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U se of Tin and Other Metal Alkoxides1592 T he oxygen atom of metal alkoxides exhibits enhanced nucleophilicity due to the electropositive character of the metal. If the metal - o xygen bond is chemically labile, then the alkoxide should function well as a nucleophile. Tin alkoxides, especially organotin(IV) alkoxides, are extremely useful because the tin - o xygen bond is readily formed, thanks to its thermodynamic stability, while this bond is reactive enough to attack electrophiles. Because of its mildness and high selectivity, this procedure has found a wide range of applications, particularly in sugar chemistry, and this subject is therefore addressed in this chapter.B u 3S nOMe undergoes exothermic reaction with acid anhydrides and halides to give the corresponding esters [711] . This reactivity of Bu 2S nO is utilized for the selective acylation of nucleosides (Scheme 2.1 )[712] .The 2 ′,3 ′-O -(dibutylstannylene) nucleosides are obtained by heating a methanolic suspension of the nucleosidesand an equimolar amount of Bu 2 S nO. It is postulated that Bu 2S n(OMe) 2 is initiallyformed under these conditions. Treatment of the stannylene nucleosides with acetic or benzoic anhydride or chloride results in selective acylation at the 3 ′ - position, no acylation taking place on the primary alcohol. The stannylene inter-mediate does not need to be isolated, resulting in a one - p ot acylation: the additionof 5 – 10 equiv. of Ac 2 O and Et 3N to a solution of the stannylene prepared in metha-nol effects selective monoacetylation.Esterifi cation. Methods, Reactions, and Applications. 2nd Ed. J. Otera and J. Nishikido Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 978-3-527-32289-3E xperimental Pro cedure [712] S c heme 2.1 2′,3 ′-O -(Dibutylstannylene)uridine: A suspension of uridine (488 m g, 2 m mol) and dibutyltin oxide (500 m g, 2 m mol) in methanol (100 m L ) is heated under refl ux for 30 m in, and the resulting clear solution is then evaporated to dryness and dried i n vacuo .The resulting crystalline residue (915 m g, 96%) is analytically pure and has m.p. 232 –234 °.3′-O - B enzoyluridine: A solution of 2 ′,3 ′-O -(dibutylstannylene)uridine (2 m mol) in methanol (100 m L) is prepared i n situ as above. Triethylamine (1.4 m L, 10 m mol) and benzoyl chloride (1.2 m L, 10 m mol) are added, and the mixture is stirred at room temperature for 10 m in, at which point TL C (ethyl acetate/acetone 1 : 1) shows no remaining uridine. The solvent is evaporated i n vacuo and the residue is partitioned between ether (100 m L) and water, and fi ltered. The aqueous phase160 2Use of Tin and Other Metal AlkoxidesOHO OHBHOBu2Sn(OMe)2Bu 2SnO + MeOHOO OH B HOBu 2SnOMeOO O BHOSn Bu Bu3OBzO OHBHOcan be isolatedB= Ur, Cy, Ad, HxS cheme 2.1 is concentrated to about 30m L and allowed to crystallize. Recrystallization from aqueous ethanol gives pure (NMR and TLC) 3 ′-O -b enzoyluridine (570 m g, 78%) as the dihydrate.M ethyl α-D- h exopyranosides undergo selective acylation at the 2 - p osition by the stannylene method [713] .While 4,6 -O -b enzylidene D -h exopyranosides are con-verted into the corresponding stannylene derivatives, which undergo acylation at the 2 - p osition upon treatment with acyl halides in dioxane in the presence of Et 3N , the unprotected sugars are also successfully transformed into the C2 monoesters in one - p ot fashion without isolation of the stannylene intermediates (Scheme 2.2 ).The C2 esters of methyl α-D -g luco -,α-D -a llo -,and α-D-g alactopyranosides are obtained by this procedure.E xperimental Pro cedure S c heme 2.2 [713] M ethyl 2,3 -O -D ibutylstannylene -α -D -g lucopyranoside: Dibutyltin oxide (12.50 g , 50 m mol) is added to a solution of methyl α-D -g lucopyranoside (9.7 g , 50 m mol) in methanol (200 m L), and the resulting milky solution is heated at refl ux until it becomes homogeneous and clear (45 m in). After further heating at refl ux for an additional 0.5 h , the solvents are evaporated i n vacuo to leave a white solid, m.p. range 105 –115 °C . M ethyl 2 -O -B enzoyl -α - D -g lucopyranoside: Triethylamine (1.54 m L , 11 m mol) is added to a magnetically stirred, slightly cloudy solution of methyl 2,3 - O -2 Use of Tin and Other Metal Alkoxides161Me OHO MeHOMeMeOCH3 HOMeOHMeOHOMeOMeMeOCH3OMeOHBu2SnOSnBuBu PhCOClNEtMeOHOMeHOMeMeOCH3BzOMeOHS cheme 2.2OOHHOHOHOOMe32OOHHOHOOOOOR4R3OR2OR1OOMeMeBu3SnR1= R4= Bz, R2= R3= H (81%)R1= R2= R4= Bz, R3= H (18%) S cheme 2.3d ibutylstannylene -α-D-g lucopyranoside (4.25 g, 10 m mol) in dioxane (75 m L),followed by slow addition of benzoyl chloride (1.32 m L, 11 m mol). The solutionbecomes clear upon addition of the benzoyl chloride, but a white precipitate startsto form after about 2 m in. TLC examination of the solution (ethyl acetate, silica gelG) after 1 h shows the presence of a major spot at R f0.50 and a minor spot at R f0.70. The salts are fi ltered off and washed with dioxane (20 m L), and the combinedfi ltrates are evaporated i n vacuo to leave a syrup. This is fractionated on a columnof silica gel G (120 g) with ethyl acetate as eluent. The fi rst compound eluted fromthe column is methyl 2,6 -d i -O-b enzoyl -α-D-g lucopyranoside (0.08 g, ∼2%). Thesecond compound eluted from the column is the desired material (2.05 g, 70%).E xperimental Pro cedure S c heme 2.3 [714]M ethyl α-D-g lucopyranoside(283 m g, 1.46 m mol) is stannylated with (Bu 3S n) 2O(1.3 g, 2.19 m mol) in toluene(23 m L). A solution of benzoyl chloride (600 m g, 4.4 m mol) in toluene (5 m L) isthen added dropwise to the cooled solution over 5 m in at −10 °C. The mixtureis stirred for 4 h at −10 °C and then left for 17 h at −5°C. Acetic acid (0.2 m L) isadded and the solvent is evaporated i n vacuo to give an oily residue, which istriturated with diisopropyl ether to afford the crystalline product (588 m g, 95%).R egioselective acylation of sugars through the use of (Bu 3S n) 2O is also feasible[714] . In this case, the selectivity is governed by a monoalkoxytin intermediate coordinated by the proximate hydroxy group. For example, stannylation of methylα-D-g lucopyranoside with two equiv. of (Bu 3S n) 2O followed by treatment withbenzoyl chloride at 20 °C provides the 2,6 -d i -O-b enzoyl ester (81%) and the 2,3,6 -t ri -O-b enzoyl ester (18%) (Scheme 2.3 ). When the reaction is conducted at −10 °to−5°C,the dibenzoate is obtained in 95% yield.162 2 Use of Tin and Other Metal AlkoxidesThe regioselectivity in monoacylation of secondary hydroxy groups in monosac-charides can be controlled by the stannylene technique (Scheme 2.4 ) [715] . Use of one equiv. of strong base such as N - m ethylimidazole results in the formation of the equatorial 3 - b enzoate in a yield of more than 90%.OOPhHO OMeOH OO OPhBzOOMeOH Bu 2SnOOO O PhOOMeOSnBu BuBzClN-methylimidazole benzene> 90%S cheme 2.4 OO OO O O BEt 2BEt 2BEt 2Et 2BEt 2BEt 2B OHBzO OHOH HOOH +1. Bu 3Sn(acac)3. MeOHBzClS cheme 2.5 E xperimental Pro cedure S c heme 2.5 [716] A solution of hexa -O -d iethylboryl derivative (234 m g, 0.4 m mol) in toluene is treated with tributyltin acetylaceto-nate (0.5 m mol), and N - m ethylimidazole and benzoyl chloride are then added at −5°C . The reaction mixture is stirred at 5 °C for 10 h . After conventional workup the mixture is purifi ed by column chromatography on silica gel (chloroform/methanol, 3 :1). S elective O - a cylation and - a lkylation are feasible, as shown in Scheme 2.6 [717] and Scheme 2.7 [718] . B orylated carbohydrates are quantitatively O -s tannylated by transmetalation with tributyltin acetylacetonate. This methodology is applicable to O -a cylation of m yo -i nositol (Scheme 2.5 )[716] . The standard stannylene procedure is not effective for acylation because of the poor solubility of the stannylene intermediate, whereas the hexa -O - d iethylboryl derivative prepared by treatment with excess Et 3 B is soluble in hexane, and treatment of this compound with tributyltin acetylacetonate furnishes a partially borylated - s tannylated intermediate. Treatment of this com-pound with benzoyl chloride in the presence of N -m ethylimidazole affords 1 -O -b enzoyl -m yo -i nositol.2 Use of Tin and Other Metal Alkoxides 163OHOHOH OH OH OBn OBnOAc OAc OAc233. Ac 2O, PyS cheme 2.6 OPhHOHOOMeBu 2SnO,Bu 4NBrBrNO 2+O O O PhHOROOMeO O O Ph ROHOOMe+2O,PyO OO PhAcOROOMeR=2-NO 2C 6H 4CH 2S cheme 2.7 R OH ROHBu 2SnO, tolueneMS 4A, refluxOSnBu 2O R RR OCOR'ROHR'COClR'=R= OCOMe (80%; 90% de )R= Ph (69%; 8% de )S cheme 2.8 OH OH OHO OOHBu 2SnO, CH2Cl 2MS 4ASnBu 2R*COClOCOR*OH OHR*=OHO O**Z*S cheme 2.9 The use of chiral acid halides in the stannylene approach allows asymmetric acylation of m eso -1,2 -d iols. Thus, treatment of m eso -d imethyl tartrate with Bu 2S nO followed by (1 S ) - k etopinic acid chloride exclusively affords the monoacylation product in high yield and with high diastereoselectivity (Scheme 2.8 ) [719] .Optically active glycerol acetonide can be prepared analogously from achiral glycerol (Scheme 2.9 )[720] .164 2 Use of Tin and Other Metal AlkoxidesE xperimental Pro cedure S c heme 2.10 [721] S odium carbonate (1.5 m mol)base is suspended in HF (5 m L) containing racemic alcohol (1 m mol), water (100 µl, 5.5 m mol), and organotin catalyst (0.25 m ol%). Benzoyl chloride(0.5 m mol) is then added to the suspension at −10 °C, and the resultingsolution is stirred at that temperature for 14 h. After conventional workup, a mixture of primary monobenzoate (86% e e, 38% yield) and recovered racemic alcohol (46% e e, 58% yield) is obtained, with a trace amount of secondary monobenzoate.PhOHOHcatalyst,Na2CO3THF / H2O+BzCl+PhOHOBzPhOHOH+(±)2catalyst=S cheme 2.10W hen the treatment of unsymmetrical diols by the stannylene procedure isaccompanied by i n situ quenching with chlorosilane or oxalic acid, acylation takesplace on the more substituted hydroxy group (Scheme 2.11 )[722, 723] . Thismethod can be applied to 1,2 -,1,3 -,and 1,4 -d iols of primary -s econdary, primary -t ertiary, and secondary -t ertiary natures. Benzoyl chloride and other acid chloridesare employable, but acid anhydrides are of no use.E xperimental Pro cedure S c heme 2.11 [723] G eneral Acylation Procedure: Aportion of the diol (1.5 m mol) is dissolved or suspended in toluene (30 m L),and, after the addition of dibutyltin oxide in 5% molar excess, water is separatedby azeotropic distillation in a Dean -S tark apparatus for a variable length oftime, depending on the substrate. After evaporation of the solvent, the residueis dried under vacuum, dissolved under nitrogen in anhydrous CHCl 3(30 m L), and cooled to 0 –5°C. An equimolar amount of the appropriate acylat-ing reagent in the same solvent (1 m L) is added dropwise to the stirred solutionby syringe through a septum cap, and the reaction mixture is allowed to reactat room temperature for 1 h, and then quenched by one of two differentmethods.K inetic resolution of chiral 1,2 -d iols is effected by use of an organotin catalystwith a binaphthyl moiety as a chiral source (Scheme 2.10 )[721] . Addition ofsodium carbonate and a small amount of water improves the selectivity.2 Use of Tin and Other Metal Alkoxides 165ROH (CH 2)n OH+Bu 2SnOtolueneRO(CH 2)n OSnBu 21. R'COCl, CHCl 32. Me 3SiCl or (COOH)2R OCOR'(CH 2)n OSiMe 3ROSiMe 3(CH 2)n OCOR'+(or OH)(or OH)63 : 37~98 : 2S cheme 2.11 M ethod A – Quenching with Trialkylsilyl Chlorides: A solution of the appropri-ate silyl chloride (5% molar excess) in anhydrous CHCl 3(1 m L) is added dropwise by syringe to the cooled solution (0 – 5 ° C ), and the mixture is then allowed to reactat room temperature for 1 – 2 h . The mixture obtained is then analyzed by1H NMR spectroscopy. M ethod B – Quenching with Oxalic Acid: The solvent is evaporated undervacuum, and the residue is dissolved in anhydrous CH 3C N (8 m L). The solution is cooled to 0 –5°C , oxalic acid (0.75 m mol) in CH 3C N (3.5m L) is added, and the mixture is stirred at room temperature for 20 h . The resulting suspension is fi l-tered under nitrogen, and the solid is washed several times with CH 3C N. The residue obtained after evaporation of the solvent under vacuum is dissolved inCDCl 3 , and the mixture is analyzed by 1H NMR spectroscopy. Microwave irradiation is useful not only for shortening the time required to prepare the stannylene intermediates but also for rendering the procedure cata-lytic. As shown in Scheme 2.12 , if Bu2S n(OH)Cl is successfully transformed to non-selective benzoylationBu 2SnOOOSnBu 2BzCl,baseSnBu 2ClBu 2Sn(OH)Clbase,S cheme 2.12166 2 Use of Tin and Other Metal Alkoxides(CH2)n R OH R'OH +BzCl(CH2)nR OBzR'OH0.01~0.1eq.Me2SnCl22 eq.K2CO3,rtS cheme 2.13HOOH(CH2nO O2n= 3 (42%)n= 4 (28%)n= 5 (35%)n= 6 (35%)n= 7 (53%)n= 8 (65%)CH2CH2OBu2SnBu2OOCH2CH23)n S cheme 2.14Bu 2S nO in the presence of a base, the organotin species can be recycled. Under normal conditions, however, in which heating is necessary to prepare stannylate diols, the base promotes the reaction between benzoyl chloride and diols. However, no such direct reaction occurs under microwave conditions, thus allowing the catalytic cycle to complete.T he catalytic process is also achievable through the use of Me 2S nCl 2in the pres-ence of K 2C O 3, although the mechanism is not clear (Scheme 2.13 )[724] . A variety of cyclic and acyclic diols, 1,2 -d iols in particular, are selectively monobenzoylated in good yield.E xperimental Pro cedure S c heme 2.13 [724] A catalytic amount of dimethyltin dichloride (0.01 m mol), solid K 2C O 3(2.0 m mol), and benzoyl chloride (1.2 m mol) are successively added at room temperature to a THF (5 m L) solution of t rans-1,2 -c yclohexanediol (1 m mol). After the mixture has been stirred at room tem-perature until t rans-1,2 -c yclohexanediol has disappeared (checked by thin layer chromatography), the mixture is poured into water and the organic portion is extracted with CH 2C l 2. After evaporation of the solvent, a residue is obtained, and this is confi rmed by NMR to be pure monobenzoylated product ( >99%).C yclic stannoxanes made up of dibutylstannylene and 1, n -d ialkoxy units func-tion as covalent templates in reaction with acid dihalides to give macrocycles (Scheme 2.14 )[725, 726] . Acid anhydrides are also employable, and the use of chiral tin templates affords diastereomeric macrocyles (Scheme 2.15 )[727, 728] . N-(Trifl uoroacetyl) -g lutamic and -a spartic anhydrides provide macrocylces with an2 Use of Tin and Other Metal Alkoxides 167+Bu 2Sn(OEt)2O SnBu 2O Me(±)HOOHMeClOO )5Me HC MeOO SnBu 2OOBu 2Sn MeMedimeric complexes of stannoxanesS cheme 2.15 O O OHNF 3CO Bu 22+CH 2CH 2O CO CHF 3COCHN CH 2OCO HC NHCOCF 3CH 2CH 2CH 2OOOOCHCl 3 (boiling)S cheme 2.16 O 2CH O Bu 2SnSnBu 2OO2CH O O O ONMeor +OO O orS cheme 2.17 amino residue on the ring (Scheme 2.16 ). Treatment of the distannoxane with a cyclic carboxy - c arbonate derived from glycolic acid or isatoic anhydride results in ring opening (Scheme 2.17 )[729] . T in(II) alkoxides are also effective. Reactions between 1,1 ′-d imethylstannocene and alcohols readily occur at room temperature, and the resulting tin(II) alkoxides168 2 Use of Tin and Other Metal Alkoxidesprovide esters upon treatment with acid halides (Scheme 2.18 ) [730] . When this reaction is carried out in the presence of a chiral amine ligand, asymmetric desym-metrization of 2 - O - p rotected glycerols is feasible, furnishing monoesters with up to 84% e e (Scheme 2.19 )[731] .+SnR'COCl, toluene R'COOR 60~94%ROHS cheme 2.18 SnCl+R=Ph,o -ClC 6H 4,1-naphthyl,PhCH=CH,cHexS cheme 2.19 E xperimental Pro cedure S c heme 2.18 [730] 3-P henylpropanol (125 m g, 0.921 m mol) in toluene (1.5 m L) is added at room temperature, under an argon atmosphere, to a toluene solution (2 m L) of 1,1 ′-d imethylstannocene (153 m g, 0.552 m mol). After the mixture has been stirred for 30 m in, hexamethylphos-phoric triamide (1 m L ) and benzoyl chloride (155 m g, 1.11 m mol) in toluene (1.5 m L) are successively added. The mixture is kept stirring at room tempera-ture for 2 h and quenched with pH 7 phosphate buffer. The aqueous phase is extracted three times with ether and the combined extracts are washed withbrine and dried over anhydrous Na 2S O 4. After evaporation of the solvent, the resulting crude product is purifi ed by silica - g el thin layer chromatography to afford 3 -p henylpropyl benzoate (200 m g, 90%). T he stannylene technique has been successfully applied to synthesis of ( – ) - i nte-gerrimine (Scheme 2.20 )[732] and ( –)-s enecionine (Scheme 2.21 )[733] .M etallacycles with metals other than tin also react with acid halides. When an arsole or a stibole is treated with one equiv. of acid halides with subsequent hydrolysis, a monoester is produced (Scheme 2.22 ) [734] . On the other hand, treatment with two equiv. of acid halides affords the corresponding diesters.2 Use of Tin and Other Metal Alkoxides169NOHHOH Bu 2SnO, benzene NOH OSn Bu Bu OOOMe OCH 2SCH 3MeHNOH benzene, 5°COO OH Me H OCH 2SCH 3MeN OO HOO Me HOH Me (-)-IntegerrimineHOS cheme 2.20 OOCH 2SCH 3HBu 2SnO, MSbenzeneNHOOHHNOH OBu 2Sn OH OHOOC MeHOCH 2SCH 3MeN OOH OOHMeOMe H(-)-SenecionineS cheme 2.21 OMCl O R R'RR'ROCOR''R'OMCl 2OCOR''OCOR''H 2OR OCOR''R'OHM= As, SbS cheme 2.22170 2 Use of Tin and Other Metal AlkoxidesCl(CH 2)nOClO RR OSb OCl benzene, reflux OO RR OO(CH 2)n (CH 2)n O O O ORR18~36%n= 1, 3, 5, 7, 8S cheme 2.23 O R H H PhO O OR AcOH OHH PhOOR HO H OAcH PhO OR AcOH OAcH Ph+++2 eq. NaH, THF 2ChiralChiralChiralChiral a: R= SC 2H 5 (74%)b: R= SePh (81%)c: R= OPh (63%)a: 0%b: 0%c: 19%a: 21%b: 3%c: 0%AcClS cheme 2.24 Macrocyles can be obtained by the treatment of stiboles with diacid dihalides (Scheme 2.23 )[735] . C opper(II) also functions as a template. Regioselective C3 O - a cylation is achieved by treatment of sodium salts of 4,6 - O -b enzylidene -g lucopyranosides (prepared byaddition of NaH) with CuCl 2 followed by acid halides (Scheme2.24 ) [736] . S i(OMe) 4 acts as a catalyst/reagent in the selective methylation of 2 -h ydroxycar-boxylic acids (Scheme 2.25 ) [737] . 2 - H ydroxy acids play a crucial role: the hydroxy acid attaches to silicon through the alkoxy group and subsequently through the carboxy group in an intramolecular rearrangement to form an unstable and reac-tive cyclic intermediate. This intermediate may accelerate methylation of the car-boxylic acid via nucleophilic attack of MeOH at the carbonyl group. B(OBu) 3acts similarly for butylation of dicarboxylic acids (Scheme 2.26 ) [738] . Heating of a mixture of dicarboxylic acid and B(OBu) 3in a 3 :2ratio affords the desired diester in good yield.2 Use of Tin and Other Metal Alkoxides 171I n transesterifi cation, a tetranuclear zinc cluster, Zn 4(OCOCF 3)6 O , acylates alco-hols in the presence of free amine [739] , in contrast to the conventional reactivity, by which amines are more reactive than alcohols due to their stronger nucle-ophilicity. In this sense, the zinc cluster is similar to lipase. With this catalyst, various amino alcohols are transformed into the corresponding esters without violating the amine function (Scheme 2.27 ).Si(OMe)43O Si O X OOMeOMe -+O SiO X OOMe OMeO Si OOMe OMe -+MeOH-H O Si +MeOH++H +;-MeOH+OMe OHOMe -MeOHS cheme 2.25 3 HOOC 2B(OBu)33H 3BO 32++BuOOC Z COOHZ COOBuS cheme 2.26 Zn 4(OCOCF 3)6Oi -Pr 2O,reflux>82<18+:H 2N H 2N +Z OHZ OCOPhPhCONH Z OCOPhS cheme 2.27。
何首乌蒽醌类化学成分的提取和鉴别何首乌是常用补益中药, 来源于蓼科植物何首乌的干燥块根。
中医药认为, 何首乌味苦、涩, 性温。
归肝、心、肾经。
生用解毒消痈, 润肠通便; 制用补肝肾, 益精血, 乌须发, 强筋骨。
含游离蒽醌类衍生物约1.1%，大部分与葡萄糖结合成苷现代研究表明, 何首乌具有降血脂、延缓动脉粥样硬化、抗衰老、提高免疫力、益智等作用。
（王文静, 薛咏梅,等.何首乌的化学成分和药理作用研究进展[ J ].云南中医学院报，2007，1000—2723）,何首乌为蓼科植物何首乌Polygonum multiflo-rumThunb.的干燥块根,为常用中药。
现代研究发现何首乌含有二苯乙烯苷类、蒽醌类、黄酮类等多种成分[1],具有抗衰老、增强免疫力、抗菌、调血脂等多方面的药理作用[2]。
我国植物资源丰富,分布于东北、中南、华东、西南各省。
国内外学者对四川和广东产的何首乌进行了较多的研究,为了更好的开发和利用植物资源,进一步寻找活性成分,笔者对采自泰山的何首乌化学成分进行了系统的研究,从中得到9个蒽醌类化合物,分别鉴定为大黄素(emodin,Ⅰ)、大黄素甲醚(physcion,Ⅱ)、拟石黄衣醇(迷人醇,fallacinol,Ⅲ)、大黄素-8-甲醚(questin,Ⅳ)、桔红青霉素(emodin-6,8-dimethylether,Ⅴ)、ω-羟基大黄素(citreorosein,Ⅵ)、大黄素-8-O-β-D-吡喃葡萄糖苷(emodin-8-O-β-D-glucopyranoisde,Ⅶ)、大黄素-8-O-(6′-O-乙酰基)-β-D-吡喃葡萄糖苷[emodin-8-O-(6′-O-acetyl)-β-D-glucopyranoside,Ⅷ]和大黄素甲醚-8-O-β-D-吡喃葡萄糖苷(physcion-8-O-β-D-glucopyranoside,Ⅸ)。
化合物Ⅴ为首次从该科植物中分得,化合物Ⅲ和Ⅷ为首次从该种植物中分得。
![[精品]水母雪莲功效](https://img.taocdn.com/s1/m/b76a8dfb112de2bd960590c69ec3d5bbfd0ada26.png)
水母雪莲花汉语拼音 Shui mu xue lian hua蒙药名孟和-其其格别名札高德一苏格巴，查干-达吉德考证本品载于《晶珠本草》。
内称:“札高德-苏格巴生于雪山雪线附近碎石地带……茎中空，被绵状绒毛，生态状如曹日老贡，茎顶开花，花微紫红，状如秃骛蹲在岩石上。
”上述植物生境、形态特征与水母雪莲花之生境、形态相符，故认定历代蒙医药文献所载的和高德一苏格巴即益和一其其格（水母雪莲花)。
中药材基原为菊科植物水母雪莲花的带花全株。
动物矿物植物形态水母雪莲花 Saussurea medusa Maxim. 多年生草本，高10～20cm，全株密被白色绵毛。
茎短而粗。
叶密生，具长而扁的叶柄；叶片卵圆形、倒卵形，边缘有条裂状锯齿，齿尖急尖，上部叶成菱形、披针形，基部延伸成翅柄或否。
头状花序密集，无总梗，总苞球形，总苞片2～3层，膜质，线状长圆形不等长；花紫色。
瘦果，冠毛2层，灰白色，外层刺毛状，内层为羽状。
花期7～9月，果期8～9月。
生于高山砾石间。
分布于甘肃、青海、四川、云南、西藏等地。
栽培与养殖采收加工 6～7月间开花时，拔起全株，除去泥沙，晾干。
药材鉴别地上部分长8～15cm主根长约15cm。
根茎细长，有褐色残留叶柄。
基部叶倒卵形，上半部边缘有8～12个粗齿，基部楔形；上部叶渐小，卵形或卵状披针形，两面被白色绵毛；最上部叶条形或条状披针形，边缘有条裂或细齿。
花紫色或淡红色，冠毛白色，内层羽状。
化学成分本品地上部分含金圣草素-7-O-β-D-葡萄糖苷（chrysoeriol-7-O-β-D-glucoside)，芹莱素-7-O-β-D-葡萄糖苷（apigenin-7-O-β-D-glucoside)，木犀草素-7-O-β-D-葡萄糖苷（luteolin-7-O-β-D-glucoside)，芸香苷（rutin)［1］，木犀草素-7-O-α-L-吡喃鼠李糖基（1→2)-β-D-吡喃葡萄糖苷（luteolin-7-O-α-Lrhamnopyranosyl（l→2)-β-D-glucopyranoside］，芹菜素-7-O-α-L-吡喃鼠李糖（1→2)-β-D-吡喃葡萄糖苷［apigenin-7-O-α-L-rham-nonvranosvl（l→2)-β-D-glucopyranosid］,槲皮素-3-O-β-D-吡喃葡萄糖苷（quercetin-3-O-β-D-glucopyranosiode)，芹菜素（api-genin)，木犀草素（luteolin)，牛蒂苷（arctiin)［2］。
一种甲基膦酸二甲庚酯的放大制备方法与流程下载温馨提示:该文档是我店铺精心编制而成，希望大家下载以后，能够帮助大家解决实际的问题。
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救必应化学成分及其心血管药理作用研究进展摘要】救必应是一味取自铁冬青树皮的传统中药，现已分离出十多种提取物，具有抗肿瘤、抗细菌、抗炎等多种药理作用。
研究发现，对心血管系统，救必应及其提取物具有抗心律失常、缓解心肌缺血、降低血管压力、抑制心肌细胞凋亡、抑制氧化应激等作用。
本文对救必应的化学成分、心血管药理作用及其机制进行综述，为救必应治疗心血管疾病的临床应用提供参考。
【关键词】救必应；化学成分；心血管疾病；药理作用【中图分类号】R972 【文献标识码】A 【文章编号】2095-1752（2019）15-0010-02Research progress on chemical constituents and cardiovascular pharmacological effects of bark from Ilex rotunda ThunbZang Lichao, Xiao Xiangyu, Zhou Yunkai , Zhang Ting.College of Medical Technology, Zhejiang Chinese Medical University, Hangzhou Zhejiang 310053,China【Abstract】Ilex rotunda Thunb is a traditional Chinese medicine which is taken from the bark of Ilex rotunda Thunb.More than ten kinds of extracts have been isolated.They have many pharmacological effects such as anti-tumor, anti-bacterial,anti-inflammatory and liver protection.It is found that in the cardiovascular system,Ilex rotunda Thunb and its extracts could inhibit oxidative stress, reduce vascular pressure, inhibit cardiomyocyte apoptosis, relieve myocardial ischemia, and resist arrhythmia. This article reviews the chemical composition, cardiovascular pharmacological effects and mechanisms of Ilex rotunda Thunb, which lays a foundation of its clinical application.【Key words】Ilex rotunda Thunb;Chemical constituents;Cardiovascular disease;Pharmacological effects心血管疾病（cardiovascular diseases，CVD）是指原发或主要累及心脏和血管的疾病，为冠心病、高血压、脑血管的总称[1]。
合成2,3,4,6-O-四苄基-α-D-葡萄糖三氯乙酰亚胺酯的工艺改进傅大双;张首国;彭涛;温晓雪;颜海燕;王林【摘要】2,3,4,6-Tetra-O-benzyl-α-D-glucopyranosyl trichloroacetimidatein total yield of 44.2％ was synthesized from D-glucose bymethylation,benzyl protection,hydrolysis and then reaction with trichloroacetonitril.The structures were confirmed by 1 H NMR and ESI-MS.%以D-葡萄糖为起始原料,经甲基化、苄基保护和水解,再与三氯乙腈反应合成了2,3,4,6-O-四苄基-α-D-葡萄糖三氯乙酰亚胺酯,总收率44.2％,其结构经1H NMR 和ESI-MS确证.【期刊名称】《合成化学》【年(卷),期】2013(021)003【总页数】4页(P333-335,341)【关键词】D-葡萄糖;三氯乙酰亚胺酯;合成;工艺改进【作者】傅大双;张首国;彭涛;温晓雪;颜海燕;王林【作者单位】安徽医科大学研究生院,安徽合肥230032 ;军事医学科学院放射与辐射医学研究所,北京100850;军事医学科学院放射与辐射医学研究所,北京100850;军事医学科学院放射与辐射医学研究所,北京100850;军事医学科学院放射与辐射医学研究所,北京100850;军事医学科学院放射与辐射医学研究所,北京100850;军事医学科学院放射与辐射医学研究所,北京100850【正文语种】中文【中图分类】O629.112，3，4，6-O-四苄基-α-D-葡萄糖三氯乙酰亚胺酯(4)具有活性好、低温下结构稳定、立体选择性好等诸多优点，可用于合成硫苷［1，2］、氧苷［3，4］、碳苷［5，6］和氮苷［7］等，在糖类化合物和糖缀合物的合成中也有重要的作用。
1 黄芪的化学成分黄芪的化学成分众多, 主要含皂苷类、黄酮类、多糖类及氨基酸类等, 另外还含有蔗糖、黏液质、苦味素、胆碱、甜菜碱、叶酸等。
屠鹏飞等[ 2]对黄芪进行了较系统的化学成分研究, 到目前为止已分离得到32种化合物, 鉴定了其中的14种化合物, 包括4种异黄酮[芒柄花素( X-64)、芒柄花素-7-O--D葡萄糖苷( K-12-1)、毛蕊异黄酮( X-100-21)和毛蕊异黄酮-7-O-?-D葡萄糖苷], 2种异黄烷[ ( 3R) -8, 2"-二羟基- 7, 4*-二甲氧基异黄烷( X-66)、2", 3" 4"-三甲氧基异黄烷-7-O-?-D-葡萄糖苷], 1种紫檀烷[ ( 6aR, 11aR) 9, 10- 二甲氧基紫檀烷-3-O-?-D-葡萄糖苷( X-186) ], 1种皂苷[黄芪甲苷( h-29) ], 6种其它类成分[ ?-谷甾醇( E-191)、5-甲基- 呋喃甲醛( X-30)、5?甲氧基?2?吡咯甲醛( X-67)、1, 3, 5-三烯-1, 6-己二醇( E-32-10-17)、2, 4-二烯- 己二酸( E-32-19-14)和尿嘧啶核苷( h-33-7) ]。
其他化合物正在鉴定中。
图 1 黄芪的HPLC-APCI-MS（A）和HPLC-DAD（B）色谱指纹图谱Fig. 1 Chromatographic fingerprints of Astragali Radix by HPLC-APCI-MS (A) and byHPLC-DAD (B)表 1 黄芪HPLC-DAD-MS 指纹图谱中各色谱峰的保留时间、质谱和紫外光谱数据峰号t/min λmax/nm 质谱(m/z) 化合物1 17.336 258, 288 447, 285 calycosin-7-O-β-D-glycoside2 20.730 280, 325 2173 22.752 280, 325 2244 26.642 280, 325 489, 2855 30.390 250, 300 431, 269 ononin6 34.898 248, 288 285 calycosin7 40.733 230, 282 3018 44.394 250, 300 269 formononetin9 44.394 280 303 (3R)-7,2′-dihydroxy,4-dimethoxyisoflavone10 53.372 230 295, 293, 34811 55.662 –295, 227, 31112 61.692 –24513 62.250 –313, 295, 27714 64.555 –27915 65.001 –297, 279, 31516 65.483 –27917 65.884 –297, 279, 31518 66.585 –437, 455, 419 astragaloside IV19 67.312 –29320 67.562 280 361, 27721 68.126 230 27722 69.266 –35323 70.505 280 295, 29624 71.616 280 29525 74.030 230 2791 黄芪多糖蒙古黄芪的多糖研究已取得一定进展, 其多糖含量处于中上水平。
桃花类落叶小乔木桃花，桃树盛开的花，属于蔷薇科。
叶椭圆形、披针形，核果近球形，主要分为果桃和花桃两大类。
桃花起源于中国中部和北部，在世界温带国家和地区广泛种植。
它的繁殖主要靠嫁接。
形态特征桃花为落叶乔木。
叶椭圆状披针形，叶缘有粗锯齿，无毛，叶柄长1-2cm。
高可达3～10米。
通常有1至数枚腺体;叶片椭圆状披针形至倒卵状披针形，边缘具细锯齿，两面无毛。
花通常单生，生于叶开放，直径约2.5-3.5cm，具短梗;萼片5枚，基部合生成短萼筒，无毛。
叶柄长7-12mm，具腺点。
树干灰褐色，粗糙有孔。
小枝红褐色或褐绿色，平滑。
花单生，有白、粉红、红等色，重瓣或半重瓣，花期3-4月。
核果近圆形，黄绿色，表面密被短绒毛，因品种不同，果熟6～9月。
主要分果桃和花桃两大类。
变种有深红、绯红、纯白及红白混色等花色变化以及复瓣和重瓣种。
较重要的变种有：油桃、蟠桃、寿星桃、碧桃。
其中油桃和蟠桃都作果树栽培，寿星桃和碧桃主要供观赏，寿星桃还可作桃的矮化砧。
树高4～5米。
一年生枝条红褐色。
叶多呈披针形，叶缘有锯齿，叶柄基部常生蜜腺。
花型有蔷薇型和铃型两种。
核果除蟠桃外，多为圆形或长圆形，果面除油桃外，均布有茸毛。
果肉白，黄色或夹红晕，少数呈红色;肉质柔软、脆硬或密韧;核表面具不同沟点纹路，均为种和品种群的重要分类依据。
桃花是我国传统的园林花卉，是早春重要的观花树种之一，树形优美，枝繁叶茂，花色艳丽。
桃的果实是著名的水果;桃核可以榨油;其枝、叶、果、根俱能入药;桃木细密坚硬，可供雕刻用。
生长习性桃性喜光，要求通风良好;喜排水良好，耐旱;畏涝，如受涝3～5日，轻则落叶，重则死亡。
耐寒，华东、华北一般可露地越冬。
桃花宜轻壤土，水分以保持半墒为好。
不耐碱土，亦不喜土质过于粘重，不择肥料，其余生态习性大致与梅类似。
但生长势与发枝力皆较梅为强，而不能持久，约自20龄起即始趋衰退。
一般树龄可维持20～40年。
桃树进入花、果的年龄皆早，通常嫁接苗定植后1～2年即始花始果，3～5年进入花果盛期。
五味子五味子中其他成分的分析方法五味子为木兰科植物五味子的干燥成熟果实，习称“北五味子”。
北五味子主产地为辽宁、黑龙江、吉林等，本草中列为上品，认为有益气、明目、补不足、养五脏、壮筋骨的作用，且具有滋肾敛肺、生津收汗、涩精、安神之功能。
迄今为止，国内外学者在五味子的化学成分和药理作用、临床应用等方面均已取得一定研究成果，现结合国内外文献将五味子的化学成分研究进行汇总分析，以期对五味子的发药品及保健品有参考作用。
五味子中化学成分为挥发性成分、木脂素类、有机酸类、多糖类、苷类、其他成分等。
一．化学成分1.挥发性成分五味子中挥发性成分主要成分为萜类化合物，另外还含有少量的醇、酯、醛、酮以及苯和奈的衍生物等，主要为α-蒎烯（α-pinem ）、茨烯（camphene ）、β-蒎烯（β- pinem ）、月桂烯（myrcene ）、α-萜品烯（α-terpinene ）、柠檬烯（limonene ）等。
周英等报道，从五味子属植物中分离鉴定了200个成分，其中包括34 个三萜类成分。
秦波等报道，五味子挥发油含有单萜类、含氧单萜类、倍半萜类、含氧倍半萜类和少量醇、酸等含氧化合物。
芮和恺等从五味子挥发油中鉴定了29 中化合物，站挥发油总量的39.65%，除澄茄烯、依兰烯、防风根烯外，其余成分均属首次从五味子挥发油中发现，包括倍半蒈烯、α-花柏醇等。
刘风雷等用气相色谱法测定北五味子油中亚油酸的含量为12.1%，12.7%和13.0%。
戴好富等对辽宁北五味子的干燥果实经水蒸气蒸馏得到其挥发油并对其中的化学成分进行GC-MS 定性定量分析，共检出81个组分，鉴定了其中的5O个化合物。
李晓宁等。
2.木脂素类我国学者先后从北五味子中分离出五味子甲素(shiandrin A)、五味子乙素(shiandrin B)、五味子丙素(shiandrin C)、五味子醇甲(sehizandrol A)、五味子醇乙(sehizandrol B)、五味子酯甲(wuweizi ester A)、五味子酯乙（wuweizi ester B)等化合物。
Monatsh Chem139,525–535(2008)DOI10.1007/s00706-007-0799-7Correspondence:Pe´ter Bako´,Department of Organic Chem-istry and Technology,Budapest University of Technology and Economics,1521Budapest,P.O.Box91,Hungary.E-mail: pbako@mail.bme.hutransfer catalysts in certain types of asymmetric reactions[7].Valuable information has been collect-ed on the structure–enantioselectivity relationship. Regarding the carbohydrate moiety anellated to the azacrown ring,the glucopyranoside unit seemed to be more efficient than the galactopyranoside,man-nopyranoside,altropyranoside and mannitol moie-ties[8].Among the alkyl-,alkoxy-,aralkyl-,and other(e.g.,P-functionalized)N-substituents,the hydroxypropyl-,and in same cases,the methoxypro-pyl side arm was the most advantageous from the point of view of enantioselectivity.In these cases, the sugar moiety was protected by a4,6-O-ben-zylidene group.The asymmetric induction brought about by macrocycles incorporating a methyl-4,6-O-benzylidene- -D-glucopyranoside unit(1a and1b) has been thoroughly studied utilizing suitable model reactions[7,8].4,6-Di-O-butylether derivatives have also been investigated as chiral catalysts[9].The question emerged,how the change or elimi-nation of the benzylidene group in macrocycles1 may influence the catalytic properties,especially the enantioselectivity.In this paper,a number of new lariat ethers are introduced,where the4-and6-hydroxy groups of the -methyl-glucopyranoside unit are free or protected in the form of acetals. The resulting species are(1-naphthyl)methylene-or isopropylidene derivatives.Results and discussionSynthesisOne of the starting materials,methyl-4,6-O-(1-naphthyl)methylene- -D-glucopyranoside(6)was prepared by the reaction of methyl- -D-glucopyrano-side and1-naphthaldehyde dimethyl acetal(5)in DMF,in the presence of camphorsulfonic acid as the catalyst.The crystalline dioxane-type acetal(6)was obtained in58%yield.The equatorial position of the naphthyl-substituent was substantiated on the basis of the1H NMR spectrum and an analogy;the2-naphthyl-methylene acetal analogue is a known compound[10]. The starting1-(dimethoxymethyl)naphthalene(5)was obtained in the reaction of1-naphthaldehyde with trimethyl orthoformate in dry methanol in the presence of anhydrous zinc chloride catalyst.The other starting sugar derivative,methyl-4,6-O-isopropylidene- -D-glucoside(9)was synthesized by the reaction of methyl- -D-glucopyranoside and 2,2-dimethoxypropane in acetone,using catalytic amounts of2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ)in70%yield[11].Establishment of the crown ring in the2and3position of the glucopyra-noside acetals(6and9)was accomplished in three steps,as described earlier[6,12].The vicinal hydroxy groups of6and9were alkylated with bis(2-chloro-ethyl)ether in the presence of tetrabutylammonium hydrogen sulfate and50%aq.NaOH in a liquid–liquid two-phase system to give intermediate7and 10which were purified by chromatography.The ex-change of chlorine to iodine in intermediates7and 10was accomplished in reaction with NaI in boiling acetone to afford bis-iodo derivative8and11,pounds8and11were then cyclized with two kinds of primary amines,such as3-aminopropanol and3-methoxypropylamine,in boiling acetonitrile,in the presence of sodium carbonate to afford after puri-fication by column chromatography azacrown ethers 2a–2b and3a–3b,respectively.The yield of cycliza-tions reactions was40–47%(Scheme1).The benzylidene protecting group in compounds 1a–1b was removed by catalytic hydrogenation to give lariat ethers4a–4b with free hydroxy groups in positions4and6.All intermediates and new products were charac-terized by1H,13C NMR and mass spectroscopy. Asymmetric inductionChiral crown ethers2a–2b and3a–3b were tested in a Michael addition,a Darzens condensation and an epoxidation reaction.In all cases,the products were isolated by preparative TLC after the usual work-up procedure.The enantiomeric excess(ee=%)was de-termined by measuring the optical rotation of the products or by1H NMR spectroscopy using(þ)-Eu(hfc)3as a chiral shift reagent.Michael addition of2-nitropropane to chalcone The stereoselective variants of the addition of enolates or their analogues to the carbon–carbon double-bond of the , -unsaturated ketones or alde-hydes have been extensively investigated in recent years[13].Perhaps,the most frequently studied model reaction is the Michael addition of methyl phenyl acetate to methyl acrylate carried out in the presence of a sugar-based crown ether,with which enantioselectivities of53–70%were detected[14].526 A.Mako´et al.Asymmetric induction due to glucose-based azacrown ethers(1)in the Michael addition of2-nitropropane to chalcone was observed earlier[7, 9].In the present study,the effect of glucose-based macrocycles2a–2b,3a–3b,and4a–4b was studied in the same model reaction.The solid-liquid phase transfer catalytic reaction was carried out at room temperature in dry toluene,in the presence of solid sodium tert-butylate(35mol%) and one of the chiral catalysts prepared(7mol%) (Scheme2).The experimental data are shown in Table1.It can be seen that the substituent in positions4 and6of the catalyst and the side arm on the nitrogen atom of the ring have a significant influence on the asymmetric induction.While the use of4,6-O-ben-zylidene derivatives as catalysts lead to ee values of 85and87%for the lariat ethers with hydroxypro-pyl and methoxypropyl side arms(1a and1b,re-spectively),the application of1-naphthylmethylene derivatives2a and2b resulted in ee values of90 and68%(entries3and4).It can be seen that the N-hydroxypropyl substituent was more favorable. Regarding the isopropylidene derivatives,the eeof Reagent and condition:(i)O(CH2CH2Cl)2,50%aq.NaOH,N Bu4HSO4,rt;(ii)NaI,acetone,reflux;(iii)Na2CO3,CH3CN, reflux;and(iv)Me OH=CH2CI2,H2,Pd=CScheme1Methyl- -D-glucopyranoside-based azacrown ethers52780%obtained with the N -hydroxypropyl lariat ether (3a )decreased to 55%on the ‘‘methylation’’of the hydroxy group (3b )(entries 5and 6).Elimination of the protecting groups led to modest enantioselectiv-ities;the use of free bis-hydroxy derivatives 4a and 4b as the catalyst resulted in ee values of 24and 16%,respectively (entries 7and 8).This can be explained by the notion that without an acetal func-tion the sugar unit has become more flexible and the lipophility was decreased.Presence of the acetal moiety also has a steric impact.Darzens condensationThe glucose-based crown ethers (1–4)induced a moderate asymmetric induction in the condensation of phenacyl chloride (14)with benzaldehyde,which is a well studied model reaction (Scheme 3).The best results were obtained using N -(4-trifluoromethyl-benzyl)cinchoninium bromide (42%ee )[15],or a crown ether incorporating a glucopyranoside unit (62%ee )as a phase transfer catalyst [4].We performed the above reaction in a liquid–liquid (LL)two-phase system.The reagents andtheScheme 2Table 1Enantioselectivities induced by chiral crown ether catalysts 1–4in three reactions of the chalcone (12a )a EntryCat.Michael adduct (13a )Darzens condensation (15a )Epoxidation (15a )Yield =%bee =%(R )Yield =%b ee =%(2R ,3S )Yield =%b ee =%11a 5385c 7462c 5092(2R ,3S )d 21b 4887c 6221c 6123(2R ,3S )d 32a 499075484689(2R ,3S )42b 166854144338(2S ,3R )53a 348061425967(2R ,3S )63b 175552183919(2S ,3R )74a 352476312118(2R ,3S )84b 30166114269(2S ,3R )aThe ee =%was determined by 1H NMR spectroscopy,the absolute configurations were determined by comparing the measured optical rotations with the literature data bBased on isolation by preparative TLC cRef.[4]dRef.[8b]Scheme 3528 A.Mako´et al.catalyst1–4(7mol%)were dissolved in toluene and the reaction was initiated by adding30%sodium hydroxide.After stirring for1–4h at room tempera-ture,the trans-epoxyketone15a was formed in each case in a selective way(de>98%).The predominant enantiomer was the one with negative optical rota-tion that corresponds to an absolute configuration of (2R,3S)[16].Earlier,the best optical yield was achieved in the presence of catalyst1a giving the product(15a)after2h of stirring in an enantioselec-tivity of62%(Table1,entry1)[4].Nearly the same extent of asymmetric induction was detected with the hydroxypropyl naphthyl-methylene and isopropylidene catalysts(2a and3a, respectively).In the former case,the ee was48%, while in the latter case it was42%(entries3and5, respectively).In this series,the lowest value(an ee of31%)was obtained with the unprotected catalyst 4a(entry7).In all cases investigated,‘‘methylation’’of the hydroxypropyl side arm led to lower optical yield;ee values of21,14,18,and14were measured for catalysts1b,2b,3b,and4b,as shown by entries 2,4,6,and8.In these instances,the yields were also significantly lower.A possible explanation is that the increase in the lipophylity is disadvantageous in the toluene-water two-phase system.At the same time, steric and electronic effects are also responsible for the above trends.The quality of the end-group of the bending side arm effects the complexation with the Naþcation that is accompanied by the correspond-ing(Ph C(O)CHCl)Àanion and hence influences the outcome of the Darzens condensation. Asymmetric epoxidation of chalconeSignificant enantioselectivities were generated by the glucose-based crown ethers(1–4)in the epoxi-dation of the chalcone under phase transfer catalytic conditions(Scheme4).The enantioselective epoxi-dation of , -unsaturated ketones employing chiral catalysts has received considerable attention in re-cent years[17].A variety of methods have been de-veloped including the use of polyphasic systems involving hydrogen peroxide in the presence of poly-amino acids[18],alkyl peroxides in conjunction with lanthanoid-binaphthol complexes[19],tartrate-modified metal tert-butyl peroxides[20],and hydro-gen peroxide in the presence of chiral platinium(II) complexes[21].Good enantioselectivities were also reported using non-catalytic systems,like molecular oxygen in the presence of diethylzinc=chiral amino alcohols[22].The use of chiral quaternary ammonium salts as phase-transfer catalyst in the transformation under discussion was also investigated[23].In our experiments,the epoxidation of chalcone (12a)was carried out in a liquid–liquid two-phase system applying tert-butyl hydroperoxide(TBHP,2 equiv.)in toluene,employing20%aq.NaOH(3.5 equiv.)as the base and7mol%of glucopyranoside-based lariat ether1–4at a temperature of0–4 C (Scheme4).Table1summarizes the results obtained in the epoxidation of chalcone in the presence of chiral crown catalysts1–4.It can be seen that the yields and the enantioselectivities are significantly affected by the substituents of the carbohydrate moi-ety.In all experiments the trans-epoxyketone(15) was obtained and in most cases the(2R,3S)isomer of the epoxyketone was formed(with negative opti-cal rotation).Presence of the catalysts having OCH3 end-group2b,3b,and4b generated formation of the (2S,3R)isomer in excess(with positive optical rota-tion).The best ee values(92and89%)were detected in the presence of lariat ethers1a and2a containing an aryl group as protecting moiety in the sugar part. For the isopropylidene derivative3a only an ee of 67%,while for the unprotected lariat ether4a alowScheme4Methyl- -D-glucopyranoside-based azacrown ethers529ee of18%was measured.All these were obtained for the N-hydroxypropyl derivatives1a,2a,and3a. Application of the catalysts with methoxy end-group (1b,2b,3b,and4b)led to decreased ee values(23, 38,19,and9%).The same trend was experienced in the Darzens condensations,but the decrease in ee due to the OH to OCH3change was more significant in the epoxidations.Asymmetric Michael reaction and epoxidationof chalcone analoguesThe Michael addition and epoxidation of a few chal-cone analogues(12b–12e)were investigated in the presence of the best azacrown catalyst2a.The ex-perimental results are listed in Table2.It can be seen that the change of the phenyl ring(in the chalcone) to1-naphthyl,2-naphthyl,and methyl groups re-sulted in a decreased asymmetric induction in the Michael reaction during the formation of adducts 13b–13c and13e.The ee values were35(13b), 43(13c),and64(13e).The highest enantioselectiv-ity was obtained in the case of the pyridyl-chalcone 13d(79%).As the naphthyl groups are sterically de-manding,the decrease in the enantioselectivity may be the consequence of steric effects.It is interesting that the product13c with2-naphthyl substituent was formed with a somewhat higher enantioselectivity (43%)than the13b1-naphthyl derivative(35%). It is noteworthy that while the Michael adducts 13b–13d with aromatic substituents displayed pos-itive specific rotations(suggesting the excess of the same enantiomer configuration in them),the methyl substituted13e was formed with negative specific rotation.The impact of the methyl group in13e on the specific rotation will be clarified at a later stage.Table2summarizes the results obtained in the epoxidation of chalcone analogues in the presence of macrocycle2a.The corresponding trans-epoxy ketones15b–15e were obtained in all cases.The 1-naphthyl15b,2-naphthyl15c,2-pyridyl15d,and methyl-derivative15e were formed with56,64, 45,and51%enantiomeric excesses.It is worth not-ing that a higher enantioselectivity was detected in the case of2-naphthyl compound15c(64%)than with1-napthtyl15b derivative(56%).The com-pounds15c–15e were formed with enantiomeric excesses with negative specific rotations,while the 15b had a positive one.ConclusionsMethyl- -D-glucose based15-crown-5type lariat ethers were protected on C(4)-OH and C(6)-OH via acetal formation using different reagents.The4,6-O-benzylidene(1),4,6-O-(1)-naphthylidene(2),4,6-O-isopropylidene(3)acetals,as well as unprotected lariat ether4were tested as chiral phase transfer cat-alyst in a Michael addition,a Darzens condensation and an epoxidation of the chalcone.The effect of the structural changes on the asymmetric induction was evaluated.The lariat ethers studied differ in polarity and lipophilicity(that is an important point of view in the case of phase transfer catalysts),but the decisive factor is the steric and electronic effect of the substit-uents on the asymmetric induction.In all the three reactions,the best asymmetric induction was achieved by the lariat ethers with4,6-O-Ar moieties containing a hydroxypropyl substituent on the nitrogen atom. It is noteworthy that there was no significant differ-ence between the effect of the benzylidene-and the naphthylidene derivatives(1a and2a,respectively) in the Michael addition and in the epoxidation ofTable2Asymmetric Michael addition and epoxidation of chalcone analogues(12b–12e)mediated by chiral azacrown ether2a Michael addition EpoxidationAdduct Yield=%a½ D= gÀ1cm3dmÀ1b ee=%c Product Yield=%a½ D= gÀ1cm3dmÀ1b ee=%c 13b47þ92.13515b51þ63.05613c12þ68.84315c15À153.26413d81þ118.27915d58À113.74513e65À23.56415e42À3.251a Based on isolation by preparative TLCb In CH2Cl2at20 Cc Determined by1H NMR spectroscopy530 A.Mako´et al.chalcone.In the Michael addition,enantioselectivities of85(1a)and90%(2a),while in the epoxidation, ee values of92(1a)and89%(2a)were detected.In the Darzens condensation,the presence of the ste-rically demanding naphthyl group caused a signifi-cant decrease in the ee value:62(1a)vs.48%(2a). The use of catalysts with the smaller isopropyli-dene protecting group led to more modest results. Applying3a,ee values of80,42,and67%were measured in the Michael addition,Darzens con-densation and epoxidation,respectively.The lowest enantioselectivities was experienced in the case of macrocycles without any protecting groups(4a–4b). This may be caused on one hand by the lack of a sterically demanding protecting group while,on the other hand,by the moreflexible hetero ring.Flexible ligands can match both guest enantiomers by adjust-ing its conformation,and therefore,provide little or no enantiomer recognition.It is noteworthy that the use of lariat ethers with methoxypropyl N-substituent(2b,3b,and4b)in epoxidation reactions resulted in an enantiomeric ex-cess,where the(2S,3R)antipode was predominant. The application of the hydroxypropyl-macrocycles (1a,2a,3a,and4a)induced the preferred formation of the(2R,3S)enantiomer.Lower enantioselectivities were obtained in the reactions of the chalcone analogues in the presence of catalyst2a than in the case of the proper chalcone. ExperimentalMelting points were taken on using a Bu¨chi510apparatus (compounds crystallized from ethanol).The specific rotation was measured with the help of a Perkin-Elmer241polarimeter at22 C.NMR spectra were obtained on a Bruker300and a Bruker DRX-500instrument in CDC13with TMS as the internal standard.Mass spectra were registrated from m-nitro-benzyl alcohol(NOBA)matrix on a Varian MA T312instru-ment.Analytical and preparative thin layer chromatography was performed on silica gel plates(60GF-254,Merck),while column chromatography was carried out using70–230mesh silica gel(Merck).Chemicals and the shift reagent Eu(hfc)3 were purchased from Aldrich Chem.Co.1-Naphtaldehyde dimethyl acetal(5,C13H14O2)A mixture of57.3g1-naphthaldehyde(366mmol),63.8g freshly distilled trimethyl orthoformate(602mmol),153cm3 dry methanol and0.37g zinc chloride(3mmol)was refluxed for6h under dry conditions.Part of the solvent(about70cm3) was removed in vacuo and an additional portion18.4g of trimethyl orthoformate(173mmol)was added.The reaction mixture was heated at reflux for overnight and was monitored by TLC.The excess of trimethyl orthoformate and the solvent was removed under reduced pressure,the residue was treated with200cm35%aqueous NaHCO3and extracted with diethyl ether(3Â100cm3).The combined ether extract was washed with water(100cm3),dried(MgSO4)and concentrated to give intermediate5as brown syrup.Yield70.4g(95%);1H NMR (300MHz,CDCl3): ¼8.27(d,J¼8.2Hz,1H,Ar H),7.81 (d,J¼7.5Hz,1H,Ar H),7.79(d,J¼8.2Hz,1H,Ar H),7.71 (d,J¼7Hz,1H,Ar H),7.40–7.52(m,3H,Ar H),5.89(s,1H, CH),3.34(s,6H,OCH3)ppm;13C NMR(75MHz,CDCl3): ¼133.94,133.18,130.92,129.34,128.61,126.28,125.75, 125.08,124.90,124.33(Ar C),102.40(CH),53.15(2OCH3) ppm;FAB-MS:m=z¼202[M]þ;HRMS:m=z calcd for C13H14O2[M]þ202.0994,found202.0997.Methyl4,6-O-(1-naphthyl)methylene- -D-glucopyranoside (6,C18H20O6)To a solution of20.0g methyl- -D-glucopyranoside (103mmol),26.0g of1-naphthaldehyde dimethyl acetal (128mmol)in150cm3of dry DMF4.5g of10-camphor-sulfonic acid(19.4mmol)was added in parts so the pH of mixture be2–3.The reaction mixture was stirred at room temperature for12h,and then the methanol formed was re-moved by evaporating in vacuo.An additional10.8g1-naphthaldehyde dimethyl acetal(53mmol)was added.After 12h reflux the mixture was concentrated in vacuo.The residue was taken up in dichloromethane(500cm3)and neutralized with solution of NaHCO3(so the pH of the mixture be8), washed with water(3Â200cm3).The organic phase was dried (Na2SO4).The crude product obtained in evaporation was purified by crystallization(from Et OH:hexane,6:1).Yield 20.5g(60%);½D20¼þ122.4 gÀ1cm3dmÀ1(c¼0.5, CHCl3);mp221–223 C;1H NMR(500MHz,CDCl3): ¼8.19(d,J¼8.5Hz,1H,Ar H),7.86(d,J¼8.2Hz,2H, Ar H),7.75(d,J¼7.1Hz,1H,Ar H),7.54(t,J¼7.3Hz,1H, Ar H),7.45–7.50(m,2H,Ar H),6.09(s,1H,napht-CH), 4.84(d,J¼3.9Hz,1H,H-1),4.40(dd,J¼4.5,9.9Hz, 1H,H-6),3.98(t,J¼9.3Hz,1H,H-4),3.93(dd,J¼4.3, 9.3Hz,1H,H-6)3.88(t,J¼10.3Hz,1H,H-3),3.67–3.71 (m,1H,H-5),3.64(t,J¼9.3Hz,1H,H-2),3.50(s,3H, OCH3)ppm;13C NMR(75MHz,CDCl3): ¼133.86, 132.18,130.41,129.93,128.63,126.38,125.72,124.98, 124.64,124.03(Ar C),101.29(napht-CH),99.83(C-1), 81.37(C-4),72.90(C-2),71.86(C-3),69.27(C-6),62.43 (C-5),55.69(OCH3)ppm;FAB-MS:m=z¼333[Mþ1]þ, 355[MþNa]þ;HRMS:m=z calcd for C18H20O6[M]þ332.1260,found332.1253.General method for the preparation of compounds7,10A solution of6or9(43.8mmol)and12.5g tetrabutylammo-nium hydrogensulfate(36.9mmol)in93cm3bis(2-chloro-ethyl)ether(650.3mmol)was vigorously stirred with93cm3 50%NaOH solution at room temperature for18h.To the reaction mixture were added160cm3CH2Cl2and160cm3 water.The organic layer was decanted and the aqueous phase was washed with CH2Cl2(3Â60cm3).The combined organic phases were washed with water and dried(MgSO4).Methyl- -D-glucopyranoside-based azacrown ethers531After removal of the solvent and the excess of the bis(2-chloroethyl)ether,the product was purified by column chro-matography (silica gel,CH 2Cl 2–Me OH (100:1!100:7)as the eluant),to give products 7and 10.Methyl 4,6-O-(1-naphthyl)methylene-2,3-bis[(2-chloro-ethoxy)ethyl]- -D -glucopyranoside (7,C 26H 34Cl 2O 8)Yield 12.6g (53%);½ D 20¼þ73.7 g À1cm 3dm À1(c ¼1,CHCl 3);mp 132 C;1H NMR (500MHz,CDCl 3): ¼8.16(d,J ¼8.3Hz,1H,Ar H),7.86(d,J ¼8.1Hz,2H,Ar H),7.77(d,J ¼7.1Hz,1H,Ar H),7.52(t,J ¼7.2Hz,1H,Ar H),7.45–7.50(m,2H,Ar H),6.07(s,1H,napht-CH),4.90(d,J ¼3.6Hz,1H,H-1),4.38(dd,J ¼4.5,9.9Hz,1H,H-6),3.95–3.98(m,1H,H-5),3.92(dd,J ¼4.4,9.5Hz,1H,H-6)3.84–3.88(m,4H,4podand arm-H),3.82(t,J ¼9.2Hz,1H,H-3),3.77(t,2H,J ¼5.8Hz,2podand arm-H),3.67–3.73(m,3H,H-4,2podand arm-H),3.64(t,J ¼5.9Hz,2H,2podand arm-H),3.52–3.59(m,5H,H-2,CH 2Cl,2podand arm-H),3.48(s,3H,OCH 3),3.39(t,J ¼5.9Hz,2H,CH 2Cl)ppm;13C NMR (125MHz,CDCl 3): ¼133.73,132.51,130.47,129.70,128.56,126.15,125.66,124.99,124.16,123.99(Ar C),100.56(napht-CH),99.22(C-1),82.26(C-4),80.69(C-2),79.12(C-3),72.19,71.54,71.32,71.05,70.93,70.63(6OCH 2of the podand arm),69.40(C-6),62.37(C-5),55.41(OCH 3),42.88,42.64(2CH 2Cl)ppm;FAB-MS:m =z ¼545[M þ1]þ,547[M þ1]þ,567[M þNa]þ569[M þNa]þ;HRMS:m =z calcd for C 26H 34Cl 2O 8[M]þ544.1631,found 544.1622.Methyl 4,6-O-isopropylidene-2,3-bis[(2-chloroethoxy)ethyl]- -D -glucopyranoside (10,C 18H 32Cl 2O 8)Yield 11.6(59%);½ D 20¼þ59.4 g À1cm 3dm À1(c ¼1,CHCl 3);1H NMR (500MHz,CDCl 3): ¼4.75(d,J ¼3.6Hz,1H,H-1),4.01(dd,J ¼4.7,10.3Hz,1H,H-6),3.82–3.87(m,2H,2podand arm-H),3.74–3.80(m,3H,H-3,2podand arm-H),3.68(t,J ¼6.2Hz,4H,4podand arm-H),3.47–3.64(m,11H,H-4,H-5,H-6,2CH 2Cl,4podand arm-H),3.38(dd,J ¼3.3,8.9Hz,1H,H-2),3.34(s,3H,OCH 3),1.42(s,3H,CH 3),1.34(s,3H,CH 3)ppm;FAB-MS:m =z ¼447,449[M þ1]þ,469,471[M þNa]þ;HRMS:m =z calcd for C 18H 32Cl 2O 8[M]þ446.1474,found 446.1479.General method for the preparation of compounds 8,11A mixture of bis-chloro derivative 7or 10(36.4mmol)and NaI (21.8g,145.3mmol)in dry acetone (360cm 3)was stirred under reflux for 22h.After cooling,the precipitate was filtered and washed with acetone.The combined ace-tone solutions were evaporated in vacuum.The residue was dissolved in CH 2Cl 2(200cm 3),washed with water and dried (Na 2SO 4).Evaporation of the solvent afforded the products 8and 11as yellow oils,which were used without further purification.Methyl 4,6-O-(1-naphthyl)methylene-2,3-bis[(2-iodoethoxy)-ethyl]- -D -glucopyranoside (8,C 26H 34I 2O 8)Yield 24.9(94%);½ D 20¼þ50.0 g À1cm 3dm À1(c ¼1,CHCl 3);mp 81–82 C;1H NMR (500MHz,CDCl 3): ¼8.16(d,J ¼8.3Hz,1H,Ar H),7.85(d,J ¼7.9Hz,2H,Ar H),7.77(d,J ¼7.0Hz,1H,napht-H),7.45–7.54(m,3H,Ar H),6.07(s,1H,napht-CH), 4.91(d,J ¼3.7Hz,1H,H-1), 4.37(dd,J ¼4.5,9.9Hz,1H,H-6),3.95–3.98(m,1H,H-5),3.92(d,J ¼4.4,9.5Hz,1H,H-6),3.84–3.88(m,4H,4podand arm-H),3.82(t,J ¼9.2Hz,1H,H-3),3.77(t,J ¼6.8Hz,2H,2podand arm-H),3.64–3.72(m,3H,H-4,2podand arm-H),3.50–3.58(m,5H,H-2,4podand arm-H),3.48(s,3H,OCH 3),3.27(t,J ¼6.8Hz,2H,CH 2I),3.03(t,J ¼6.9Hz,2H,CH 2I)ppm;13C NMR (125MHz,CDCl 3): ¼133.72,132.50,130.46,129.70,128.57,126.14,125.64,124.99,124.14,123.96(Ar C),100.51(napht-CH),99.22(C-1),82.22(C-4),80.59(C-2),79.14(C-3),72.22,71.86,71.60,71.53,70.63,70.23(6OCH 2of the podand arm),69.37(C-6),62.36(C-5),55.41(OCH 3),3.02,2.95(2CH 2I)ppm;FAB-MS:m =z ¼729[M þ1]þ,751[M þNa]þ;HRMS:m =z calcd for C 26H 34I 2O 8[M]þ728.0343,found 728.0356.Methyl 4,6-O-isopropylidene-2,3-bis[(2-iodoethoxy)ethyl]- -D -glucopyranoside (11,C 18H 32I 2O 8)Yield 21.1(92%);½ D 20¼þ75.0 g À1cm 3dm À1(c ¼1,CHCl 3);1H NMR (500MHz,CDCl 3): ¼4.81(d,J ¼3.6Hz,1H,H-1),4.07(dd,J ¼4.8,10.1Hz,1H,H-6),3.88–3.93(m,2H,2podand arm-H),3.79–3.85(m,3H,H-3,2podand arm-H),3.74(t,J ¼7.2Hz,4H,4podand arm-H),3.55–3.70(m,7H,H-4,H-5,H-6,4podand arm-H),3.43(dd,J ¼3.5,9.0Hz,1H,H-2),3.40(s,3H,OCH 3),3.22–3.28(m,4H,2CH 2I),1.48(s,3H,CH 3),1.40(s,3H,CH 3)ppm;FAB-MS:m =z ¼631[M þ1]þ,653[M þNa]þ;HRMS:m =z calcd for C 18H 32I 2O 8[M]þ630.0187,found 630.0181.General method for the preparation of crown ethers 2,3A mixture of 3.84g anhydrous Na 2CO 3(36.2mmol),the cor-responding primary amine (4.60mmol)and bis-iodo 8or 11(4.60mmol)in 100cm 3dry acetonitrile was stirred and refluxed for 24–48h,under argon.After cooling,the precipi-tate was filtered and washed with acetonitrile.The combined organic solutions were concentrated in vacuo .The residual oil was dissolved in CHCl 3,washed with water and dried (Na 2SO 4),and the solvent was evaporated.The crude mono-aza-crown ether (2or 3)was purified by column chromato-graphy on silica gel using CHCl 3:Me OH (100:2!100:7)as the eluant.Methyl 4,6-O-(1-naphthyl)methylene-2,3-dideoxy- -D -gluco-pyranosido(2,3-h)-N-hydroxypropyl-1,4,7,10-tetraoxa-l3-azacyclopentadecane (2a ,C 29H 41NO 9)Yield 1.2g (47%);½ D 20¼þ77.4 g À1cm 3dm À1(c ¼0.5,CHCl 3);mp 98–100 C;1H NMR (500MHz,CDCl 3): ¼8.13(d,J ¼8.1Hz,1H,Ar H),7.85(d,J ¼7.8Hz,2H,Ar H),7.77(d,J ¼7.0Hz,1H,Ar H),7.45–7.52(m,3H,Ar H),6.07(s,1H,napht-CH),4.87(d,J ¼3.4Hz,1H,H-1),4.38(dd,J ¼4.4,9.8Hz,1H,H-6),3.88–3.93(m,2H,H-5,H-6),3.86(m,2H,OCH 2of the macrocycle),3.77–3.81(m,4H,2OCH 2of the macrocycle), 3.73(t,J ¼9.2Hz,1H,H-3), 3.62–3.69(m,5H,H-4and 2OCH 2of the macrocycle),3.60(t,J ¼5.2Hz,2H,OCH 2of the macrocycle),3.54(dd,J ¼3.1,8.1Hz,1H,H-2),3.46(s,3H,OCH 3),3.42–3.48(m,2H,NCH 2CH 2C H 2),2.65–2.87(m,6H,3NCH 2),1.60–1.72(m,532A.Mako´et al.2H,NCH 2C H 2CH 2)ppm;13C NMR (75MHz,CDCl 3): ¼133.71,132.52,130.50,129.61,128.52,126.06,125.63,125.00,124.13,123.69(Ar C),100.21(napht-CH),98.58(C-1),82.85(C-4),79.87(C-2),77.90(C-3),72.33,70.67,70.37,69.37,69.11,68.91(6OCH 2of the macrocycle),69.78(C-6),64.23(NCH 2CH 2C H 2),62.25(C-5),56.76(N C H 2CH 2CH 2),55.27(OCH 3),54.68,54.37(2NCH 2of the macrocycle),28.41(NCH 2C H 2CH 2)ppm;FAB-MS:m =z ¼548[M þH]þ,570[M þNa]þ;HRMS:m =z calcd for C 29H 41NO 9[M]þ547.2781,found 547.2792.Methyl 4,6-O-(1-naphthyl)methylene-2,3-dideoxy- -D -gluco-pyranosido(2,3-h)-N-methoxypropyl-1,4,7,10-tetraoxa-l3-azacyclopentadecane (2b ,C 30H 43NO 9)Yield 1.13g (44%);½ D 20¼þ80.3 g À1cm 3dm À1(c ¼1,CHCl 3);mp 106–108 C;1H NMR (500MHz,CDCl 3): ¼8.13(d,J ¼8.1Hz,1H,Ar H),7.84(d,J ¼7.9Hz,2H,Ar H),7.78(d,J ¼7.1Hz,1H,Ar H),7.45–7.52(m,3H,Ar H),6.06(s,1H,napht-CH),4.88(d,J ¼3.6Hz,1H,H-1),4.38(dd,J ¼4.4,9.7Hz,1H,H-6),3.89–3.95(m,2H,H-5,H-6),3.83–3.87(m,2H,OCH 2of the macrocycle),3.75–3.81(m,4H,2OCH 2of the macrocycle),3.73(t,J ¼9.2Hz,1H,H-3),3.63–3.69(m,3H,H-4,OCH 2of the macrocycle),3.57–3.61(m,2H,OCH 2of the macrocycle),3.50–3.55(m,3H,H-2,OCH 2of the macrocycle),3.46(s,3H,OCH 3),3.40(t,J ¼6.3Hz,2H,NCH 2CH 2C H 2),3.31(s,3H,CH 2OC H 3),2.56–2.85(m,6H,3NCH 2),1.68–1.74(m,2H,NCH 2C H 2CH 2)ppm;13C NMR (75MHz,CDCl 3): ¼133.70,132.49,130.50,129.61,128.52,126.05,125.63,124.99,124.14,123.65(Ar C),100.21(napht-CH),98.53(C-1),82.81(C-4),79.96(C-2),77.94(C-3),72.28,70.73,70.33,69.85,69.37,69.30(OCH 2of the macrocycle),70.93(NCH 2CH 2C H 2),69.94(C-6),62.27(C-5),58.54(CH 2O C H 3),55.30(OCH 3),54.53(2NCH 2of the macrocycle),53.53(N C H 2CH 2CH 2),27.63(NCH 2C H 2CH 2)ppm;FAB-MS:m =z ¼562[M þH]þ,584[M þNa]þ;HRMS:m =z calcd for C 30H 43NO 9[M]þ561.2938,found 561.2943.Methyl 4,6-O-isopropylidene-2,3-dideoxy- -D -glucopyrano-sido(2,3-h)-N-hydroxypropyl-1,4,7,10-tetraoxa-l3-aza-cyclopentadecane (3a ,C 21H 39NO 9)Yield:0.83g (40%);½ D 20¼þ77.0 g À1cm 3dm À1(c ¼1,CHCl 3);1H NMR (500MHz,CDCl 3): ¼4.79(d,J ¼3.6Hz,1H,H-1),4.08(dd,J ¼4.8,10.1Hz,1H,H-6),3.83–3.90(m,2H,OCH 2of the macrocycle),3.78–3.81(m,2H,OCH 2of the macrocycle),3.68–3.76(m,3H,H-3,OCH 2of the macro-cycle),3.54–3.67(m,10H,H-2,H-4,H-5,H-6,3OCH 2of the macrocycle),3.41–3.43(m,2H,NCH 2CH 2C H 2),3.39(s,3H,OCH 3),2.70–2.83(m,6H,3NCH 2),1.65–1.69(m,2H,NCH 2C H 2CH 2),1.48(s,3H,CH 3),1.39(s,3H,CH 3)ppm;13C NMR (75MHz,CDCl 3): ¼99.24[C (CH 3)2],98.27(C-1),79.65(C-2),78.19(C-3),74.72(C-4),72.07,70.36,70.29,69.76,68.48,68.40(6OCH 2of the macrocycle),63.42(NCH 2CH 2C H 2),63.02(C-6),62.48(C-5),56.43(N C H 2CH 2CH 2),55.00(OCH 3),54.53,54.30(2NCH 2of the macrocycle),29.58,29.11(2CH 3),28.04(NCH 2C H 2CH 2)ppm;FAB-MS:m =z ¼450[M þH]þ,472[M þNa]þ;HRMS:m =z calcd for C 21H 39NO 9[M]þ449.2625,found 449.2633.Methyl 4,6-O-isopropylidene-2,3-dideoxy- -D -glucopyrano-sido(2,3-h)-N-methoxypropyl-1,4,7,10-tetraoxa-l3-aza-cyclopentadecane (3b ,C 22H 41NO 9)Yield 0.88g (42%);½ D 20¼þ87.0 g À1cm 3dm À1(c ¼1,CHCl 3);1H NMR (500MHz,CDCl 3): ¼4.81(d,J ¼3.6Hz,1H,H-1),4.08(dd,J ¼4.8,10.1Hz,1H,H-6),3.51–3.95(m,17H,H-2,H-3,H-4,H-5,H-6,6OCH 2of the macrocycle),3.42–3.43(m,2H,NCH 2CH 2C H 2),3.41(s,3H,OCH 3),3.32(s,3H,CH 2OC H 3),2.58–2.86(m,6H,3NCH 2),1.70–1.76(m,2H,NCH 2C H 2CH 2),1.48(s,3H,CH 3),1.40(s,3H,CH 3)ppm;13C NMR (75MHz,CDCl 3): ¼99.28[C (CH 3)2],98.27(C-1),79.88(C-2),78.25(C-3),74.77(C-4),72.15,70.43,69.93,69.27,69.25,68.87(6OCH 2of the macrocycle),70.79(NCH 2CH 2C H 2),63.06(C-6),62.54(C-5),58.53(CH 2O C H 3),55.04(OCH 3),54.46,54.43(2NCH 2of the macrocycle),53.52(N C H 2CH 2CH 2),29.62(CH 3),29.16(NCH 2C H 2CH 2),27.24(CH 3)ppm;FAB-MS:m =z ¼464[M þH]þ,486[M þNa]þ;HRMS:m =z calcd for C 22H 41NO 9[M]þ4463.2781,found 463.2790.General procedure for the preparation of compounds 4a ,4b Compound 1a or 1b (4.82mmol)and 1:1mixture of Me OH–CH 2Cl 2(25cm 3)were placed into a hydrogenation bottle,Pd =C (10%,120mg)was added,the air was replaced by argon and then the argon by hydrogen and the mixture was shaken under H 2for 6h at ambient temperature.The mixture was filtered through a Celite pad and the volatile components were removed under reduced pressure to fur-nish as a syrup 4a or 4b ,which were used without further purification.Methyl-2,3-dideoxy- -D -glucopyranosido(2,3-h)-N-hydroxy-propyl-1,4,7,10-tetraoxa-l3-azacyclopentadecane (4a ,C 18H 35NO 9)Yield 1.77g (90%);½ D 20¼þ81.0 g À1cm 3dm À1(c ¼1,CHCl 3);1H NMR (500MHz,CDCl 3): ¼5.10(d,J ¼3.6Hz,1H,H-1),3.47–4.07(m,20H,NCH 2CH 2C H 2,H-2,H-3,H-4,H-5,2H-6,6OCH 2of the macrocycle),3.43(s,3H,OCH 3),2.45–2.81(m,6H,3NCH 2),1.60–1.68(m,2H,NCH 2C H 2CH 2)ppm;13C NMR (75MHz,CDCl 3): ¼96.68(C-1),80.41(C-2),79.20(C-3),71.97(C-4),71.34,70.96,70.50,70.05,69.18,69.10(6OCH 2of the macrocycle),67.02(C-5),64.46(CH 2OH),62.06(C-6),55.06(OCH 3),54.78(2NCH 2of the macrocycle),54.19(N C H 2CH 2CH 2),29.14(NCH 2C H 2CH 2)ppm;FAB-MS:m =z ¼410[M þH]þ,432[M þNa]þ;HRMS:m =z calcd for C 18H 35NO 9[M]þ409.2312,found 409.2325.Methyl-2,3-dideoxy- -D -glucopyranosido(2,3-h)-N-methoxy-propyl-1,4,7,10-tetraoxa-l3-azacyclopentadecane (4b ,C 19H 37NO 9)Yield 1.87g (92%);½ D 20¼þ78.5 g À1cm 3dm À1(c ¼1,CHCl 3);1H NMR (500MHz,CDCl 3): ¼5.09(d,J ¼3.6Hz,1H,H-1),3.51–4.08(m,18H,H-2,H-3,H-4,H-5,2H-6and 6OCH 2of the macrocycle),3.42(t,J ¼6.0Hz,2H,NCH 2-CH 2C H 2),3.43(s,3H,OCH 3),3.32(s,3H,CH 2OC H 3),2.63–2.84(m,4H,2NCH 2of the macrocycle),2.57(t,J ¼7.1Hz,2H,NC H 2CH 2CH 2),1.72(m,2H,NCH 2C H 2CH 2)ppm;13CMethyl- -D -glucopyranoside-based azacrown ethers 533。
