Synthesis of alpha-(2-->5)Neu5Gc oligomers

A facile synthesis of the sialic acid oligomers alpha-(2-->5)Neu5Gc (1) is presented. Monosaccharides 2-4 with suitable functionality were used as the building blocks. After selective removal of the paired carboxyl and amine protecting groups, the fully protected oligomers were assembled through consecutive coupling of the building blocks by well established peptide coupling techniques. By this approach, fully protected oligomers as large as an octasaccharide were synthesized. Deprotection of these fully protected oligomers was conducted in two steps (LiCl in refluxing pyridine and 0.1 n NaOH) to afford the desired products in high yield. Enzymatic degradation of the octamer with neuraminidase, monitored by capillary electrophoresis (CE), was also accomplished. The stepwise exo-cleavage adducts were all well separated and identified in the CE spectrum. The strategy described here for solution-phase synthesis also provides the basis for future solid-phase synthesis of poly-alpha-(2-->5)Neu5Gc.     

Synthesis of oligomers derived from amide-linked neuraminic acid analogues

N-Fluoren-9-ylmethoxycarbonyl-protected sugar amino acids derived from alpha-O-methoxy- and 2,3-dehydroneuraminic acids have been prepared. Incorporation of these monomer units into solid-phase synthesis led to the efficient synthesis of two series of oligomers varying from one to eight units in length. The (1-->5)-linked amides of 2,3-dehydroneuraminic acid were further subjected to hydrogenation giving a third series of oligomers with a beta-hydrido substituent at the anomeric carbon.     

Preparation of glycyrrhetic acid glycosides having various beta(1----2)-linked disaccharides and their cytoprotective effects on carbon tetrachloride-induced hepatic injury.

Glycyrrhetic acid glycosides (1-7) having beta(1----2)-linked disaccharides such as 2-O-beta-D-glucopyranosyl-beta-D-galactopyranose, 2-O-beta-D-galactopyranosyl-beta-D-galactopyranose, 2-O-beta-D-glucuronopyranosyl-beta-D-galactopyranose, 2-O-beta-D-glucopyranosyl-beta-D-glucuronopyranose, 2-O-beta-D-galactopyranosyl-beta-D-glucuronopyranose, 2-O-beta-D-galactopyranosyl-beta-D-glucopyranose, 2-O-beta-D-glucuronopyranosyl-beta-D-glucopyranose, respectively, were synthesized by stepwise construction; from glycyrrhetic acid monoglycosides to the diglycosides. The cytoprotective activities of the glycosides 1-7 and 2-O-(beta-D-glucopyranosyl)-beta-D-glucopyranosyl-11-oxoolean-12-e n-30-oate (8) were compared with natural occurring glycyrrhizin (9). Among these glycosides 1-8, glycosides 3 and 7 having beta-D-glucuronopyranose (glcUA) as the only terminal sugar component were more effective materials against hepatic injury than glycyrrhizin 9.     

L-乳酸齐聚物的制备及其三羰基铼衍生物的合成

以L-丙交酯为原料, 通过正交保护基对其羧基、羟基进行修饰, 合成并表征了乳酸3个系列的12个化合物. 同时以合成得到的乳酸六聚体为原料, 合成并表征了羟基封端的聚乳酸-聚乙二醇-三齿螯合剂系列化合物, 并将其与[Et₄N]₂[Re(CO)₃Br₃]配位合成了其冷标记三羰基铼配合物. 产物通过IR, ¹H NMR, ¹³C NMR, ESI-HRMS, MALDI-HRMS或元素分析进行了表征. 该方法为扩展聚乳酸化学修饰法在材料科学中的应用奠定了基础. 此外分子量可控的乳酸-乙二醇结构铼配合物的设计合成扩展了其在分子影像科学的应用.     

Tandem Intramolecular Benzyne-Furan Cycloadditions. Total Synthesis of Vineomycinone B(2) Methyl Ester

We have exploited tandem intramolecular benzyne-furan cycloadditions employing three different benzyne precursors to generate substituted bisoxabenzonorbornadienes in a single operation. The regiochemical outcomes in these Diels-Alder reactions were effectively controlled by using disposable silicon tethers to link the reacting benzyne and furan moieties. Two different methods for converting the intermediate bisoxabenzonorbornadienes to substituted anthrarufins were developed. The first tactic entails the initial cleavage of the silicon tethers followed by regioselective ring opening of the oxabicycloheptadienes and oxidation of the central ring giving the target anthrarufin, whereas the second features the regioselective ring opening of the oxabicycloheptadienes followed by protiodesilylation and oxidation. When the starting furans bear carbohydrate substitutents, this new methodology enables the rapid assembly of the glycosyl-substituted aromatic cores of complex C-aryl glycoside antibiotics from simple starting materials. The utility of this novel approach to anthrarufins and C-aryl glycosides is exemplified in a triply convergent synthesis of vineomycinone B₂ methyl ester.     

First Synthesis of a Series of New Natural Glucosides

Alkyl glucoside 1 and aryl glycosides 2-4 were highly stereospecifically synthesized over 4-6 steps from commercially available starting materials. The coupling reaction of the acetobromo-α-D-glucose with the unprotective dihydroxy aglycon in the presence of silver oxide, or with aromatic aglycon in the presence of sodium hydroxide produced the key intermediate. Only β-configuration glycosides were formed in this procedure. The synthesis of all these glycosides was reported for the first time.     

Highly efficient total synthesis of the marine natural products (+)-avarone, (+)-avarol, (-)-neoavarone, (-)-neoavarol and (+)-aureol

Biologically important and structurally unique marine natural products avarone (1), avarol (2), neoavarone (3), neoavarol (4) and aureol (5), were efficiently synthesized in a unified manner starting from (+)-5-methyl-Wieland-Miescher ketone 10. The synthesis involved the following crucial steps: i) Sequential BF(3)Et(2)O-induced rearrangement/cyclization reaction of 2 and 4 to produce 5 with complete stereoselectivity in high yield (2 --> 5 and 4 --> 5); ii) strategic salcomine oxidation of the phenolic compounds 6 and 8 to derive the corresponding quinones 1 and 3 (6 --> 1 and 8 --> 3); and iii) Birch reductive alkylation of 10 with bromide 11 to construct the requisite carbon framework 12 (10 + 11 --> 12). An in vitro cytotoxicity assay of compounds 1-5 against human histiocytic lymphoma cells U937 determined the order of cytotoxic potency (3 > 1 > 5 > 2 > 4) and some novel aspects of structure-activity relationships.     

Interrupted Pummerer Reaction in Latent‐Active Glycosylation: Glycosyl Donors with a Recyclable and Regenerative Leaving Group

Latent O‐glycosides, 2‐(2‐propylthiol)benzyl (PTB) glycosides, were converted into the corresponding active glycosyl donors, 2‐(2‐propylsulfinyl)benzyl (PSB) glycosides, by a simple and efficient oxidation. Treatment of the PSB donor and various acceptors with triflic anhydride provided the desired glycosides in good to excellent yields. The leaving group, which was activated by an interrupted Pummerer reaction, can be recycled (PSB‐OH) and regenerated as the precursor (PTB‐OH). A natural hepatoprotective glycoside, leonoside F, was efficiently synthesized in a convergent [3+1] manner with this newly developed method. The present total synthesis also led to a structural revision of this phenylethanoid glycoside.     

New flavonoid glycosides from the leaves of Solidago altissima

Two new flavonoid glycosides kaempferol 3-O-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside (1), and quercetin 3-O-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside (2), together with six known flavonoid glycosides were isolated from the leaves of Solidago altissima L. grown in Kochi of Japan. The structure elucidation of the isolated compounds was performed by acid hydrolysis and spectroscopic methods including UV, IR, ESI-MS, 1D- and 2D-NMR experiments.     

New pregnane glycosides from Cynanchum ascyrifolium

Two new pregnane glycosides, cynascyrosides D and E, were isolated from the roots of Cynanchum ascyrifolium. The structures of these compounds were determined on the basis of spectroscopic and chemical evidence as cynajapogenin A 3-O-alpha-L-cymaropyranosyl-(1-->4)-beta-D-digitoxopyranosyl-(1-->4)-beta-L-cymaropyranoside and cynajapogenin A 3-O-beta-D-glucopyranosyl-(1-->4)-alpha-L-diginopyranosyl-(1-->4)-beta-L-cymaropyranosyl-(1-->4)-beta-D-digitoxopyranoside.     

Chemical synthesis of linear and cyclic unnatural oligosaccharides by iterative glycosidation of ketoses

The development of an efficient method for the stereoselective synthesis of alpha-D-(2-->1)-linked ketoside oligomers is described. The method is based on an iterative protocol composed of two key steps: a) the coupling of a thiazolylketosyl phosphite donor with an hydroxymethylketoside acceptor; and b) the introduction of the hydroxy-methyl group at the anomeric carbon atom of the resulting oligomer. To highlight its efficiency, the protocol was used in the assembly of D-galacto-2-heptulopyranose-containing oligoketosides through alpha-(2-->1) linkages up to the pentameric stage. The yield of the isolated oligomers ranged from 48 % in the first cycle to 29% in the fourth cycle. Having employed a pentenyl-substituted hydroxymethylketoside acceptor in the first cycle, all the derived oligomers contained the pentenyl group at their reducing end. This group was exploited to transform the linear oligomers into cyclic products through intramolecular glycosidation. The major product derived from the linear trisaccharide was confirmed by X-ray crystallography to be the cyclotris-(2-->1)-(alpha-D-galacto-2-heptulopyranosyl). The structure of this compound was essentially that of a [9]crown-3 ether bearing three galactopyranose rings spiroanellated in a propellerlike fashion. This arrangement of carbohydrate units linked to the crown ether created a densely alkoxylated cavity suitable for the encapsulation of alkali-metal cations (Li, Na, K, Ca, Mg).     

Oligomeric Alkoxysilanes with Cagelike Hybrids as Cores: Designed Precursors of Nanohybrid Materials

Well‐defined alkoxysilane oligomers containing a cagelike carbosiloxane core were synthesized and used as novel building blocks for the formation of siloxane‐based hybrid networks. These oligomers were synthesized from the cagelike trimer derived from bis(triethoxysilyl)methane by silylation with mono‐, di‐, and triethoxychlorosilanes ((EtO)_nMe_3?nSiCl, n=1, 2, and 3). Hybrid xerogels were prepared by hydrolysis and polycondensation of these oligomers under acidic conditions. The structures of the products varied depending on the number of alkoxy groups (n). When n=2 and 3, microporous xerogels (BET surface areas of 820 and 510 m² g^?1, respectively) were obtained, whereas a nonporous xerogel was obtained when n=1. ²⁹Si NMR spectroscopic analysis suggested that partial rearrangement of the siloxane networks, which accompanied the cleavage of the Si–O–Si linkages, occurred during the polycondensation processes. By using an amphiphilic triblock copolymer surfactant as a structure‐directing agent, hybrid thin films with a 2D hexagonal mesostructure were obtained when n=2 and 3. These results provide important insight into the rational synthesis of molecularly designed hybrid materials by sol–gel chemistry.     

Synthesis and biological evaluation of phosphono analogues of capsular polysaccharide fragments from Neisseria meningitidis A

Neisseria meningitidis type A (MenA) is a Gram-negative encapsulated bacterium that may cause explosive epidemics of meningitis, especially in the sub-Saharan region of Africa. The development and manufacture of an efficient glycoconjugate vaccine against Neisseria meningitidis A is greatly hampered by the poor hydrolytic stability of its capsular polysaccharide, which is made up of (1-->6)-linked 2-acetamido-2-deoxy-alpha-D-mannopyranosyl phosphate repeating units. Since this chemical lability is a product of the inherent instability of the phosphodiester bridges, here we report the synthesis of phosphonoester-linked oligomers of N-acetyl mannosamine as candidates for stabilised analogues of the corresponding phosphate-bridged saccharides. The installation of each interglycosidic phosphonoester linkage was achieved by Mitsunobu coupling of a glycosyl C-phosphonate building block with the 6-OH moiety of a mannosaminyl residue. Each of the synthesised compounds contains an O-linked aminopropyl spacer at its reducing end (alpha- or beta-oriented) to allow for protein conjugation. The relative affinities of the synthetic molecules were investigated by a competitive ELISA assay and showed that a human polyclonal anti-MenA serum can recognise both the phosphonoester-bridged fragments 1-3 and their monomeric subunits, glycosides 20 and 21. Moreover, the biological results suggest that the abilities of these compounds to inhibit the binding of a specific antibody to MenA polysaccharide are dependent on the chain lengths of the molecules, but independent on the orientations of the anomeric linkers.     

Synthesis of alkyl glycosides from cyclodextrin using cyclodextrin glycosyltransferase from Paenibacillus sp. RB01

Alkyl glycosides have potential use as biodegradable detergents due to their high surface activity with low toxicity. Recent progress in the application of enzymes to the preparation of these surface-active compounds demonstrates the advantages to the chemical synthesis. In this work, alkyl glycosides were, for the first time, synthesized from cyclodextrin (CD) and various soluble alcohols by transglycosylation reaction using cyclodextrin glycosyltransferase (CGTase) from Paenibacillus sp. RB01. Several alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol and 2-butanol) as glycosyl-acceptor substrates were evaluated. It was found that the reaction products which were analyzed by TLC were maximum for 30% methanol, 20?C30% ethanol, 10?C20% 1-propanol, 10% 2-propanol, 8% 1-butanol and 5?C10% 2-butanol. In addition, the increase in the yield of alkyl glycoside formation was achieved by using methanol as an acceptor. Optimal reaction conditions for methyl glycoside synthesis from CD were to incubate 1.2% (w/v) ??-CD and 240 U/mL of CGTase in a water/methanol system containing 30% (v/v) methanol, pH 6.0 and a temperature of 40???C. At least three main methyl glycoside products were formed having 1?C3 monosaccharide units attached to methanol which were in accordance with the results of MS analysis.     

Synthesis of the glycopeptidolipid of Mycobacterium avium Serovar 4: first example of a fully synthetic C-mycoside GPL

The preparation of the glycopeptidolipid (GPL) present in the cell wall of Mycobacterium aviumSerovar 4, namely 3,4-di-O-Me-alpha-L-Rhap-(1-->1)[R-C(21)H(43)CH(OH)CH(2)CO-D-Phe-[4-O-Me-alpha-L-Rhap-(1-->4)-2-O-Me-alpha-L-Fucp-(1-->3)-alpha-L-Rhap-(1-->2)-6-deoxy-alpha-L-Talp-(1-->3)]-D-allo-Thr-D-Ala-L-Alaol] (1), is described. The synthesis was based on the disconnection of the final structure into four building blocks, an L-rhamnosyl pseudodipeptide, a 6-deoxy-L-talosyl dipeptide, a trisaccharide donor, and a 3-hydroxyalkanoic acid. The key steps are the creation of the glycosidic linkage between the trisaccharide donor, used as a pentenyl glycoside, and the 6-deoxy-L-talose unit of an appropriate D-Phe-O-(6-deoxy-L-talosyl)-D-allo-Thr derivative and the final coupling of the two glycodipeptide fragments. Pentenyl glycosides were shown to provide useful donors in several glycosylation steps. This work constitutes the first synthesis of the full structure of a so-called "polar mycoside C" GPL.     

Artificial DNAs based on alkynyl C-nucleosides as a superior scaffold for homo- and heteroexcimer emissions

DNA-like fluorescent oligomers composed of alkynyl beta-D-ribofuranosides bearing pyrene, perylene, and anthracene as a fluorophore were synthesized by solid-phase DNA synthesis. The fluorescent oligomers possess the defined number and order of the fluorophores. In these oligomers, the adjacent fluorophores efficiently interact with each other by hydrophobic interactions in their electronic ground states in a face-to-face fashion. The predominant excimer emissions were observed from not only the homooligomers (pyrene-pyrene and perylene-perylene systems) but also the heterooligomers (pyrene-perylene, pyrene-anthracene, and perylene-anthracene systems) in aqueous media.     

Oligomers of "extended viologen", p-phenylene-bis-4,4'-(1-aryl-2,6-diphenylpyridinium), as candidates for electron-dopable molecular wires

We report the synthesis and spectral characterization of the first five members of an oligomeric series built from alternating p-connected 1,4-benzene and 1,4-pyridinium rings, 1[n]-4[n], n=1-5, with p-phenylene-bis-4,4'-(1-aryl-2,6-diphenylpyridinium) ("extended viologen") as the repeating unit. The lengths of these rodlike molecules range from 2 to 9 nm. The monomer was obtained from p-phenylene-bis-4,4'-(2,6-diphenylpyrylium) (5) and p-phenylenediamine (6) or p-aminoacetanilide (9). Higher oligomers were synthesized by stepwise elaboration of the monomer by reactions with the appropriate bis-pyrylium (5) or pyrylium-phenylene-pyridinium (8) salts. Eight different counterions were used, and dodecamethylcarba-closo-dodecaborate was found to offer particularly favorable solubility characteristics. Ultraviolet absorption spectra of the oligomers suggest that the individual extended viologen segments interact only weakly, as a result of the strongly twisted orientation of the benzene rings that separate them. The UV spectrum of the monomer was interpreted by comparison with semiempirical INDO/S calculations performed at a DFT optimized geometry.     

Studies on the constituents from the aerial part of Baccharis dracunculifolia DC.

Ten new glycosides, named dracunculifosides A-J, were isolated along with sixteen known glycosides from the aerial part of Baccharis dracunculifolia DC. (Compositae). The structures of these glycosides were determined on the basis of spectral and chemical evidence. These new glycosides consisted of beta-D-glucopyranose or beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranose, and most possess an (E)-caffeoyl group.     

Studies on the constituents from the aerial part of Baccharis dracunculifolia DC. II

Ten new glycosides were obtained along with five known compounds from the aerial part of Baccharis dracunculifolia DC. (Compositae). The structures of these glycosides were determined based on spectral and chemical evidence. These new compounds consisted of beta-D-glucopyranose or beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranose, and most possessed an (E)-caffeoyl group the same as dracunculifosides A-J.     

A Facile Synthesis of 1,2-Anhydro-6-O-acetyl-3,4-di-O-benzyl-d-glycopyranoses and 1,2-Anhydro-5-O-acetyl-3-O-benzyl-D-glycofuranoses

The ability to couple carbohydrate entities to produce glycosides or higher oligomers is an important goal of synthetic organic chemistry.¹ For the past several decades, methods to construct glycosidic linkages have improved as a result of the development of glycosidation procedures.² However, owing to their structural complexity, synthesis of oligosaccharides is still a laborious task compared with the synthesis of oligopeptides and oligonucleotides. Many additional sugar derivatives which can improve and simplifjr synthetic procedures of oligosaccharides are needed.