Synthesis, structure, and biological activity of ferrocenyl carbohydrate conjugates

Seven ferrocenyl carbohydrate conjugates were synthesized. Coupling reactions of monosaccharide derivatives with ferrocene carbonyl chloride produced {6-N-(methyl 2,3,4-tri-O-acetyl-6-amino-6-deoxy-alpha-D-glucopyranoside)}-1-ferrocene carboxamide (3), {1-O-(2,3,4,6-tetra-O-benzyl-D-glucopyranose)}-1-ferrocene carboxylate (4), and {6-O-(1,2,3,4-tetra-O-acetyl-beta-D-glucopyranose)}-1-ferrocene carboxylate (5). Similarly, 1,1'-bis(carbonyl chloride)ferrocene was coupled with the appropriate sugars to produce the disubstituted analogues bis{6-N-(methyl 2,3,4-tri-O-acetyl-6-amino-6-deoxy-alpha-D-glucopyranoside)}-1,1'-ferrocene carboxamide (8), bis{1-O-(2,3,4,6-tetra-O-benzyl-D-glucopyranose)}-1,1'-ferrocene carboxylate (9), and bis{6-O-(1,2,3,4-tetra-O-acetyl-beta-D-glucopyranose)}-1,1'-ferrocene carboxylate (10). {6-N-(Methyl-6-amino-6-deoxy-alpha-D-glucopyranoside)}-1-ferrocene carboxamide monohydrate (12) was synthesized via amide coupling of an activated ferrocenyl ester with the corresponding carbohydrate. All compounds were characterized by elemental analysis, 1H NMR spectroscopy, and mass spectrometry. X-ray crystallography confirmed the solid-state structure of three ferrocenyl carbohydrate conjugates: 2-N-(1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-D-glucopyranose)-1-ferrocene carboxamide (1), 1-S-(2,3,4,6-tetra-O-acetyl-1-deoxy-1-thio-D-glucopyranose)-1-ferrocene carboxylate (2), and 12. The above compounds, along with bis{2-N-(1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-D-glucopyranose)}-1,1'-ferrocene carboxamide (6), bis{1-S-(2,3,4,6-tetra-O-acetyl-1-deoxy-1-thio-D-glucopyranose)}-1,1'-ferrocene carboxylate (7), and 2-N-(2-amino-2-deoxy-D-glucopyranose)-1-ferrocene carboxamide (11) were examined for cytotoxicity in cell lines (L1210 and HTB-129) and for antimalarial activity in Plasmodium falciparum strains (D10, 3D7, and K1, a chloroquine-resistant strain). In general, the compounds were nontoxic in the human cell line tested (HTB-129), and compounds 4, 7, and 9 showed moderate antimalarial activity in one or more of the P. falciparum strains.     

1-芳酰基-4-(1＇-N-β-D-吡喃型糖基)氨基硫脲类化合物的合成

通过2,3,4,6-四-O-乙酰基-β-D-吡喃型葡萄糖异硫氰酸酯和2,3,4-三-O-乙酰基-β-D-吡喃型木糖异硫氰酸酯与取代的芳基酰肼的亲核加成反应合成了10个1-芳酰基-4-(1＇-N-2＇,3＇,4＇,6＇-四-O-乙酰基-β-D-吡喃型葡萄糖基)氨基硫脲和7个1-芳酰基-4-(1＇-N-2＇,3＇,4＇-三-O-乙酰基-β-D-吡喃型木糖基)氨基硫脲,所得化合物的结构经元素分析,IR,1H NMR确证.     

Synthesis of N-Hetarylthiourea Derivatives of Carbohydrates

ABSTRACT

The syntheses of N-hetaryl (thiazole-2-yl, 2-thiazoline-2-yl, 4,4-diphenyloxazoline-2-yl, cis-3a,4,5,6,7,7a-hexahydrobenzoxazole-2-yl)-N′-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl) thioureas (1a-1d), N-hetaryl (2-thiazoline-2-yl, 4,4-diphenyloxazoline-2-yl)-N′-(2,3,4,6-tetra-O-benzoyl-β-D-galactopyranosyl) thioureas (2b, 2c) and 1,2,3,4,6-tetra-O-acetyl-2-deoxy-2-[3-(4′, 4′-diphenyl-2′-y1) thioureido]-β-D-glucopyranose (3c) are described. The structures and conformational properties of prepared compounds are based on analytical and spectroscopic (UV, IR, NMR and MS) data.     

Stereoselective synthesis of the alpha-glycoside of a KDO "C"-disaccharide

The reaction of tert-butyl (4,5,7, 8-tetra-O-acetyl-3-deoxy-alpha-D-manno-2-octulopyranosyl chloride)onate donor 7 with the 6-formylgalactopyranoside acceptor 4 in the presence of SmI(2) provided only the KDO alpha-C-disaccharide 8. The bulky tert-butyl ester in the donor was used to reverse the stereochemical outcome of C-glycosylation, stereoselectively forming the alpha-"C"-disaccharide of KDO.     

Unexpected matrix interactions in liquid secondary ion mass spectrometry of two pyranosyl mercaptans

An unexpected interaction with a thioglycerol matrix appeared in the liquid secondary ion mass spectrometry (LSIMS) spectra of two pyranosyl mercaptans [2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranose (1a) and 2,3,4,6-tetra-O-acetyl-1,5-dithio-β-D-glucopyranose (1b)] often used to prepare glucosinolates, important thiosaccharidic metabolites found in all plants of the order Brassicales. The reactions, probably occurring in the solvent cage, seem to involve radical mechanisms.     

Polymer Supported Synthesis of 2,3,4,6-Tetra-O-Acetyl-β-D-Glucopyranosyl Esters of Aromatic Carboxylic Acids

Aromatic carboxylic acids bound to Amberlyst A-26 react with α-acetobromoglucose to form 2,3,4,6-tetra-O-acetyl-1-0-aroyl-β-D-glucopy ranose derivatives in good yield. Glucosylation occurs satisfactorily with carboxylic acids and nitrophenols (pKa 7–4), but not with phenols whose pKa values are higher (pka ～ 10). Selective glucosylation at the carboxylic group is easily achieved in the case of phenolic acids.     

Synthesis of Trisaccharide of Incanosides from Caryopteris incana

Recent evidence has accumulated suggesting that free radicals are involved in many deterioration processes. They attack the unsaturated fatty acids in the biomembranes resulting in membrane lipid peroxidation, which is strongly connected with aging, carcinogenesis and atherosclerosis.[1] Free radicals also attack DNA and cause mutation leading to cancer.[2] Thus it is desirable to look for effective radical scavengers. In 1999, Gao et al.[3] isolated incanosides C, D and E from the whole plant of Caryopteris incana (THUNB.). These natural products were proved to exhibit good radical scavenging activities against DPPH radical and inhibitory activities against the oxidation of linoleic acid.[4] Herein, for the first time we report the synthesis of trisaccharide phenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl-(1→2)-3,4-di-O-benzoyl-α-L-rhamno-pyranosyl-(1→3)-2-O-acetyl-4,6-O-benzylidene-1-thio-β-D-glucopyranoside (1), which is the common carbohydrate moiety of incanosides C, D and E.     

Synthesis of a teichoic acid fragment of bacillus var.niger w.m. by a phosphotriester approach

Three properly-protected derivatives, one non-terminal and two terminal units, of 3-0-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-sn-glycerol have been joined together by two interglyceridic (2→1) phosphotriester linkages to afford, after removal of all protective groups, a teichoic acid fragment.     

An Easy Preparation of 2-Deoxy-2-Phthalimido-β-D-Glucoand β-L-Rhamnopyranosides

Abstract

Benzyl and allyl glycosides are prepared directly from 1,3,4,6-tetra-O-acetyl-2-deoxy-2-phthalimido-α,β-d-glucppyranose and 1,2,3,4-tetra-O-acetyl-β-l-rhamnopyranose using stannic chloride as catalyst with solutions of the respective alcohols in methylene chloride.     

Combined Chemical and Enzymatic Synthesis of a Disialylated Tetrasaccharide Analogous to M and N Bloodgroup Determinants of Glycophorin a

Abstract

Reaction of 2,3,4,6-tetra-O-acetyl-α-D-galactopyraaosyl bromide (1) with phenyl 2-acetamido-2-deoxy-4,6-O-(4-methoxy-benzylidene)-α-D-galactopyranoside (3) mediated by mercuric salts, followed by removal of the 4-methoxybenzylidene group and O-deacylation afforded phenyl 2-acetamido-2-deoxy-3-O-p-D-galactopyranosyl-α-D-galactopyranoside (6). Compound 6 was used as a substrate for the selective introduction of two neuraminic acid residues with partially purified sialyltrans-ferase preparations. First, disaccharide 6 was treated with CMP-[¹⁴c]-NeuAc as donor substrate and CMP-NeuAc: Gal-p(l-3)-GalNac-a(2-3)sialyltransferase from human placenta to afford trisaccharide 7 (yield 85X), sialylated at C-3 of the galactose residue. Treatment of 7 with CMP-[³H]-NeuAc and a micro-somal fraction from regenerating rat liver, containing the CMP-NeuAc: NeuAc-a(2-3)-Gal-p(l-3)GalNAc-α(2-6) sialyltrans-ferase activity, gave the disialylated tetrasaccharide 8 in 10X yield.     

5-甲基-1,2,4-三唑-3-硫酮类糖苷化合物的合成及抗菌活性

在KOH/丙酮体系中, 以5-甲基-4-N-取代苯基亚胺/胺基-1,2,4-三唑-3-硫酮为原料, 与溴-α-D-四乙酰葡萄糖进行Kenigs-Knorr反应合成了10个新颖的化合物—5-甲基-4-N-取代苯基亚胺基/胺基-3-S-(2',3',4',6'-四-O-乙酰基-β-D-吡喃葡萄糖基)-1,2,4-三唑(2a~2e, 5a~5e); 并在二氯甲烷/甲醇/甲醇钠混合体系中水解脱除乙酰基, 得到10个新颖的化合物—5-甲基-4-N-取代苯基亚胺基-3-S-(β-D-吡喃葡萄糖基)-1,2,4-三唑(3a~3e)及5-甲基-4-N-取代苯基胺基-3-S-(β-D-吡喃葡萄糖基)-1,2,4-三唑(6a~6e). 化合物的结构均经核磁共振波谱(NMR)、 红外光谱(IR)和高分辨质谱(HRMS)分析确证. 生物活性测试结果表明, 目标化合物对大肠杆菌、 金黄色葡萄球菌、 枯草芽孢杆菌和白色念珠球菌普遍具有较好的抗菌活性. 化合物3d和3e对4种菌株的最小抑菌浓度相对较低, 表现出较强的广谱抗菌活性.     

烷基4-(2,3,4,6-四-O-乙酰基-β-D-吡喃半乳糖基)-2,3-二-O-乙酰基-β-D-吡喃葡萄糖苷的快速合成

寡糖是生物体内重要的信息物质,参与细胞之间的通讯、识别、信号传递等过程[1],且在病原与宿主细胞的相互作用中也担当重要角色[2,3].Raz和Laton发现,乳糖能抑制人黑色素瘤(A375,SH4,Hs94,Hs852,Hs939)、人颈部腺瘤Hela-S3、鼠黑色素瘤B16-F1和鼠恶性纤维瘤UV-2237P等的同型细胞粘着作用[4-9].     

CuI/TMEDA催化合成芳基葡萄糖碳苷化合物

以THF为溶剂, CuI/TMEDA为催化剂,四乙酰溴代葡萄糖与芳基溴化镁经取代反应合成了芳基葡萄糖碳苷（2a~2c）,其结构经¹H NMR和¹³C NMR确证。该方法立体选择性较好。在最佳反应条件(THF为溶剂,10% CuI和10% TMEDA为催化剂,于0 ℃反应至终点)下,2a~2c的收率为58%~71%, α/β为1/6.5~1/7.1。     

N-取代-N'-(2', 3', 4', 6'-四-O-乙酰基-β-D-吡喃葡萄糖基) (酰)氨基硫脲 的合成

利用2,3,4,6-四-O-乙酰基-β-D-吡喃葡萄糖异硫氰酸酯(Ⅰ)分别和芳酰肼(Ⅱ),2-氨基-5-烷基/芳基-1,3,4-噻二唑(Ⅲ),3-烷基/芳基-4-氨基-5-巯基-1,2,4-三唑(Ⅳ),O,O-二烷基(硫代)磷酰肼(Ⅴ,Ⅵ)反应,制得了目标物1a～1c,2d～2e,3f～3i,4j～4k和5l等12种新化合物,IR,^1HNMR和MS分析结果证明产物为β构型。     

Synthetic Studies on Sialoglycoconjugates 16: α-Predominant Glycoside Synthesis of N-Acetylneuraminic Acid With the Primary Hydroxyl Group in Carbohydrates Using Dimethyl(Methylthio)Sulfonium Triflate as a Glycosyl Promoter

ABSTRACT

Coupling of the primary hydroxyl group in the suitably protected 2-(trimethylsilyl)ethyl glycosides of D-glucopyranose (3), N-acetyl-D-glucosamine (7), N-acetyl-D-galactosamine (9), D-lactose (10), and N-acetylneuraminic acid (11), with methyl (methyl 5-acetamido-4, 7,8, 9-tetra-O-acetyl-3, 5-dideoxy-2-thio-D-glycero-α-D-galacto-2-nonulopyranosid)onate (12) as the glycosyl donor in acetonitrile in the presence of dimethyl(methylthio)sulfonium triflate (DMTST) as a glycosyl promoter and molecular sieves 3A, gave predominantly the corresponding α-glycosides 13, 15, 17, 25, and 29 of N-acetylneuraminic acid in 43-71% yields, respectively, together with the ß-glycosides (13-24%).     

HClO4 x SiO2 catalysed synthesis of alkyl 3-deoxy-hex-2-enopyranosides from 2-hydroxy glucal ester: application in the synthesis of a cis-fused bicyclic ether and a 4-amino-C-glucoside

A variety of alcohols react with 2,3,4,6-tetra-O-acetyl-1,5-anhydro-D-arabino-hex-1-enopyranose 1 in the presence of a catalytic amount of HClO(4) supported on silica gel to give the corresponding alkyl 3-deoxy-hex-2-enopyranosides 2 in high yield, with short reaction times (10-45 mins) and good alpha-selectivity. Work-up merely involves filtration of the reagent, followed by chromatographic purification of the crude product. This methodology has also been employed in the synthesis of a bicyclic ether, a useful precursor for cyclic polyethers, and a 4-amino-C-glucoside.     

Synthetic Studies on Sialoglycoconjugates 27: Synthesis of Sialyl-α(2→6)-Lewis X

ABSTRACT

Synthesis of a positional isomer of sialyl Lewis X with regard to the substitution of the terminal galactose residue of the pentasaccharide by N-acetylneuraminic acid is described. Dimethyl(methylthio)sulfonium triflate-promoted coupling of 2-(trimethylsilyl)ethyl O-(2,3,4-tri-O-benzyl-α-L-fucopyranosyl)-(1→3)-O-(2-acetamido-6-O-benzyl-2-deoxy-ß-D-glucopyranosyl)-(1→3)-O-(2,4,6-tri-O-benzyl-ß-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-ß-D-glucopyranoside (1) with methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→6)-2,4-di-O-benzoyl-3-O-benzyl-1-thio-ß-D-galactopyranoside (2) gave the desired hexasaccharide 3. Compound 3 was converted into the α-trichloro-acetimidate 6, via reductive removal of the benzyl groups, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, and treatment with trichloro-acetonitrile, which, on coupling with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (7), gave the ß-glycoside 8. Finally, 8 was transformed, via selective reduction of the azide group, coupling with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester group, into the title ganglioside 11 in good yield.     

The Purification of Glucose Type Glycosyl Nitrate and the Synthesis of Spacer—armed N—Acetyllactosamines and Their Dimers

Our previous paper1,2reported the results of selective synthesis of mannose type glycosides and their dimers in our attempt to synthesize derivatives of N-acetyllacto- samine, which could have potential activity of anti-metastasis3. Further studies on the glycosylation of the accepters exploiting glycosyl nitrate instead of the acetate as donor showed interesting chemoselectivity between the two kinds of donor, namely, the glucose type and the mannose type. The reactivity difference of the t…     

2,3,4,6-四-O-乙酰基-β-D-吡喃葡萄糖基异硫氰酸酯的合成及晶体结构

采用葡萄糖作原料经乙酰化、溴化和硫氰酸化三步合成了2,3,4,6-四-O-乙酰基-β-D-吡喃葡萄糖基异硫氰酸酯,培养出了单晶,用X射线衍射分析了其晶体结构.结果表明,晶体为正交晶系,P212121空间群,a=0.72624(2)nm,b=1.17508(2)nm,c=2.17210(5)nm,α=β=γ=90°,V=1.85365(7)nm,Z=4,R=0.0531,wR=0.1359.     

N,N-二取代甘氨酸四乙酰基葡萄糖酯的合成与表征

在碳酸钾和十六烷基三甲基溴化铵存在下, 将N-(N-乙酰基-N-芳氨基乙酰基)-N-芳氨基乙酸与全乙酰化α-溴代葡萄糖反应合成出了7个新的N,N-二取代甘氨酸四乙酰基葡萄糖酯(5a～5g), 并利用IR, 1H NMR, MS和元素分析对其结构进行了表征.