-rhmnl ester 12 nd susequent trnsoximtion of the oxime 14?15, or, lterntively, y triutyltin hydride-promoted deromintion of the rhmnosulosyl romide 13. Not unexpetedly, -elimintion of enzoi id in 15 ws redily indued either y rief heting in pyridine or y stirring with sodium ette in etone to provide the single-stereogeni-entre dihydropyrnone 16, verstile enntiopure six-ron uilding lok (Sheme 2). Exposure of dihydropyrnone 16 to Zemplén methnolysis did not lierte the respetive 2,3-diketone (or enol forms thereof), ut gve the 2-dimethyl etl 17 in uniform retion, oneivly proeeding through ddition of methoxide onto the ronyl group nd susequent 4--?5--enzoyl migrtion (to the methyl yll 18) nd replement of the enzoyloxy group y (18?17). Suh ourse reeives some redene y the detetion of 19 y 1 NMR nd TLC on rief methnolysis, nd y the otention of enzoyl-llomltol 22 on the ttempt to nomerilly refuntionlize dihydropyrnone 16 y photoromintion with NBS (Sheme 3). As oserved for the 6- enzoyloxymethyl nlogue of 16, 9 the romine rdil either enters the nomeri position next to the ronyl group (?20) or the one vinologous thereto (?21), eh eing ple of elorting the -pyrone system vi enzoyl group shifts 10 (rrows in 20 nd 21, respetively). L-Rhmnose 4steps[8] 46% Bz Bz 12 R Br Bz Bz 13 d Bz Bz e X 14 X=N 15 X= f (15) Bz 16 g 17 Sheme 2. Retions nd onditions: () N/, 10?0 C, 84%; () NBS/ in C 2 Cl 2, 30 min, rt, 75%; 8 () N 2 /pyridine in Et, 5 d, rt, 86%; (d) Bu 3 Sn/AIBN in toluene, 5 h, 90 C, 71%; (e) etldehyde/cl in CN, 15 h, rt, 82%; (f) pyridine in CCl 3, 5 min reflux, 87%; (g) N/, 5 min, rt, 68%.

3 954 P. Jrglis et l. / Tetrhedron: Asymmetry 20 (2009) Ph Bz N R R=Bz 17 R= NBS hν Ph Ph Br or Br Bz Sheme ,5-Anhydro--xylulose Applition of the methodology developed for hydroxylminolysis nd Zemplén deyltion to the 2-hydroxy--xyll esters 23 nd 24 proeeded in strightforwrd mnner providing the E-oximes 25 27, the ulose dienzote 28, s well s the respetive diethyldithio etls 29 nd 30, in rystlline form eh nd in stisftory yields. The only peulirity oserved ws tht the form in whih the ulose dienzote 28 umulted on deoximtion of 26 with etldehyde depended on the workup proedure: the ketose s suh or its 2,2-diol (hydrte form), ws seprtely isolle, nd hrterized y their distintly different 1 nd 13 C NMR dt, the former showing its C-2 resonne t 199.4, the hydrte t 91.7 ppm (Sheme 4). Liertion of the unproteted 1,5-nhydro--xylulose 4 ould e effeted from the oxime 27 y trnsoximtion, from the dithioetl 30 y desulfuriztion nd, preprtively most strightforwrd, y Zemplén methnolysis of the 2-etoxy--xyll diette 23. The resulting 1,5-nhydro--pentulose ws hrterized y NMR to e the monohydrte in queous solution, whilst in MS-d 6 or in pyridine-d 5, spetr turned out to e unusully omplex inditing the presene of dimeri forms. R R R 23 R=A 24 R=Bz d (24) 4 e (27) h R R N 25 R=A 26 R=Bz 27 R= R EtS R EtS 29 R=Bz i 30 R= (26) f Bz Bz Bz Sheme 4. Retions nd onditions: () N 2 Cl in TF/ette uffer p 4.5, 20 h, rt or in pyridine 10 d, rt, 79% 25, 75% 26; () etldehyde/2 M Cl in CN, 18 h, rt, 92%; () N/, 1 h, rt, 63%; (d) N/, 2 h, 15 C?rt, then +, 69%; (e) etldehyde/2 M Cl in CN, 5 h, rt, 78%; (f) EtS/BF 3 in CCl 3, 5 min, rt, 88%; (g) pyridine in CCl 3, reflux, 10 min, 82%; (h) CdC 3 /gcl 2 in wter, 30 min, rt, 75%; (i) N/, 3 h, rt, 95%. g With respet to the onformtions dopted y 1,5-nhydro-xylulose 4 nd its derivtives 25 30, 1 NMR dt most notly their J 3,4 nd J 4,5 vlues revel the uloses 4 nd 28, respetively, nd their monohydrtes to e in the 4 C 1 onformtion, whilst the ouplings of the oximes sed on J 3,4 nd J 4,5 vlues of z re est interpreted y their doption of the 0 S 2 ottwist or skew onformtion. 3. Conlusion Bz Bz 4 R R 3 28 N R R 5 2 (R =) 28 2 (R =Bz) 25 R=A 26 R=Bz 27 R= Simple protools sed on diret Zemplén methnolysis or on three-step hydroxylminolysis/deyltion/deoximtion sequene hve een elorted to onvert 2-hydroxyglyl esters of -gltose, L-rhmnose nd -xylose into their onfigurtionlly relted 1,5-nhydro-ketoses. The onvenient ess therey provided to -tgtose, L-rhmnulose nd -xylulose in their 1,5- nhydro forms now renders them ville for evlution of their pplition profiles, most notly of their potentil ntioxidnt properties. Moreover, the methodologies developed for their quisition re pt to e pplile to ny other 2-hydroxyglyl ester, suh s, for exmple, to the perettes of 2-hydroxy- -gull 32, 11 2-hydroxy--lll 33 11,12 nd 2-hydroxy-elloil 34, 13 insmuh s their enol ester hydroxylminolysis smoothly provides the respetive E-oximes in rystlline form eh. Thus, the low temperture Zemplén de--etyltions elorted should similrly proeed in strightforwrd mnner furnishing, for exmple, 1,5-nhydro--sorose from 32 nd its -psio nlogue from 33. In similr fshion, the redily essile dishride-derived 2-hydroxyglyl esters nd their enzoylted mltl, elloil nd ltl nlogues 14 re to generte the underlying 4- -glyosylted 1,5-nhydro--frutoses, should there e need for their vilility.

4 P. Jrglis et l. / Tetrhedron: Asymmetry 20 (2009) A A A A A A (-soro) A N A A A A A A (-psio) A N A A A A A 34 A A A A A N A 37 A A 4. n the E-geometry of 1,5-nhydroketose oximes ximes of pyrnoid 2-ketosugrs, tht is, --glyosiduloses of type I, invrily ssume the Z geometry with the oxime hydroxyl pointing in the diretion of the nomeri entre, proof eing derived from the signifint deshielding of the equtorilly oriented -1 y the oxime hydroxyl whih finds expression in n downfield shift of ppm when going from the prent ketose to its oxime. 15 The Z ssignments were in ft orroorted y severl X-ry strutures. 16 A A I A 1e N X X=Alkyl,A,Cl R R X II 1e N X=,C 3,C 2 R R=,A,Bz Compounds differing from I only y the sene of n nomeri sustituent, tht is, 1,5-nhydroketoximes of type II, would similrly e ntiipted to generlly dopt the E-oxime geometry. This onjeture ould redily e verified y omprison of 1 nd 13 C NMR dt of the oximes nd their prent 2-oxo nlogues. As lerly evident from the juxtposition of the -fruto-onfigured oximes 37 nd to their 2-ulose ounterprts 38 nd 39, the xilly-oriented protons -1 nd -3 show minimlly hnged hemil shifts (f. Tle 1), wheres the equtoril -1 exhiits distint downwrd shift of 0.6 ppm when going from ulose to oxime. This lerly indites tht the oxime hydroxyl group is pointing towrds the nomeri ron rther thn C-3, hene estlishing the E-onfigurtion for oximes R R R' R 3 R 1 1e 1 R = 38 R = A 39 R = Bz 3 R R R A A 1e 42 Bz Bz 37 A βa 4Gl N 43 Bz βbz 4Gl 1 44 Bz αbz 4Gl 45 Bz βbz4gl In the -tgto nd L-rhmnulo ses the respetive downfield shifts for -1e from ketose to oxime re even higher (0.8 ppm), whih n only e rtionlized y the E-geometry of the oximes. In the -xylulo se 28 (Tle 1, X = ) nd 26 (X = N) there is downfield shift of oth, -1e (0.23) nd -1 (0.27 ppm) oviously due dption of the 0 S 2 ot-twist onformtion of the pyrnoid ring, wherein the oxime hydroxyl exerts its deshielding eqully on either of the nomeri hydrogens. The E-geometry of 1,5-nhydroketoximes n similrly e derived from the 13 C hemil shifts of the rons viinl to the ronyl respetively, oximinoronyl group. As doumented y vst literture dt, 17,18 the 13 C resonnes of the ronyl nd oth viinl rons shift upfield on oxime formtion, with the effet for the ron on the sme side s the N group eing greter thn tht for the other. In the se of 3-methyl ylohexnone nd its oxime these upfield shifts re 15.8 ppm for the oxime- deshielded ron, yet still 9.6 ppm for the other (Fig. 1). N Figure C hemil shifts (ppm) of ylohexnone versus those of its oxime. 17 The upfield shift for C-2 from ketone to oxime is signifintly lrger (15.8) thn for C-6 (9.6 ppm). Tle 1 1 NMR dt for -1 nd the nomeri hydrogens of 1,5-nhydroketoses nd ylted derivtives in omprison to those of their E-oximes Configurtion 1,5-Anhydroketoses 1,5-Anhydroketose E-oximes Ref. X = X = N -1e -1-3 Solvent -1e -1-3 Solvent -Fruto CCl MS-d MS-d CCl MS-d CCl CCl CCl Tgto MS-d MS-d MS-d 6 L-Rhmnulo CCl CCl 3 -Xylulo MS-d CCl C-d CCl 3 1,5-Anhydro--frutose 1 nd its -xylulo nlogue 4 dopt in wter ( 2 ) the 2,2-dihydroxy(hydrte) form, nd hene re not suited for omprison. t from this pper. Signl not resolved from glyosyl protons.

5 956 P. Jrglis et l. / Tetrhedron: Asymmetry 20 (2009) Tle 2 13 C NMR dt (ppm) for C-1 through C-3 of 1,5-nhydro-ketoses nd ylted derivtives ompred to those of their E-oximes Configurtion 1,5-Anhydroketoses 1,5-Anhydroketoximes Compd. C-1 C-2 C-3 Solvent Compd. C-1 C-2 C-3 Solvent -Fruto Fruto CCl MS-d 6 -Fruto MS-d CCl 3 -Tgto MS-d 6 -xylulo C-d CCl 3 1,5-Anhydro--frutose 1 forms dimers in the solid stte nd the hydrte in wter, hene is unsuited for omprison. Anlogous shift differenes re oserved for the 13 C resonnes of the four ketose/oxime exmples listed in Tle 2: in the -fruto nd -tgto onfigured ompounds upfield shifts of ppm for the viinl ron deshielded y the oxime hydroxyl, nd 6 7 ppm only for the other, thus eqully proving the E-geometry of the 1,5-nhydroketoximes. In the -xylulose se though this upfield shift differene etween ketose nd ketoxime is nerly equlized understndly, s the 0 S 2 skew-ot onformtion of the pyrnoid ring levels the deshielding effets. 5. Experimentl 5.1. Generl lting points were determined with Bok hot-stge mirosope nd re unorreted. ptil rottions were mesured on Perkin Elmer 241 polrimeter t 20 C using ell of 1 dm pth length; onentrtion () in g/100 ml nd solvent re given in prentheses. 1 nd 13 C NMR spetr were reorded on Bruker ARX-300 spetrometer in CCl 3. Mss spetr were quired on Vrin MAT 311 spetrometer. Mironlyses were determined on Perkin Elmer 240 elementl nlyzer. Anlytil thin lyer hromtogrphy (TLC) ws performed on preoted rk plsti sheets (0.2 mm Sili Gel 60 F 254 ) with detetion y UV light (254 nm) nd either sprying with 2 S 4 (50%) or y dipping into sulphuri id/nisldehyde regent [ontining nisldehyde (1 ml), ond 2 S 4 (9 ml) A (10 ml) nd (85 ml)] followed y heting t 110 C for 10 min. Column nd flsh hromtogrphy ws rried out on Fluk Sili Gel 60 ( mesh) using the speified eluents ,4,6-Tri--etyl-1,5-nhydro--tgtose E-oxime 6 To solution of hydroxylmine hydrohloride (7.4 g) in pyridine (50 ml) ws dded 10.0 g (30.3 mmol) of 2-etoxy--gltl triette 5 19,20 nd the mixture ws stirred t mient temperture for 15 h, followed y pouring into wter (350 ml). Extrtion with CCl 3 (5 100 ml) nd onseutive wshing of the omined extrts with 2 N 2 S 4 (3 100 ml), wter (100 ml), std NC 3 solution (100 ml) nd wter (50 ml), drying (N 2 S 4 ) nd evportion to dryness in vuo left solid residue whih ws rerystllized from Et: 7.51 g (82%) of 6 s well-formed prisms of mp C; ½Š 23 ¼ 44:3 ( 0.5, CCl 3). 1 NMR (300 Mz, MS-d 6 ): d 2.01, 2.03, 2.08 (three 3-s, 3 AC 3 ), 3.94 (1-d, 1-), 3.98 (2-m, 6-2 ), 4.18 (1-dd, 5-), 5.01 (1-d, 1-e), 5.39 (1-d, 4- ), 5.76 (1-d, 3-), (1-s, N), J 1,1 = 14.5, J 3,4 = 3.7, J 4,5 = 0 z. 13 C NMR (75.5 Mz, MS-d 6 ): d 20.2, 20.38, (3 AC 3 ), 60.3 (C-1), 62.1 (C-6), 68.2 nd 68.9 (C-3, C-4), 73.5 (C-5), (C-2), 168.9, 169.9, (3 AC). Anl. Cld for C N 8 (303.26): C, 47.52;, 5.65; N, Found: C, 47.58;, 5.57; N, ,5-Anhydro--tgtose E-oxime 7 Fifty millilitres of 1 M N/ solution were ooled to 0 C with stirring nd oxime 6 (3.03 g, 10 mmol) ws dded, TLC showing omplete onversion within 20 min with the exlusive formtion of 7 (R f = 0.5 in npr/wter 7:3). The solution ws diluted with 200 ml of nd neutrlised y stirring with owex 50 WX8, + form for 10 min. The suspension ws filtered nd the resin ws wshed with methnol. Filtrte nd wshings were evported to volume of out 50 ml whereupon rystlliztion ourred. The preipitte ws redissolved y wrming to llow smooth rystlliztion: 3.05 g (78%) of 7 s fine needles of mp C; ½Š 20 ¼ 12:8 ( 1, ), ½Š22 ¼ 5:0 ( 1, 2); lit. 6 : mp C; ½Š ¼ 9:2 ( 0.5, ). 1 NMR (300 Mz, MS-d 6 ) fter two reevportions from 2 to eliminte, ouplings: d 3.47 (3-m, 5-, 6-2 ), 3.68 (1-d, 1- ), 3.82 (dd, 1, 4-), 4.23 (dd, 1, 3-), 4.85 (1, -1e), (1-s, N), J 1,1 = 13.9, J 3,4 = 3.3, J 4,5 = 0.5 z. 13 C NMR (25.2 Mz, MS-d 6 ): d 59.4 (C-1), 60.4 (C-6), 69.5 nd 69.9 (C-3 nd C-4), 78.3 (C-5), (C-2). MS (F): m/e = 177 (M + ). Anl. Cld for C 6 11 N 5 (177.16): C, 40.68;, 6.26; N, Found: C, 40.43;, 6.19; N, ,4,6-Tri--etyl-1,5-nhydro--tgtose 8 Stirring of 7 in etonitrile solution (4.60 g, 15.2 mmol, in 50 ml) with etldehyde (3.0 ml) nd 1 M Cl (15 ml) for 6 h t mient temperture followed y dilution with wter (250 ml), extrtion with EtA (3 100 ml) nd removl of the solvent from the orgni lyer gve glssy syrup (4.5 g, 95%), whih on the sis of 1 NMR dt in MS-d 6 omprised 2:3 mixture of the keto form 8 nd its monohydrte whih due to its propensity for elimintion of eti id to the enolone 11 in ontt with sili gel ws not ttempted to seprte. 1 NMR (300 Mz, MS-d 6 ), keto form: d 2.03, 2.06 (3 nd 6-s, 3 AC 3 ), 4.05 nd 4.08 (two 1-m, A nd B prt of n ABX system, 6-2 ), 4.09 nd 4.38 (two 1-d, 1-2 ), 4.54 (1-m, X prt of n ABX system, 5-), 5.67 (dd, 1, 4-), 5.88 (1-d, 3-), J 1,1 = 14.5, J 3,4 = 4.0, J 4,5 = 0.9 z; monohydrte: 4.99 (1-d, 3-), 5.23 (dd, 1, 4-), 7.39 nd 7.60 (two 1-s, 2, exhngele with 2, J 3,4 = 5.3, J 4,5 = 5.8 z ,5-Anhydro--tgtose eoximtion of oxime 7 Aetldehyde (1.7 ml, 30 mmol) nd 1 M Cl (15 ml) were dded to suspension of 7 (1.43 g, 8 mmol) in etonitrile (50 ml) nd the mixture ws stirred for 5 h t mient temperture. The resulting ler solution ws diluted with wter (15 ml) nd neutrlised y stirring with n idi resin (Amerlite IR form) nd the filtrte ws evported to dryness in vuo. The syrupy residue ws then eluted from sili gel olumn (3 45 m) with n-propnol/wter (7:3), to give upon evportion of the produt-rrying elutes in vuo, finlly t 0.01 mm, 1.08 g (83%) of 2 s n morphous solid of R f = 0.5 in 7:3 n-pr/wter (extended spot); ½Š 21 ¼ 7:9 ( 0.9, 2); lit. 6 : ½Š ¼ 6:8 ( 1.1, ); MS (F): m/e = 162 [M + ], 163 (M+1), 180 (M+ 2 ). Anl.

6 P. Jrglis et l. / Tetrhedron: Asymmetry 20 (2009) Cld for C (162.14): C, 44.44;, Found: C, 44.29, NMR dt in 2 indite n pproximte 3:2 equilirium etween ketose nd monohydrte form, s previously oserved y Freimund nd Köpper 7 for produt prepred y enzymti oxidtion of 1,5-nhydro--gltitol. 1 NMR (500 Mz, 2 ), keto form: 3.58 (2-m, 6-2 ), 3.92 (2-m, -1, -5), 4.04 (1-d, - 1e) 4.20 (1-dd, -4), 4.45 (1-d, -3); J 1,1 = 14.8; J 3,4 = 3.9, J 4,5 = 0.9 z; hydrte: 3.23 (1-d, -1), 3.43 (1-m, -5), 3.50 nd 3.55 (AB prt of n ABX system, 6-2 ), 3.54 (1-d, -3), 3.59 (1-d, -1e), 3.76 (1-dd, -4); J 1,1 = 12.0, J 3,4 = 3.8; J 4,5 = C NMR (75.2 Mz, 2 ). d (C-2, ketose), 92.5 (C-2, hydrte), 79.9/78.6 (C-5), 76.1/72.1 (C-3), 72.5/72.6 (C-1), 71.7/69.5 (C-4), 61.5/61.3 (C-6) e--etyltion of 2-etoxy--gltl triette 5 A solution of 5 19,20 (2.0 g, 6 mmol) in dry (100 ml) ws ooled to out 15 C (slt ie mixture) followed y the ddition of 5 ml of 1 M N/ solution nd stirring of the mixture for 2 h t 15 C, wherefter the solution ws llowed to wrm to 0 C (1 h). Neutrliztion ws then effeted y stirring with Amerlite IR 120, + form (10 min). Filtrtion nd evportion to dryness in vuo gve slightly yellowish, syrupy residue (910 mg) whih ws eluted from Sephdex L 20 olumn (2 30 m) with wter. Colleting the produt-rrying elutes nd removl of the solvent in vuo, finlly t 0.05 Torr, gve 820 mg (84%) of 2 s n morphous solid, identil with the produt desried under emerptliztion of dithioetl 10 To solution of 1.0 g (2.7 mmol) of 10 in 20 ml of wter were dded CdC 3 (1.8 g, 10 mmol) nd gcl 2 (1.4 g, 5 mmol), nd the mixture ws stirred for 30 min t mient temperture. The insolule mterils re susequently removed y filtrtion through lyer of sili gel. The filtrte ws then sturted with 2 S, nd fter nother filtrtion with sution through sili gel the filtrte ws neutrlised with wekly si ion exhnge resin (Lewtit MP 7080). Removl of the resin nd onentrtion to dryness in vuo left visous syrup whih ws purified y elution from Sephdex L 20 olumn (2 30 m) with wter. Removl of the solvent in vuo from the produt-rrying elutes nd drying of the residue t 0.1 Torr gve 425 mg (69%) of olourless fom, identil (TLC, NMR) with the produt desried under ,4,6-Tri--etyl-1,5-nhydro--tgtose diethyldithioetl 9 Ethnediol (3.7 ml, 50 mmol) nd BF 3 -etherte solution (10 ml) were dded to solution of 1.9 g (10 mmol) of nhydrotgtose triette 8 (mixture of ulose nd hydrte s otined under 5.4) in CCl 3 (30 ml). After 15 min of stirring t mient temperture, the solution ws diluted with 50 ml of CCl 3, neutrlised y wshing with 2 M N nd wter (3 30 ml), dried (N 2 S 4 ) nd evported to dryness in vuo. The resulting syrup, 2.23 g (61%) of 9, ws hromtogrphilly uniform (R f = 0.59 in toluene/etone 2:1) nd ws used for the deetyltion (f. elow). The nlytil smple ws purified y elution from sili gel with 40:1 C 2 Cl 2 /EtA: syrup of ½Š 23 ¼þ15:7 ( 1, CCl 3). 1 NMR (300 Mz, MS-d 6 ): d 1.14 nd 1.16 (two 3-t, 2 EtS- C 3 ), 2.00 nd 2.05 (6- nd 3-s, 3 AC 3 ), 2.65 (4-m, 2 EtSC 2 ), 3.74 nd 3.99 (two 1-d, 1-2 ), 3.99 (1-m, 5-), 4.17 (2-m, 6-2 ), 5.25 (1-dd, 4-), 5.31 (1-d, 3-), J 1,1 = 12.5, J 3,4 = 3.7, J 4,5 = 3.2 z. 13 C NMR (25.2 Mz, CCl 3 ): d 60.3 (C-2), 61.2 (C-6), 66.6 (C-4), 70.3 (C-1), 73.9 nd 74.6 (C-3 nd C-5). Anl. Cld for C S 2 (394.5): C, 48.71;, Found: C, 48.70;, ,5-Anhydro--tgtose diethyldithioetl 10 A solution of 1.54 g (4.1 mmol) of triette 9 in 40 ml of 0.1 M methnoli sodium methoxide ws stirred t 0 C for 3 h nd susequently neutrlised y stirring with owex WXl ( + form). Filtrtion nd evportion of the filtrte in vuo fforded syrup, whih ws hromtogrphed on sili gel (2 30 m olumn) y elution with 2:1 toluene/eta to result in 910 mg (87%) of 10 s olourless syrup of ½Š 20 ¼ 57 ( 1.1, ); R f = 0.43 in n-utnone std with wter. 13 C NMR (25.2 Mz, 2 ): d 61.9 (C-6), 62.4 (C-2), 67.4 (C-4), 72.9 (C-1), 74.6 nd 81.5 (C-3 nd C-5). MS (F): m/e = 268 (M + ), 269 (M + + 1). Anl. Cld for C S 2 (268.4): C, 44.75;, Found: C, 44.70;, (6S)-4-Aetoxy-6-etoxymethyl-2-pyrn-3(6)-one 11 A 1.0 g portion of 8 nd freshly molten NA (2.0 g) were stirred in 50 ml of dry etone for 1 h t room temperture. Filtrtion nd evportion of the filtrte in vuo, nd purifition of the resulting syrup on sili gel olumn (2 30 m) y fst elution with 3:1 n-hexne/eta fforded 1.03 g (91%) of enolone 11 s olourless syrup; ½Š 20 ¼ 42:7 ( 1.2, CCl 3); lit. 7,21 : ¼ 17:7 ( 0.34, C 2Cl 2 ); 1 ½Š ¼ 43:7 ( 1.7, CCl 3 ) nd 13 C NMR dt orresponded with those reported. 7,21 ½Š ,5-Anhydro-L-rhmnulose (1,5-nhydro-6-deoxy-Lfrutose) 3 Five mmol (2.29 g) of 12 8 ws dissolved in 150 ml of nhydrous with slight wrming, then ooled to 5 C with vigorous stirring followed y the ddition of 5 ml of 1 M N/ solution. The mixture ws llowed to wrm to 0?+5 C ny preipitte ourring eing dissolved within 10 min. After out 20 min (TLC monitoring with n-pr/wter 9:1 or 7:3, R f of produt 0.65 nd 0.72, respetively), the retion ws quenhed y stirring with methnol-wshed Amerlite IR 120 ( + form). Filtrtion nd evportion of the filtrte to dryness in vuo left syrup whih ws dissolved in wter nd eluted from Sephdex L 20 olumn (2 30 m) with wter. Evportion of the produt-rrying elutes in vuo, finlly t 0.1 Torr, gve 405 mg (69%) of 3 s n morphous solid. 1 NMR (500 Mz, 2 ): d 1.20 (3-d, C 3 ), 3.16 (1-t, -4), 3.34 (1ddd, -5), 3.37 (1-d, -1), 3.44 (1-d, -3), 3.63 (1-d, - 1e); J 1,1 = 12.3, J 3,4 = J 4,5 = 9.3, J 5,6 = 6.2 z. 13 C NMR (125.7 Mz, 2 ): d 17.4 (C-6), 72.3 (C-1), 74.6 (C-4), 77.0 nd 77.1 (C-3 nd C-5), 93.2 (C-2): Anl. Cld for C (146.14): C, 49.31;, Found: C, 49.24;, ,4-i--enzoyl-1,5-nhydro-L-rhmnulose E-oxime 14 2-Benzoyloxy-L-rhmnl dienzote 12 8 (9.20 g, 20 mmol) ws dded to solution of N 3 Cl (3.5 g, 50 mmol) in 1:1 pyridine/et (100 ml) nd the mixture ws kept t mient temperture for one week nd susequently tken to dryness in vuo. The residue ws dissolved in C 2 Cl 2 (100 ml) nd suessively wshed with 2 M Cl (20 ml) nd std NC 3 solution (2 20 ml), dried (N 2 S 4 ), followed y removl of the solvent in vuo nd rystlliztion of the residue y triturtion with Et: 6.35 g (86%) of 14 s olourless needles; mp C, ½Š 21 ¼þ123 ( 0.5, CCl 3). 1 NMR (300 Mz, CCl 3 ): d 1.35 (3-d, C 3 ), 3.75 (1-m, 5-), 4.00 nd 5.12 (two 1-d, 1-2 ), 5.36 (1-t, 4-), 5.94 (1-d, 3-), (10-m, 2 C 6 5 ), 8.44 (1-s, N); J 1,1 = 16.0, J 3,4 = J 4,5 = 8.0, J 5,6 = 5.9 z. Anl. Cld for C N 6 (369.36): C, 65.03;, 5.19; N, Found: C, 64.91;, 5.10; N, 3.71.

7 958 P. Jrglis et l. / Tetrhedron: Asymmetry 20 (2009) ,4-i--enzoyl-1,5-nhydro-L-rhmnulose eoximtion of oxime 14 Stirring of 14 (3.69 g, 10 mmol) in etonitrile solution (50 ml) with etldehyde (2.3 ml, 40 mmol) nd 2 M Cl (5 ml, 10 mmol) ws done overnight t mient temperture followed y dilution with wter (200 ml) nd extrtion with EtA (3 100 ml). Removl of the solvent from the extrts gve syrup whih rystllized from ether: 2.80 g (79%) of 15 s olourless needles of mp C, ½Š 21 ¼þ109:9 ( 1.1, CCl 3 ). 1 NMR (300 Mz, CCl 3 ): d 1.41 (3-d, C 3 ), 4.11 (1-m, 5-), 4.16 nd 4.33 (two 1-d, 1-2 ), 5.56 (1-t, 4-), 5.86 (1-d, 3-), 7.4 nd 8.0 (two m, 2 C 6 5 ); J 1,1 = 15.8, J 3,4 = J 4,5 = 7.9 z. Anl. Cld for C (354.34): C, 67.79;, Found: C, 67.69;, Redutive deromintion of ulosyl romide 13 To solution of 13 8 (1.1 g, 2 mmol) in toluene (50 ml) were dded zoisoutyronitrile (50 mg, 0.3 mmol) nd triutyltin hydride (880 mg, 3 mmol) nd the mixture ws heted for 5 h t 90 C, followed y ooling nd wshing with 10% queous KF solution (3 20 ml) nd wter. rying (MgS 4 ) nd removl of the solvent in vuo left n oily residue, uniform y TLC, whih ws freed from tin ompounds y rpid hromtogrphy on sili gel olumn (2 20 m) with 2:1 ether/n-pentne pplying pressure to effet this opertion within 10 min. The syrup remining fter evportion of the elute ontining 15 rystllized on triturtion with C 2 Cl 2 /n-hexne to fford 505 mg (71%), identil with the produt desried under Longer ontt of rude 15 with sili gel, for exmple, severl hours on olumn purifition, indued -elimintion of enzoi id to the dihydropyrn one 17; it my e isolted in yields over 80% y slow elution of sili gel olumn (3 30 m) with 2:1 ether/n-pentne (6S)-4-Benzoyloxy-6-methyl-2-pyrn-3(6)-one 16 Pyridine (0.3 ml) ws dded to solution of 15 (1.42 g, 4 mmol) in CCl 3 (10 ml) nd the mixture ws heted for 5 min, followed y evportion to dryness in vuo. Crystlliztion of the residue from fforded 810 g (87%) of 16 s olourless needles; mp 116 C; ½Š 21 ¼ 10:5 ( 1.2, CCl 3). 1 NMR (300 Mz, CCl 3 ): d 1.49 (3-d, C 3 ), 4.26 nd 4.42 (two 1-d, 2-2 ), 4.76 (1-ddt, 6-), 6.72 (1-d, 5-), (5-m, C 6 5 ); J 2,6 = J 5,6 = 1.9, J 6;C3 ¼ 6:9 z. Anl. Cld for C (232.23): C, 67.23;, Found: C, 67.26;, (2S)-5,5-imethoxy-2-methyl-tetrhydropyrn-4-one 17 Two millilitres of 1 M N/ solution were stirred into suspension of enolone 16 (465 mg, 2 mmol) in dry (10 ml) nd the mixture ws neutrlised fter 5 min y ddition of Amerlite IR ( + form). Filtrtion nd evportion of the filtrte to dryness gve olourless oil, whih n e purified y hromtogrphy ( m sili gel olumn, elution with CCl 4 /EtA 2:1) or distilltion t 65 C/0.3 Torr: 235 mg (68%) of 17; ¼ þ154:6 ( 1.3, CCl 3); 1 NMR (300 Mz, CCl 3 ): d 1.33 (3-d, C 3 ), 2.43 nd 2.71 (two 1-d, 3-2 ), 3.29 nd 3.39 (two 3-s, 2 C 3 ), 3.76 (1-ddq, 2-), 3.38 nd 4.24 (two 1-d, 6-2 ); J 2,3 = 2.5 nd 11.0, J 2;C3 ¼ 6:1, J 3,3 = 13.3, J 6,6 = 12.4 z. 13 C NMR (75.5 Mz, CCl 3 ): d 21.5 (C 3 ), 41.4 (C-3), 49.9 (C 3 ), 71.0 (C-6), 75.6 (C-2), 98.3 (C-5), C-4. MS (F, 5 ma): m/ e = 174 (M + ). Anl. Cld for C (174.18): C, 55.17;, Found: C, 54.98;, ½Š Benzoyloxy-2-methyl-4-pyrn-4-one (-enzoylllomltol) 22 N-Bromosuinimide (360 mg, 2.5 mmol) nd BC 3 (0.5 g) were dded to solution of enolone 16 (465 mg, 2 mmol) in Et-free CCl 4 (40 ml), nd the mixture ws irrdited with 450 W IR lmp with vigorous stirring for 20 min, wherefter TLC in 19:1 C 2 Cl 2 /EtA reveled the sene of edut in fvour of severl produts. The mjor one, 22, ws isolted y filtrtion, evportion of the filtrte to dryness nd solution of the residue from sili gel olumn (2 20 m) with 19:1 C 2 Cl 2 /EtA nd rystlliztion from diisopropyl ether: 205 mg (44%) of 22 s needles of mp C. The produt ws identil (mixed mp, 1 NMR) with n uthenti smple ,4-i--etyl-1,5-nhydro--threo-pent-2-ulose E- oxime 25 A mixture of 2,3,4-tri--etyl-1,5-nhydro- -threo-pent-1- enitol (1.03 g, 4 mmol), hydroxylmine hydrohloride (1.0 g), tetrhydrofurn (10 ml) nd ette uffer (p 4.5) ws stirred for 20 h t mient temperture, followed y grdul neutrliztion with std NC 3 solution nd extrtions with CCl 3 (3 20 ml). The CCl 3 extrts were wshed with wter, dried (N 2 S 4 ) nd tken to dryness in vuo. The syrupy residue rystllized on triturtion with Et: 730 mg (79%) of 25 s needles of mp C; ½Š 22 ¼ 58:3(0.3, CCl 3). 1 NMR (300 Mz, CCl 3 ): d 2.06 nd 2.08 (two 3-s, 2 A C 3 ), 3.92 (1-dd, 5-x), 4.28 nd 4.52 (two 14.1 z-d, 1 eh, 1-2 ), 4.66 (1-dd, 5-eq), 4.90 (1-sx, 4-), 5.36 (1-d, 3-), (1-s, N), J 1,1 = 14.1, J 3,4 = 5.0, J 4,5 = 3.1 nd 5.0, J 5,5 = 12.2 z. Anl. Cld for C 9 13 N 6 (231.20): C, 46.75;, 5.67; N, Found: C, 46.70;, 5.59; N, ,4-i--enzoyl-1,5-nhydro--threo-pent-2-ulose E- oxime 26 ydroxylmine hydrohloride (10.0 g, 1.4 mmol) ws dded to solution of 2,3,4-tri--enzoyl-1,5-nhydro--threo-pent-1-enitol (10.0 g, 22.5 mmol) in pyridine (60 ml) nd the mixture ws stirred for 1 h nd then stood for 5 d t mient temperture, followed y stirring into wter (1.5 ml). The preipitte formed ws filtered off, wshed with wter, dried (N 2 S 4 ) nd rerystllized from CCl 3 /Et to give 9.4 g (75%) of olourless needles of mp C, whih onsisted of 10:1 mixture ( 1 NMR) of the E-oxime 26 (R f = 0.56 in 10:1 C 2 Cl 2 /EtA) nd the respetive Z-isomer (R f = 0.49). A 500 mg smple ws sujeted to elution from sili gel olumn (2 20 m) with C 2 Cl 2 /EtA 30:1, the first frtions ontining 220 mg of the pure E-isomer; mp C; ½Š 23 ¼ 111 ( 0.6, CCl 3 ). 1 NMR (500 Mz, CCl 3 ): d 3.89 nd 4.13 (two 1-dd, 5-2 ), 4.48 nd 4.67 (two 1-d, 1-2 ), 5.37 (1-ddd, 4-), 5.86 (1-d, 3-), J 1,1 = 15.1, J 3,4 = 5.6, J 4,5 = 3.4 nd 4.5, J 5,5 = 12.7 z. 13 C NMR (125.7 Mz, CCl 3 ): d 61.7 (C-1), 67.4 (C-5), 69.8 (C-3), 71.0 (C-4), 151,4 ((C-2). Anl. Cld for C N 6 (355.33): C, 64.22;, 4.82; N, Found: C, 64.08;, 4.75; N, The further frtions onsisted of E/Z-mixtures in vrious rtios, whih were not further seprted. 1 NMR (500 Mz, CCl 3 for Z- form): d 4.10 (2-m, 5-2 ), 4.28 nd 4.37 (two 13.0 z-d, 1 eh, 1-2 ), 5.27 (1-ddd, 4-), 6.50 (d, 1, 3-), J 1,1 = 13.0, J 3,4 = J 4,5 = z; most distint differene etween the E/Z-isomers is the hemil shift for -3: 5.86 (E) vs ppm for the Z-form ,5-Anhydro--threo-pent-2-ulose E-oxime 27 xime 26 (3.55 g, 10 mmol, in the form of its 10:1 E/Z-mixture otined ove) ws dissolved in 50 ml ooled (0 C) 1 M N/

8 P. Jrglis et l. / Tetrhedron: Asymmetry 20 (2009) solution nd stirred for 1 h. Susequent neutrliztion with owex 50 WX8 ( + form) filtrtion nd evportion to dryness in vuo left syrup whih ws dissolved in wter (30 ml) nd wshed with ether to remove methyl enzote. The syrup remining fter evportion of the queous phse to dryness in vuo rystllized from wter/i-propnol. Rerystlliztion from the sme solvents fforded 0.93 g (63%) of 27 s fine prisms of mp C; ½Š 20 ¼þ14:8 ( 1, 2). 1 NMR (300 Mz, MSd 6 ): d 3.45 nd 3.76 (two 1-dd, AB prt of ABX system, 5-2 ), 3.54 (1-m, X prt, 4-), 3.90 (1-dd, 3-), 4.04 nd 4.48 (two 1-d, 1-2 ), 5.01 nd 5.32 (two 1-d, 2 ), (1-s, N); J 1,1 = 13.8, J 3,4 = 4.2, J 4,5 = 2.2 nd 3.6, J 5,5 = 11.6 z. 13 C NMR (75.47 Mz, MS-d 6 ): d 58.8 (C-1), 67.3 (C-5), 69.8 (C-3), 70.1 (C-4), (C-2). Anl. Cld for C 5 9 N 4 (147.13): C, 40.81;, 6.17; N, Found: C, 40.72;, 6.12; N, ,4-i--enzoyl-1,5-nhydro--pentulose Monohydrte Pentulose oxime 26 (10.0 g, 30 mmol), in the form of its 10:1 E/Zmixture s otined ove, ws stirred with mixture of etonitrile (250 ml), 2 M Cl (18 ml) nd etldehyde (10 ml) t mient temperture for 18 h nd susequently poured into wter (1 L) with vigorous stirring. The resulting preipitte ws filtered, wshed with wter nd dried (CCl 2 ). issolution in the minimum mount of methnol nd triturtion with 2:1 ylohexne/ether resulted in rystlliztion: 9.3 g (92%) of 28-monohydrte; mp C, ¼ 131 ( 0.6, CCl 3). 1 NMR (300 Mz, MS-d 6 ): d 3.47 nd 3.66 (two 11.5 z-d, 1 eh, 1-2 ), 3.54 nd 4.06 (two 1-ddd, 5-2 ), 5.23 (1-ddd, 4-), 5.38 (d, 1, 3-), 6.20 nd 6.28 (two 1-s, 2, exhngele with 2 ), (10-m, 2 C 6 5 ); J 1,1 = 11.5, ½Š 20 J 3,4 = 9.3, J 4,5 = 5.0 nd 9.7, J 5,5 = 11.0 z. 13 C NMR (75.5 Mz, MS-d 6 ): d 66.7 (C-1), 70.1 (C-4), 78.5 (C-5), 75.9 (C-3), 91.7 (C- 2). Anl. Cld for C (358.33): C, 63.68;, Found: C, 63.54;, Keto-form The retion mixture resulting from deoximtion s desried ove (fter stirring for 18 h), ws sujeted to different workup, y elution with wter (500 ml), extrtion with EtA (3 200 ml), wshing of the omined extrts with wter, drying (N 2 S 4 ) nd removl of the solvent in vuo. The resulting syrup rystllized C 2 Cl 2 /n-hexne or CCl 4 : 8.1 g (75%) of 28 s n morphous produt of mp C nd ½Š 20 ¼ 117 ( 0.6, CCl 3), whih ppered (NMR) to ontin only smll mounts of the monohydrte. 1 NMR (300 Mz, etone- 6 ): d 4.16 (1-dd, 5- ), 4.21 nd 4.44 (two 1-d, 1-2 ), 4.46 (1-ddd, 5-e), 5.73 (1-ddd, 4-), 6.13 (1-d, 3-); J 1,1 = 15.0, J 1,5 = 1.1, J 3,4 = 9.0, J 4,5 = 8.0 nd 5.1, J 5,5 = 12 z. 13 C NMR (75.5 Mz, MS-d 6 ): d 67.5 (C-1), 71.6 (C-4), 73.4 (C-5), 77.3 (C-3), (C-2). Anl. Cld for C (340.32): C, 67.05;, Found: C, 66.85;, ,5-Anhydro--xylulose (1,5-nhydro--threo-pentulose) eoximtion of oxime 27 Aetldehyde (0.56 ml, 10 mmol) nd 1 M Cl (5 ml) were dded to suspension of oxime 27 (440 mg, 3 mmol) in etonitrile (15 ml) nd the mixture ws stirred for 5 h t mient temperture. The resulting ler solution ws diluted with wter (5 ml) nd neutrlised y stirring with n idi resin (Amerlite IR form) nd the filtrte ws evported to dryness in vuo. The syrupy residue ws then eluted from sili gel olumn (2 15 m) with 7:3 n-propnol/wter, to give upon evportion of the produt-rrying elutes in vuo, finlly t 0.01 mm, 265 mg (67%) of 4 s fluffy solid. 1 NMR (300 Mz, 2, 2 h fter solution): d 3.38 nd 3.69 (two 1-d, 1-2 ), 3.40 (1-t, 4-), 3.54 (1-d, 3-), 3.60 nd 3.94 (two 1-dd, 5-2 ), J 1,1 = 12.4, J 3,4 = 8.7, J 4,5 = 7.9 nd 4.7 z. 13 C NMR (75.5 Mz, 2 ): d 66.9 (C-1), 70.2 (C-4), 71.9 (C-3), 78.2 (C-5), 92.5 (C-2). Anl. Cld for C (132.11): C, 45.45;, Found: C, 45.34;, e--etyltion of 2-etoxy--xyll diette 23 A methnoli solution of (1.29 g, 5 mmol, in 80 ml) ws ooled to 15 C (ie slt mixture), nd upon dropwise ddition of 1 M N/ (5 ml) the mixture ws llowed to ome to 0 C within out 1 h (TLC monitoring with n-pr/wter 7:3). Susequent quenhing y stirring methnol-wshed Amerlite IR 120 ( + form) into the still old solution. Filtrtion, evportion of the filtrte in vuo, elution of the residue from n L 20 Sephdex olumn (2 25 m) with wter, evportion of the produt-rrying elutes nd drying, finlly t 0.1 Torr, gve 440 mg (67%) of 4 s fom, identil with respet to 1 nd 13 C NMR dt with the produt desried ove. esulfuriztion of dithioetl y stirring n queous solution with CdC 3 /gcl 2 s desried for 10?2 nd nlogous workup similrly gve 4 in 75% yield ,4-i--enzoyl-1,5-nhydro--threo-pentulose diethyldithioetl 29 Ethnthiol (7.0 ml) nd BF 3 etherte (5 ml) were dded to suspension of ulose monohydrte 28 2 (3.2 g, 8.9 mmol) in CCl 3 (30 ml). The mixture ws stirred for 5 min followed y dilution with CCl 3 (100 ml) nd onseutive wshings with 2 M N nd wter (3 30 ml). rying (N 2 S 4 ) nd evportion in vuo left syrup whih ws purified y elution from sili gel (3 30 m olumn) with 20:1 ylohexne/eta. Removl of the solvents from the produt-rrying frtions (R f = 0.57 in 2:1 ylohexne/eta) fforded 3.5 g (88%) of 29 s olourless syrup; ½Š 20 ¼ 121:4 ( 0.8, CCl 3 ). 1 NMR (300 Mz, MS-d 6 ): d 1.10 nd 1.24 (two 3-t, SEt-C 3 ), 2.70 (4-m, SEt-C 2 ), 3.72 nd 4.21 (two 1-dd, 5-2 ), 3.90 nd 4.07 (two 1-d, 1-2 ), 5.69 (1-ddd, 4-), 5.80 (1-d, 3- ); J 1,1 = 12.6, J 3,4 = 9.5, J 4,5 = 5.5 nd 9.5 z, J 5,5 = 10.5 z. 13 CNMR (75.47 Mz, MS-d 6 ): d 14.1 nd 14.2 (2 SEt-C 3 ), 22.4 nd 22.5 (2 SEt-C 2 ), 62.1 (C-2), 67.2 (C-5), 69.1 (C-4), 72.1 (C-1), 76.0 (C-3). Anl. Cld for C S 2 (446.6): C, 61.86;, Found: C, 61.76;, ,5-Anhydro--threo-pentulose diethyldithioetl 30 To ooled (0 C) 0.1 M N/ solution (100 ml) ws dded 5.5 g (12.3 mmol) of dienzote 29 nd the mixture ws stirred for 3 h t this temperture followed y neutrliztion with n idi resin (owex 50, + form). Filtrtion nd evportion in vuo left syrup whih ws dissolved in wter (50 ml). Wshing with ether (2 5 ml), evportion to dryness nd purifition of the syrupy residue y elution from sili gel ( m) with 20:1 C 2 Cl 2 /EtA gve 2.8 g (95%) of uniform (TLC) morphous produt, whih upon freeze drying of n queous solution rystllized; mp C; ½Š 20 ¼ 79:3 ( 1.1, ). 1 NMR (300 Mz, MS-d 6 ): d 1.13 nd 1.14 (two 3-t, SEt, C 3 ), 2.72 (4-m, SEt- C 2 ), 3.02 (1-m, 4-), 3.41 (1-dd, 3-), 3.46 nd 3.76 (two 1d, 1-2 ), 3.80 (2-m, 4-, 5-), 5.01 nd 5.40 (two 1-d, 2 ); J 1,1 = 12.2, J 3,4 = C NMR (75.47 Mz, MS-d 6 ): d 14.2 nd 14.4 (2 SEt-C 3 ), 21.8 nd 22.6 (2 SEtC 2 ), 64.1 (C-2), 67.7 (C-4), 71.1 (C-5), 73.3 (C-1), 79.8 (C-3). Anl. Cld for C S 2 (238.4): C, 45.35;, Found: 45.18;, Benzoyloxy-2-pyrn-3(6)-one 31 A few drops of pyridine were dded to solution of 680 mg (2 mmol) of ulose dienzote 29 in CCl 3 (10 ml) nd the mixture ws heted t reflux for 10 min. Evportion to dryness nd rerys-

9 960 P. Jrglis et l. / Tetrhedron: Asymmetry 20 (2009) tlliztion of the residue from methnol gve 560 mg (82%) of 31 s olourless needles; mp C. 1 NMR (300 Mz, CCl 3 ): d 4.32 (2-s, 2-2, 4.61 (2-d, 6-2 ), 4.61 (1-t, 5-); J 5,6 = 4.0 z. MS (F): m/e = 218 (M + ). Anl. Cld for C (218.2): C, 66.05;, Found: C, 66.01;, ,4-6-Tri--etyl-1,5-nhydro--sorose E-oxime 35 A solution of hydroxylmine hydrohloride (2.50 g) nd of syrupy 2-etoxy--gull triette (3.90 g, 11.8 mmol) in 30 ml of 1:1 pyridine/et ws mde to stnd for 6 h t mient temperture nd then stirred into wter (300 ml) followed y extrtion with CCl 3 (3 50 ml) nd onseutive wshings of the omined extrts with 2 N Cl (3 50 ml), wter (50 ml) std NCl 3 solution (50 ml) nd wter (50 ml). rying (N 2 S 4 ) nd evportion to dryness in vuo left 3.40 g (95%) of solid residue whih y 1 NMR proved to e 4:1 mixture of E nd Z isomers. Chromtogrphy on sili gel olumn (3 40 m, elution with 10:1 C 2 Cl 2 /EtA) nd proessing of the first produt-rrying frtion gve syrup upon evportion in vuo whih grdully rystllized on drying t 0.01 Torr overnight: 2.85 g (80%) of E- oxime 35; mp C; ½Š 20 ¼ 15:1 ( 0.6, CCl 3). 1 NMR (300 Mz, MS-d 6 ): d 2.03, 2.09 nd 2.10 (three 3-s, 3 A- C 3 ), 3.96 (1-m, 5-), 4.11 (2-m, 6-2 ), 4.01 nd 4.95 (two 13.1 z-d, 1 eh, 1-2 ), 5.00 (1-dd, 4-), 5.23 (1-d, 3-), (1-s, N): J 1,1 = 13.1, J 3,4 = 3.2 z. 13 C NMR (75.47 Mz, MS-d 6 ): d 59.1 (C-1), 62.6 (C-6), 67.9 nd 68.6 (C-3 nd C-4), 71.8 (C-5), (C-2). MS (F): m/e = 304 (M+1), 303 (M + ). Anl. Cld for C N 8 (303.26): C, 47.52;, 5.65; N, Found: C, 47.60;, 5.60; N, The frtions eluted next ontined the E/Z isomers in vrying ompositions s evidened y 1 NMR, the Z-oxime eing lerly differentited y shifts of -3 from 5.23 (E-form) to 6.03 nd one of the -1 protons from 4.95?4.37 ppm ,4-6-Tri--etyl-1,5-nhydro--psiose E-oxime 36 A mixture of hydroxylmine hydrohloride (2.1 g, 20 mmol), pyridine (10 ml), Et (10 ml) nd 3.30 g (10 mmol) of 2-etoxy--lll triette 33 11,12 ws stirred for 6 h t mient temperture nd susequently poured into wter (300 ml). Extrtion with CCl 3 (3 50 ml), nd onseutive wshings of the omined extrts with 2 M Cl, wter, std NC 3 solution nd gin wter, drying (N 2 S4) nd removl of the solvent in vuo left 3.0 g of rystlline produt, whih ws rerystllized from Et: 2.48 g (82%) of 36; mp C; ½Š 20 ¼þ27:2 ( 0.84, CCl 3). 1 NMR (300 Mz, MS-d 6 ): d 1.98, 2.01 nd 2.10 (three -s, 3 A-C 3 ), 4.00 (1-m, -5), 4.02 (1-d, -1), 4.17 (2-m, 6-2 ), 4.84 (1-dd, 4-), 4.91 (1-d, -1e), 5.71 (1-d, -3), (1-s, N); J 1,1 = 14.5, J 3,4 = 3.5, J 4,5 = 8.9 z. 13 C NMR (75.47 Mz, MS-d 6 ): d 20.3, 20.4, 20.5 (3 A-C 3 ), 59.6 (C-1), 62.7 (C-6), 68.1 nd 68.6 (C-3, C-4), 72.7 (C-5), (C-2). MS (F): m/e = 304 (M+1), 303 (M + ). Anl. Cld for C N 8 (303.26): C, 47.52;, 5.65; N, Found: C, 47.30;, 5.55; N, ,6-i--etyl-4--(2,3,4,6-tetr--etyl--gluopyrnosyl)-1,5-nhydro--frutose E-oxime 37 To solution of N 2. Cl (620 mg, 1 mmol) in pyridine (10 ml) ws dded 620 mg (1 mmol) of 2-etoxy-elloil hexette nd the mixture ws stirred t mient temperture for 7 h, susequently diluted with wter (10 ml) nd extrted with CCl 3 (3 10 ml). The omined CCl 3 extrts were wshed with wter, dried (N 2 S 4 ) nd tken to dryness in vuo. The syrupy residue rystllized on triturtion with ethnol: 430 mg (87%) of 37; mp C; ½Š 21 ¼ 22:3 ( 0.3, CCl 3); R f = 0.31 (enzene/eta 10:1). 1 NMR (300 Mz, MS-d 6 ): d = 1.99, 2.01 nd 2.03 (3s, 18, 6 A-C 3 ), 4.03 (15.1 z-d, 1, 1-), (5-m, 5-, 6-2,6 0-2 ), 4.91 (15.1 z-d, 1-e), (5-m, 4-, through 4 0 -), 6.80 (1-d, 3-), 11.4 (14-s, N). Anl. Cld for C N 16 (494.51): C, 58.29;, 6.52; N, Found: C, 58.17;, 6.48; N, Aknowledgements ur thnks re due to Priv.oz. r. Reinhrd usinger for luid disussions on NMR topis nd to the eutshe Forshungsgemeinshft for support of this reserh. Referenes 1. Brehm, M.; Gökel, V..; Jrglis, P.; Lihtenthler, F. W. 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