Phosphorylation of D-glucose derivatives with inorganic cyclo-triphosphate: substituent effect at the 5-CH2OH or 2-OH group

The phosphorylation of several D-glucose derivatives has been achieved using inorganic sodium cyclo-triphosphate hexahydrate (P3m), Na3P3O9 x 6H2O, in aqueous solution. In the phosphorylation of D-glucuronic acid, 6-phosphoryl-D-glucose and D-xylose, beta-D-glucuronic acid 1-triphosphate, 6-phosphoryl-beta-D-glucose 1-triphosphate and beta-D-xylose 1-triphosphate were synthesized stereoselectively with maximum yields of 43.5, 32.8 and 41.9%, respectively. In the case of D-glucosamine and 2-deoxy-D-glucose, the main phosphorylated products were assigned to beta-D-glucosamine 1-triphosphate and 2-deoxy-beta-D-glucose 1-triphosphate by 1H-, 13C- and 31P-NMR, and the yields were 13.9 and 13.4%, respectively.     

几种齐墩果酸糖缀合物的合成

报道了齐墩果酸与四种单糖和二糖（葡萄糖、半乳糖、乳糖及葡萄糖醛酸）进 行糖苷化制备糖缀合物的方法。在合成过程中首先将葡萄糖、半乳糖及乳糖转化成 相应的全苯甲酰三氯亚胺酯糖基供体（10a-10c），将葡萄糖醛酸转化成为1-溴代 乙酰葡萄糖醛酸甲酯糖基供体（10d）；在齐墩果酸的28-位羧基上进行酰胺化引入 ω-氨基羧酸甲酯得到其衍生物6。然后10a-10c在TMSOTf的催化下与化合物6的3-位 羟基进行β-糖苷化；10d在AgOTf的催化下与6进行β-糖苷化，最后脱掉保护基得 到相应的糖缀合物13a-13d，所有目的化合物均为新化合物，其结构经IR，^1H NMR，^13C NMR，2D-COSY，HMQC，DEPT及HRMS进行了确证。     

Reactions of methyl (E,Z)-2-(2-benzoyl-2-ethoxycarbonyl-1-ethenyl)-amino-3-dimethylaminopropenoate with heteroarylhydrazines. 2-(2-Benzoyl-2-ethoxycarbonyl-1-ethenyl)amino-3-heteroarylhydra-zonopropanoates and 1-heteroaryl-4-ethoxycarbonyl-3-phenylpyrazoles

In the reaction of methyl (E,Z)-2-(2-benzoyl-2-ethoxycarbonyl-1-ethenyl)amino-3-dimethylaminopro-penoate ( 1 ) with heteroarylhydrazines 2 in ethanol in the presence of catalytic amounts of hydrochloric acid two types of products were formed: methyl 2-(2-benzoyl-2-ethoxycarbonyl-1-ethenyl)amino-3-heteroaryl-hydrazonopropanoates 4 in 73-86% yield and 1-heteroaryl-4-ethoxycarbony-3-phenylpyrazoles 5 in 5-16% yield.     

Reaction of Pyrimidinonethione Derivatives: Synthesis of N‐Methyl‐2‐Hydrizinopyrimidine‐4‐One,Thiazolo[3,4‐b] N‐Methylpyrimidinone; 2‐(1‐Pyrazolonyl) N‐Methylpyrimidine‐4‐one and 2‐Hydrazino‐N‐Methyl Pyrimidine‐4‐One Derivatives

6‐Aryl‐5‐cyano‐4‐pyrimidinone‐2‐thion derivatives 1a‐c reacted with methyl iodide (1:2) to give the corresponding 2‐S,N‐dimethyl pyrimidine‐4‐one derivatives 2a‐c . Compounds 2a‐c were in turn, reacted with hydrazine hydrate to give the sulfur free reaction products 3a‐c . These reaction products were taken as the starting materials for the synthesis of several new heterocyclic derivatives. Reaction of 3a‐c with acetic anhydride and formic acid gave pyrimido triazines 4a‐c and 7a‐c , respectively. Their reactions with active methylene containing reagents gave the corresponding 2‐(1‐pyrazonyl)‐N‐methyl pyrimidine derivatives 9a‐c and 10a‐c , respectively. Their reactions with aromatic aldehydes afforded the corresponding 2‐hydrazono pyrimidine derivatives 11a‐c . The structure of these reactions products were established based on both elemental analysis and spectral data studies.     

New insights into the acid-promoted reaction of caffeic acid and its esters with nitrite: decarboxylation drives chain nitrosation pathways toward novel oxime derivatives and oxidation/fragmentation products thereof

In 0.05 M acetate buffer, pH 4, containing 1% methanol, caffeic acid (1a) (2 x 10(-3) M) reacted smoothly with nitrite (NO(2)(-)) (4 x 10(-3) M) to afford as main products the novel 2-hydroxy- and 2-methoxyaldoximes 7a,b, the 2-oxoaldoxime 9a, 3,4-dihydroxybenzoic acid, 3,4-dihydroxybenzaldehyde, and the known furoxan 3c and benzoxazinone 4b in smaller amounts. At lower 1a concentration (e.g., 1 x 10(-4) M), 7a was the main product, whereas with 0.1 M 1a and 0.5 M NO(2)(-) 3c and 9a were prevailing. At pH 2, 7a was still the most abundant product, together with 3,4-dihydroxybenzaldehyde and some 9a, whereas at pH 1 9a and 3,4-dihydroxybenzaldehyde were formed in higher yields. No evidence for ring nitration products, including the previously reported 4,5-dihydroxy-2-nitrobenzaldehyde, was obtained. At 2 x 10(-3) M concentration and at pH 4, caffeic acid methyl ester (1b) reacted with NO(2)(-) chiefly via ring nitration and/or dimerization to give 5a, the novel nitrated neolignan derivative 10, and the parent 6. Chlorogenic acid (1c) afforded only the ring nitrated derivative 5b. A unifying mechanism for the reaction of 1a and its esters with NO(2)(-) is proposed involving reversible formation of nitroso intermediates via chain nitrosation at the 2-position of the (E)-3-(3,4-dihydroxyphenyl)propenoic system. In the case of 1a, decarboxylation would drive the nitroso intermediates toward the formation of oximes 7a,b and 3c, reflecting nucleophilic addition of water, methanol, and NO(2)(-), and their oxidation or breakdown products, viz. 9a, 3,4-dihydroxybenzaldehyde, 3,4-dihydroxybenzoic acid, and the benzoxazinone 4b. In the case of esters 1b,c, to which decarboxylation is precluded, ring nitration or dimerization become the favored routes, triggered by preliminary oxidation at the catechol moiety.     

Fluorinations with complex metal fluorides. Part 7. Fluorinations of the methyl pyridines with caesium tetrafluorocobaltate

4-Methylpyridine passed over caesium tetrafluorocobaltate at 330 – 340° gave tridecafluoro(1,3-dimethylpyrrolidine) (1) and its 3-difluoromethyl analogue (2), together with a range of polyfluoro-4-picolines (4 – 10) with ?CF₃, ?CHF₂ or ?CH₂F groups in the 4-position. 3-Methylpyridine similarly gave 1 and its 1,2-isomer (11) together with several polyfluoro-3-picolines (14 – 18). 2-Methylpyridine at 270° gave tridecafluoro(1-ethylpyrrolidine) (13), a trace of 11 and 2-trifluoromethyl- (22), 2-difluoromethyl- (23) and 2-fluoromethyl-tetrafluoropyridine (24); there were also products arising by loss of methyl. Other unidentified fluoroalkylpyridines besides those isolated were present in each case.     

Factors affecting the selectivity of the oxidation of methyl p-toluate by cobalt(III)

The anaerobic oxidation of methyl p-toluate by cobalt(III) in acetic acid was investigated. Observed products were 4-carbomethoxybenzaldehyde (2), 4-carbomethoxybenzoic acid (3), 4-carbomethoxybenzyl acetate (1), 4,4'-dicarbomethoxybibenzyl (6), methyl 2,4-dimethylbenzoate (8), and methyl 3,4-dimethylbenzoate (9). Deuterium isotope labeling showed that 2 was not formed from 1, but appeared to be formed directly from methyl p-toluate via 4-carbomethoxybenzyl alcohol (5). The ratio of (2 + 3) to 1 was 0.5 with [py3Co3O(OAc)5OH[PF6] and 1.0 with cobaltic acetate. Cobaltic acetate was generated in situ by the reaction of cobaltous acetate and peracetic acid. When the oxidation was carried out in the presence of chromium (0.05 equiv based on cobalt), the ratio increased dramatically and no 6 was observed. Other transition metals such as vanadium, molybdenum, and manganese had a similar effect, but were not as effective as chromium. Chromium was observed to form a mixed-metal cluster complex with cobalt. Treatment of an acetic acid solution of cobaltous acetate and methyl isonicotinate with K2CrO4 produced a solid tentatively identified as [(MIN)3Co2CrO(OAc)6][CrO4H] (MIN = methyl isonicotinate). The selectivity for the oxidation of methyl p-toluate exhibited by the mixed-metal cluster complex was similar to that observed by the addition of chromium to oxidations using [py3Co3O(OAc)5OH[PF6].     

新型齐墩果酸糖苷化衍生物的合成及体外抗HCT8活性

为提高齐墩果酸的水溶性和稳定性,以齐墩果酸苷元为起始原料,对其28-COOH进行甲基化修饰后制得齐墩果酸-28-羧甲酯(1)。分别以D-半乳糖、D-葡萄糖、D-氨基葡萄糖为起始原料,通过对糖羟基的保护与去保护,得到一系列的二糖、四糖片段。通过三氯乙酰亚胺酸酯途径和对甲苯硫基途径,利用合成的糖片段对1的3-位羟基进行糖化学结构修饰,合成了4种新型的齐墩果酸糖苷化衍生物(2~5),其结构经1H NMR,13C NMR和MS(ESI)表征。采用MTT法测试了2~5对高表达人结肠癌细胞(HCT8)的体外抑制活性。结果表明:2~5对HCT8有一定的抑制作用,化合物5浓度为1×10^-3 mmol/L时,抑制率达到(98.96±0.10)%。     

Stereospecific substitution of enantiomerically pure 1-(2-pyridinyl)ethyl methanesulfonate with beta-dicarbony compounds

The alkylation of the sodium salt of the malonic acid diester with (R)-1-(2-pyridinyl)ethyl methanesulfonate (2) gave the dimethyl (R)-[1-(2-pyridinyl)ethyl]malonate (3a), stereospecifically. The alkylation reaction of methyl acetoacetate gave the methyl (2'S,2R/2S)-3-oxo-2-[1-(2-pyridinyl)ethyl]butanoate (3d) along with the methyl (S)-3-[1-(2-pyridinyl)ethoxy]-2-butenoate (4d). The acid hydrolysis and decarboxylation of 3d under acidic conditions gave (R)-4-(2-pyridinyl)pentan-2-one (6), and the alkylation of methyl (R)-[1-(2-pyridinyl)ethyl]acetoacetate with benzyl bromide gave a mixture of C-benzylated and O-benzylated products 7 and 8.     

Phosphorylation of disaccharides with inorganic cyclo-triphosphate in aqueous solution

The phosphorylation of disaccharides by inorganic cyclo-triphosphate (P(3m)) with a six-membered ring was examined in aqueous solution. In the phosphorylation of cellobiose, lactose, and alpha,alpha-trehalose with P(3m), beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranosyl 1-triphosphate, beta-D-galactopyranosyl-(1-->4)-beta-D-glucopyranosyl 1-triphosphate, and 3-O-triphospho-alpha-D-glucopyranosyl-(1-->1)-alpha-D-glucopyranoside were synthesized with maximum yields of 28%, 35%, and 20%, respectively. In the reactions of maltose and sucrose with P(3m), two phosphorylated products were obtained in yields of 42% and 58%, respectively. The main phosphorylated products were assigned to alpha-D-glucopyranosyl-(1-->4)-beta-D-glucopyranosyl 1-triphosphate and beta-D-fructofuranosyl-(2-->1)-2-O-triphospho-alpha-D-glucopyranoside by heteronuclear multiple bond correlation (HMBC) NMR. The phosphorylation mechanism of disaccharides with P(3m) is discussed.     

茯苓菌丝体多糖的分离及结构分析

由茯苓菌种在培养基中于 2 5℃下培养一周得茯苓菌丝体 .分别用 0 9%NaCl水溶液、热水、0 5mol/LNaOH和 88%甲酸从该茯苓菌丝体中提取出四种多糖 ,编号为PCM1 ,PCM2 ,PCM3和PCM4 .用红外光谱 (IR) ,高效液相色谱 (HPLC) ,气相色谱 (GC)及13 C 核磁共振 ( 13 C NMR)等方法分析了它们的组成和结构 .结果表明 ,PCM1 ,PCM2为酸性杂多糖由D 鼠李糖、D 木糖、D 甘露糖、D 半乳糖、D 葡萄糖及葡萄糖醛酸组成 .PCM3主要为线型 β ( 1→ 3 ) D 葡聚糖 ,其产率占茯苓菌丝体总量的 55 8% .PCM4由D 葡萄糖和葡萄糖醛酸组成 .茯苓菌丝体化学组成和结构基本同于茯苓菌核多糖 ,随提取过程进行葡萄糖含量逐渐增加的变化规律也相同 .     

Synthesis of heparin saccharides IV. Synthesis of disaccharides possessing the structure of a repeating unit of heparin.

The synthesis of disaccharides possessing the structure of a repeating unit of heparin is reported. 2-Acetamido-2-deoxy-4-O-(methyl α-D-glucopyranosyluronate)-D-glucopyranose ( 1 ) and 2-[1-(benzyloxy)formamido]-2-deoxy-4-O-(methyl α-D-glucopyranosyluronate)-D-glucopyranose ( 2 ) have been prepared by two routes, (a) from D-glucose and D-glucosamine, and (b) from D-glucuronolactone and D-glucosamine.     

A new class of fluorescent boronic acids that have extraordinarily high affinities for diols in aqueous solution at physiological pH

The boronic acid group is an important recognition moiety for sensor design. Herein, we report a series of isoquinolinylboronic acids that have extraordinarily high affinities for diol-containing compounds at physiological pH. In addition, 5- and 8-isoquinolinylboronic acids also showed fairly high binding affinities towards D-glucose (K(a)=42 and 46 M(-1), respectively). For the first time, weak but encouraging binding of cis-cyclohexanediol was found for these boronic acids. Such binding was coupled with significant fluorescence changes. Furthermore, 4- and 6-isoquinolinylboronic acids also showed the ability to complex methyl α-D-glucopyranose (K(a)=3 and 2 M(-1), respectively).     

Asymmetric synthesis of 2-aminonorbornane-2-carboxylic acids by Diels-Alder reaction

The reaction between methyl N-acetyl-,β-didehydroalaninate and cyclopentadiene in the presence of several chiral Lewis acids is studied and the results obtained are compared with those described for the reactions of the same diene with chiral N-acetyl-,β-didehydroalaninates. In the presence of the titanium complex 24d methyl (1R,2R,4R) 2-acetamido-5-norbornen-2-carboxylate is preferably obtained. Thus, the reaction between methyl N-acetyl-(,β-didehydroalaninate and cyclopentadiene is a good method for the synthesis of (1S, 2R, 4R) 2-aminonorbomane-2-carboxylic acid.     

Macromolecular synthesis from saccharic lactones. Polyaddition of D-glucaro- and D-mannaro- 1,4:6, 3-dilactones with diisocyanates and hydrolyzability of the resulting polyurethanes having dilactone rings in the main chains

Polyaddition of saccharic acid dilactones prepared from D-glucose and D-mannitol, D-glu-caro-, and D-mannaro-1,4:6,3-dilactones ( 1 and 2 , respectively), with hexamethylene di-isocyanate ( 3a ) and methyl (S)-2,6-diisocyanatocaproate ( 3b ) was carried out by using dibutyltin dilaurate as a catalyst at 50, 25, and 0°C to give polyurethanes ( 4 and 5 ) having dilactone moieties in the main chains. The resulting polymers were found to decompose easily in phosphate buffers under neutral or slightly basic conditions (pH 7 or 8). Therefore, the polyurethanes may be used as novel degradable polymeric materials. © 1995 John Wiley & Sons, Inc.     

Stereoselective synthesis of highly enantioenriched 3-methyl-2-cyclohexen-1-ones possessing an asymmetric quaternary carbon as C-4 or C-6: a sugar template approach

The 1,4-addition of the enolate generated from α-methylated acetoacetate incorporated at C-4 of methyl 6-deoxy-2,3-di-O-(tert-butyldimethylsilyl)-α-d-glucopyranoside to methyl vinyl ketone, followed by aldol condensation of the resulting 1,4-addition product under two base-mediated conditions, provided 4-O-functionalized d-glucose derivatives with high diastereoselectivity. These products install a 3-methyl-2-cyclohexen-1-one-4- (or -6-) carboxylic acid as the O-4 ester, in which C-4 or C-6 is an asymmetric quaternary carbon. Removal of the sugar template from those aldol condensation products provided synthetically useful 3,6-dimethyl-2-cyclohexen-1-one-6-carboxylic acid and 3,4-dimethyl-2-cyclohexen-1-one-4-carboxylic acid derivatives both in high enantioenriched forms.     

1-甲基-2-苯基吲哚的琥红敏化单重态氧反应

1-甲基-2-苯基吲哚(1)在甲醇中的琥红(RB)敏化单重态氧反应生成1-甲基-2-甲基氧-2-苯基-1, 2-二氢-3H-吲哚-3-酮(4)和1-甲基-2-羟基-2-苯基-1, 2-二氢-3H-吲哚-3-酮(6), 后者在强碱性介质下发生苯乙醇酸型重排生成1-甲基-3-羟基-3-苯基氧化吲哚(14)。研究了6的溶剂分解反应以及外加碱对光氧化反应的影响。探讨了光氧化产物的形成途径。结果表明: 4系两性离子中间体2的溶剂捕获、脱水产物, 而6则系二氧杂环丁烷中间体7的裂解、抽氢产物。     

Reactions of hydro(pero)xy derivatives of polyunsaturated fatty acids/esters with nitrite ions under acidic conditions. Unusual nitrosative breakdown of methyl 13-hydro(pero)xyoctadeca-9,11-dienoate to a novel 4-nitro-2-oximinoalk-3-enal product

13(S)-hydroperoxy- and 13(S)-hydroxyoctadeca-9,11-dienoic acids (1a/b), 15(S)-hydroperoxy- and 15(S)-hydroxyeicosa-5,8,11,13-tetraenoic acids (2a/b), and their methyl esters reacted smoothly with NO2- in phosphate buffer at pH 3-5.5 and at 37 degrees C to afford mixtures of products. 1b methyl ester gave mainly the 9-nitro derivative 3b methyl ester (11% yield) and a peculiar breakdown product identified as the novel 4-nitro-2-oximinoalk-3-enal derivative 4 methyl ester (15% yield). By GC-MS hexanal was also detected among the products. Structures 3b and 4 methyl esters were secured by 15N NMR analysis of the products prepared from 1b methyl ester upon reaction with Na15NO2. 4 methyl ester (14% yield) was also obtained from 1a methyl ester along with the nitrated hydroperoxy derivative 3a methyl ester (10% yield). Under the same conditions, 2a/b methyl esters gave mainly the corresponding nitrated derivatives 5a/b, with no detectable breakdown products, whereas the model compound (E,E)-2,4-hexadienol (6) afforded two main nitrated derivatives identified as 7 and 8. A reaction pathway for 1a/b methyl esters was proposed involving conversion of nitronitrosooxyhydro(pero)xy intermediates which would partition between two competing routes, viz., loss of HNO2, to give 3a/b methyl esters, and a remarkably facile fission leading to 4 methyl ester and hexanal.     

Preparation and Characterization of the Enzymatic Degradation Products of the Exopolysaccharide From Klebsiella K13

Oligosaccharides were prepared from the exopolysaccharide of Klebsiella K13 by enzymatic degradation and characterized. A phage-borne depolymerase enzyme was used to degrade the exopolysaccharide of Klebsiella K13. Bio-Gel P4 and P6 were used to purify the oligosaccharide products. The purified oligosaccharides were characterized by HPLC, mass spectroscopy, infrared spectroscopy, and NMR spectroscopy. The monosaccharide constituents of these enzymatic degradation products include D-glucose, D-galactose, D-mannose, and D-glucuronic acid. It was concluded that a pentasaccharide repeating unit with the following structure, as well as its dimer and trimer, was released from the exopolysaccharide: 3,4-O-(1-carboxyethylidene)-β-D-Galp-(1→4)-α-D-GlcpA-(1→3)-β-D-Manp-(1→4)-α-D-Glcp-(1→3)-D-Glcp     

Chemistry of sulfonyl isocyanates and sulfonyl isothiocyanates. X. Possible routes to substituted imidazolidinethiones and hexahydropyrimidinethiones

4-Toluenesulfonyl isocyanate (I) reacted with 2-aminoethanol and 3-amino-l-propanol to give 2:1 isocyanate/amino alcohol addition products. 1-Amino-2-propanol and I gave 1:1 and 2:1 adducts while 2-amino-2-methyl-l-propanol afforded only a 1:1 adduct. 4-Toluenesulfonyl isothio-cyanate (III) gave 1:1 adducts with 2-aminoethanol, l-amino-2-propanol and 3-amino-l-propanol, the first two of which were cyclized by concentrated sulfuric acid to 1-(4-toluenesulfonyl)-imidazoline-2-thiones and the third to 1-(4-toluenesulfonyl)hexahydropyrimidine-2-thione. A 1:2 adduct was obtained from III and 2-amino-2-methyl-l-propanol. Amino acids reacted with I and with 4-chlorobenzenesulfonyl isocyanate (II) to give N-(arylsulfonyl)-N¹-(carboxylic acid)-ureas. N-(4-Toluenesulfonyl)-N¹-(acetic acid)-urea (XVI) was converted to the methyl ester (XIX) by concentrated sulfuric acid and methanol and to water-soluble unrecoverable products by sulfuric acid alone. Glycine and III gave N-(4-toluenesulfonyl)-N¹-(acetic acid)-thiourea (XX) which was converted to the methyl ester (XXII) by concentrated sulfuric acid/methanol and to the cyclic 1-(4-toluenesulfonyl)imidazolin-5-one-2-thione (XXI) by sulfuric acid alone.