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The selective oxidation of D-galactose to galactonic acid over Au/Al2O3 was studied isothermally in a semi-batch shaker reactor under pH-controlled conditions at atmospheric pressure. A series of Au/Al2O3 catalysts were prepared and calcined at different temperatures to achieve different gold-particle sizes. The catalytic properties of the gold nanoparticles were affected by the cluster size. A detailed comparison of activity and selectivity of these catalysts was made, which demonstrated that Au/Al2O3 with a mean particle size of 2.6 nm exhibited the highest activity. The influence of the pH value of the reaction medium on the selective oxidation of D-galactose was elucidated. Alkaline conditions were characterized by high catalyst activity and selectivity to aldonic acid. Inhibition of the catalytic activity was observed in the acidic medium. The intermediate species was present at low pH values, and this resulted in low conversion and selectivity to the main product, galactonic acid. The electrochemical potential of the catalyst was correlated to the catalytic activity.

Eight R2Sn(IV)-D-aldonate complexes [(R = Me, Bu; D-aldonate = D-galactonate2− (Galn), D-Gluconate2− (Glun), D-Gulonate2− (Guln), D-Ribonate2− (Ribn)], five of which are new derivatives, have been synthesized and structurally characterized both in solid and solution state by IR, 119Sn Mossbauer and 1H, 13C, 119Sn NMR spectroscopies, showing that ligands act as dianonic chelating agents. In solution phase, NMR data suggest that the bidentate chelation is attained by the O1 carboxylate and the vicinal O2 alkoxide atoms, which can be dynamically extended to a third binding site (O4) competing with O2. In Me2Sn(IV)-D-gluconate complex the occurrence of a self-association process leading to a dimeric species was also observed. Histopathological studies on different organs of Liza saliens showed that the dibutyltin(IV)-D-aldonate complexes, although preserving the defense immunity system, exhibit a specific toxicity on some target cells and organs. The toxicity of such complexes has been compared with respect to the effects of a previous study with tributyltin(IV) chloride solutions. Copyright © 2008 John Wiley & Sons, Ltd.

A novel and efficient method for preparing 99mTc-complexes of radiopharmaceuticals has been developed by reacting [99mTc]pertechnetate with a ligand in the presence of borohydride exchange resin (BER) as a reducing agent. The latter is stable over a wide range of pH (2–11) and thus can be used with biologically active compounds without the formation of insoluble 99mTcO2 or SnO2 colloids. Since the radiolabelled complexes are produced with high radiochemical purity and labelling efficiency under milder conditions than those required for the conventional reducing agents, the latter can be replaced. The method is expected to be applicable to the preparation of 99mTc-radiopharmaceuticals. Copyright © 2004 John Wiley & Sons, Ltd.

New saccharide polymers were synthesized via free radical polymerization. The saccharide compounds in copolymerisation reactions were 2,4,6-tri-O-acetyl-3-deoxy-D-erythro-hex-2-enono-1,5-lactone (1), (Ac-GEL 1) and 2,4,6-tri-O-benzoyl-3-deoxy-D-erythro-hex-2-enono-1,5-lactone (2), (Bz-GEL 2). These sugar monomers are easily obtained with high yield in a one step reaction from glucono-δ-lactone. They have a pyranoid structure containing an endocyclic double bond and they are electron acceptor compounds. Copolymerization reactions were carried out in solution an in substance. Copolymers with different sugar contents and low as well as high molecular weights were obtained. The structures and the compositions of the soluble saccharide polymers were established by elemental analysis, polarimetry, FTIR spectroscopy, 1 H an 13 C NMR spectroscopy. Some characteristic properties, e.g., molecular weight, optical rotation and copolymerization parameters are reported.

Novel poly(ethylene glycol) (PEG) derivatives having both carboxylic acid, und sugar side chains were synthesized. These polymers were used to coat DNA/ poly(ethyleneimine) complexes, and effectively protected them against albumin-induced aggregation. They presented carbohydrate moieties on the DNA complex surfaces as a cell-binding ligand, and the galactose-bearing polymer remarkably enhanced the poly(ethyleneimine)-mediated gene transfection on HepG2 cells.

In nature, 5,6-dimethyl-1-(α-D-ribofuranosyl)benzimidazole exists as a moiety of vitamin B12 (Ref 1). The furanosyl benzimidazole can be considered as Cnucleoside mimic. Due to its structural similarity to purine, benzimidazole is also an important chemical entity in pharmaceuticals 2 . In one approach, aldobenzimimdazoles are prepared by the condensation of aldonic acid or aldonic δ-lactones with o-phenylenediamine 3 . The condensation reactions are often conducted in strong acidic conditions at elevated temperature (e.g.135°C) 4 . The teritol-1-yl benzimidazoles can be further converted to furanosyl benzimidazoles by Lewis acid promoted dehydrative cyclization 5 . In another approach, aldoses are subjected to oxidative condensation with o-phenylenediamine to give aldobenzimidazoles in a direct manner 6 . This approach mitigates the laborious work in the prior preparation of aldonic acids from the corresponding aldoses 7 . For example, Moore and Link 4 have previously applied this approach to synthesize two monosaccharides benzimidazoles, D-gluco and Dgalactobenzimidazoles, in 24% and 50% yields from D-glucose and D-galactose, respectively, by heating with cupric acetate (2 equiv) at 53°C for 14 hr in aqueous acetic acid solution. Some saccharide bisSchiff bases and quinaxolines also form as side products under such reaction conditions 4-6 . However using catalytic amounts of CuSO4 or replacing the AcOH solvent with MeOH does not give any desired aldo-benzimidazoles 8 . Considering the acid-sesitive internal glycosidic bonds in disaccharides and higher saccharides, it is questionable that the corresponding aldo-benimidazoles can be obtained by the above mentioned reactions involving acidic conditions at high reaction temperature. In continuation of our study, the novel transformation of aldehyde and aldoses by use of amines and iodine 9-12 , we describe herein an improved protocol for the synthesis of various aldo-benzimidazoles by direct oxidative condensation of aldoses, including different mono-saccharides with substituted ophenylenediamine in the presence of iodine.

New styryl-type water-insoluble and methacryloyl-type water-soluble monomers, N-(p-vinylbenzyl)-1,2-O-isopropylidene-6-D-glucofuranuronamide and N-(2-methacryloylamino)ethyl-1,2-O-isopropylidene-6-D-glucofuranuronamide, were synthesized from the most common acidic saccharide, D-glucuronic acid. Their radical homopolymerizations and copolymerizations with styrene and acrylamide were tried under various conditions. The isopropylidene groups in the resulting polymers were removed in a mixture of trifluoroacetic acid and water (2/1 v/v) to give the corresponding polymers with many pendant D-glucopyranuronyl groups with reactive reducing groups. The pendant reducing ends may be useful as potential binding sites under a hydrophilic atmosphere. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3893–3901, 2001

The oxidation of D-glucitol and D-mannitol by CrVI yields the aldonic acid (and/or the aldonolactone) and CrIII as final products when an excess of alditol over CrVI is used. The redox reaction occurs through a CrVICrVCrIII path, the CrVICrV reduction being the slow redox step. The complete rate laws for the redox reactions are expressed by: a) −d[CrVI]/dt {kM2 H [H+]2+kMH [H+]}[mannitol][CrVI], where kM2 H (6.7±0.3)⋅10 M s−1 and kMH (9±2)⋅10 M s−1; b) −d[CrVI]/dt {kG2 H [H+]2+kGH [H+]}[glucitol][CrVI], where kG2 H (8.5±0.2)⋅10 M s−1 and kGH (1.8±0.1)⋅10 M s−1, at 33°. The slow redox steps are preceded by the formation of a CrVI oxy ester with λmax 371 nm, at pH 4.5. In acid medium, intermediate CrV reacts with the substrate faster than CrVI does. The EPR spectra show that five- and six-coordinate oxo-CrV intermediates are formed, with the alditol or the aldonic acid acting as bidentate ligands. Pentacoordinate oxo-CrV species are present at any [H+], whereas hexacoordinate ones are observed only at pH

Several filter aids were investigated in order to separate the hydrolyzed egg yolk suspension easily. λ-Carrageenan was found to be the most effective flocculant for the purpose. The addition of 1.67 g λ-carrageenan to 1 L of hydrolyzed egg yolk suspension was effective to get a clear supernatant. The ionic flocculation between the λ-carrageenan and the egg yolk lipoprotein was presumed. Using λ-carrageenan, N-acetylneuraminic acid containing in the hydrolyzed delipidated egg yolk was prepared. λ-Carrageenan did not adsorb to an anion exchange resin and could be separated completely from N-acetylneuraminic acid, when the filtrate treated with λ-carrageenan was applied on a column of the resin.

A new styrene derivative having an L-gulonic moiety, N-(p-vinylbenzyl)-6-L-gulonamide (VB-6-Glco, 3) was synthesized from L-gulono-1,4-lactone and p-vinylbenzylamine. The styrene derivative (3) was subjected to the radical homopolymerization and copolymerization with acrylamide and acrylic acid. The hydrolysis of p-nitrophenyl β-D-glucuronide with β-glucuronidase was scarcely inhibited in the presence of the glycopolymer prepared from 3 and acrylamide (P(VB-6-Glco-co-AAm), 4), whereas the glycopolymer prepared from 3 and acrylic acid (P(VB-6-Glco-co-AAK), 5) was found to suppress the enzyme activity strongly as well as a polystyrene derivative having pendant D-glucaric moieties (P(VB-6-GlcaH-co-AAm), 6). From the kinetic analysis of the hydrolysis, the glycopolymers 6 and 5 were postulated to inhibit the enzyme competitively and uncompetitively, respectively.

The dynamic wetting behaviour on a perfluorinated, low-energy solid has been investigated for a carbohydrate-modified phenylsiloxane surfactant. The surfactant concentration, the rate of interface generation and the [solid/liquid interface area] : [liquid/vapour interface area] ratio were varied systematically. Dynamic data for the liquid/vapour (γ Iv ) and solid/liquid (γ sl ) interfacial tension as well as their Lifshitz-van der Waals and donor-acceptor contributions were determined under strictly controlled conditions. Since γ sl reacts sensitively to variations of the surfactant concentration and the rate of interface generation, the covering of the liquid/nonpolar solid interface is assumed to be a spreading limiting factor. The corresponding γ lv values remain constant and close to those obtained under equilibrium conditions.

Branched siloxanyl-modified carbohydrate surfactants have been synthesized by coupling mono-, di- and poly-functional siloxanes to carbohydrate units either via a branched spacer or by attaching a separate modifying element to a straight-chained structure. Hydrophilic as well as extremely hydrophobic elements have been incorporated successfully. Siloxanyl-modified carbohydrates bearing a secondary amino function were alkylated in regioselective reactions by different epoxides ranging from glycidol- to siloxanyl-modified allyl glycidyl ether derivatives. Alternatively, carbohydrate-modified piperazinyl structures yielded cyclic subunits after alkylation. Structures bearing two identical hydrophilic groups are accessible by alkylation of carbohydrate-modified bisamides. The derivatives synthesized were characterized by means of GC, NMR and elemental analysis.

New siloxanyl-modified carbohydrate surfactants of the amide and glycoside type have been synthesized by coupling between defined as well as higher-molecular-weight siloxanes and carbohydrate structures via spacers of different lengths and hydrophilic power. Linear and branched monohydrogen di-, tri-, tetra- and penta-siloxanes and polyhydrogen siloxanes as well as mono- and di-saccharide lactone structures have been found to be good starting materials for the synthesis of amides, often in quantitative yield, whereas glycosides had to be prepared in low-yield multistep sequences including protection/deprotection steps. Selected strategies were applied to polysiloxanes yielding quantitatively a broad variety of carbohydrate-modified comb-like structures. The new substances were characterized by means of 13 C NMR spectroscopy, GC, capillary GC, GC-MS coupling and elemental analysis.

The novel influenza virus neuraminidase inhibitor GG167 (5-acetylamino-4-guanidino-2,6-anhydro-3,4,5-trideoxy-D-glycero-D-galacto-non-2-enoic acid) was labelled with 11 C for use in positron emission tomographic studies of drug deposition following intranasal or inhaled administration. [ 11 C]GG167 was obtained within a synthesis time of 50min via a two-step procedure, starting from [ 11 C]cyanogen bromide.

A procedure for characterization of sialic acid-like monosaccharides, i.e. 3-deoxy-2-ulosonic acids, by gas chromatography/mass spectrometry is described. The free monosaccharides were reduced with NaBH 4 and the resulting 3-deoxyaldonic acids were acetylated. Five-membered ring lactones were obtained as the major products. The keto-deoxy compounds N-acetylneuraminic acid, N-glycolylneuraminic acid, 3-deoxy-D-manno-2-octulosonic acid and 3-deoxy-D-glycero-D-galacto-2-nonulosonic acid were investigated. A detailed study of the electron impact ionization fragmentation pathways of the acetylated lactones were conducted using tandem mass spectrometry. The mass spectra allowed unambiguous structural identification of the acidic monosaccharides.

A series of new water-soluble photoinitiators (PIs) for UV curing of water-borne systems was synthesized by covalent bonding of carbohydrate residues such as D-glucose, sucrose, maltose, 1-amino-D-sorbitol and D-gluconicacid-δ-lactone to the commercially available PI 2-hydroxy-1-[4-(2-hydroxy-ethoxy)phenyl]-2-methylpropan-1-one (Darocur 2959) (1). In addition, new functional derivatives of 1 containing tosyl- or chloride residues as well as primary or secondary amino groups were prepared. Preliminary photocalorimetric tests of the activity demonstrated excellent efficiencies of the PIs in a commercial water-based acrylate formulation exceeding the photoactivity of the reference PI (1) substantially

Both enantiomers of endo-brevicomin (+)- and (−)-3a were synthesized from D-erythronolactone (1) and 2,3-O-isopropylidene-L-erythrose (2), respectively. In the course of the synthesis also the 7-vinyl analogues (+)- and (−)-3b of endo-brevicomin are available. The key step of the synthesis is the diastereoselective acetalization of the diols 1 and 10 with 4-(phenylsulfonyl)-2-butanone (4) and boron trifluoride-diethyl ether complex as a catalyst. The described procedure yields the key compounds 5a and ent-7b in good yields and with high diastereomeric purity.

A convenient one-pot procedure, simply involving air oxidation in strongly alkaline solution, is detailed for the high-yield conversion of bulk accessible D-glucosyl-α(16)-D-fructose (isomaltulose, 1) into the salt of the next lower aldonic acid, i.e. glucosyl-α(15)-D-arabinonate (4). Being only two steps away from sucrose, 4 is capable of providing a variety of disaccharide building blocks with potential industrial application profiles: open-chain esters, amides or alditols (8–12), or – via the respective 1,4-lactone 5 and suitable elimination reactions – various enantiopure 2-(5H)-furanones (14–17) with a preparatively useful (5S)-hydroxymethyl group, O-protected with an acid-labile glucosyl residue.

Monolithiated 1,7-dicarba-closo-dodecaborane(12) reacts with O-isopropylidene derivatives of D-erythrono-1,4-lactone (1), L-mannono-1,4-lactone (3) and with tetra-O-trimethylsilylated D-glucono-1,5-lactone (2) and D-gulono-1,4-lactone (4) to give the title compounds after deprotection. An X-ray structure analysis of the protected L-mannofuranose carborane derivative 9 reveals that the more stable anomer has the β-L configuration.

Furanoid and pyranoid glyconothio-O-lactones were prepared by photolysis of S-phenacyl thioglycosides or by thermolysis of S-glycosyl thiosulfinates, which gave better results than the thionation of glyconolactones with Lawesson's reagent. Thermolysis of the thiosulfinates obtained from the dimannofuranosyl disulfide 7 or the manofuranosyl methly disulfide 8 (Scheme 2) gave low yields of the thio-O-lactone 2. However, photolysis of the S-phenacyl thioglycoside 6 obtained by in situ alkylation of the thiolato anion derived from 5 led in 78–89% to 2. Similarly, the dithiocarbonate 10 was transformed, via11a, into the ribo-thio-O-lactone 12 (79%). Thermolysis of the peracetylated thiosulfinates 14 (Scheme 3) led to the intermediate thio-O-lactone 15, which underwent facile β-elimination of AcOH ( 16, 75%) during chromatography. The perbenzylated S-glucopyranosyl dithiocarbonate 18 (Scheme 4) was transformed either into the S-phenacyl thioglucoside 19 or into a mixture of the anomeric methyl disulfides 21a/b. Whereas the photolysis of 19 led in moderate yield to 2-deoxy-thio-O-lactone 20, oxidation of 21b and thermolysis of resulting thiosulfinates gave the thio-O-lactone 4 (79%), which was transformed into 20 (36%) upon photolysis. The pyranoid manno-thio-O-lactone 26 was prepared in the same way and in good yields from 22via the dithiocarbonate 24b and the disulfide 25. The ring conformations of the δ-thio-O-lactones, flattened 4C1 for 15 and 4 and B2,5 for 26, are similar to the ones of the O-analogous oxo-glyconolactones. The reaction of 2 (Scheme 5) with MeLi and then with MeI gave the thioglycoside 27 (29%) and the dimeric thio-O-lactone 29 (47%). The analogous treatment of 2 with lithium dimethylcuprate (LiCuMe2) and MeI led to a 4:1 mixture (47%) of 31 and 27. The structure of 2 was proven by an X-ray analysis, and the configuration at C(6) and C(5) of 29 was deduced from NOE experiments. Substitution of MeI by CD3I led to the CD3S analogues of 27, 29, and 31, i.e. 28, 30, and 32, respectively, evidencing carbophilic addition and ‘exo’-attack on 2 by MeLi and the enethiolato anion derived from 2. The preferred ‘endo’-attack of LiCuMe2 is rationalized by postulating a single-electron transfer and a diastereoselective pyramidalization of the intermediate radical anion.

A new approach towards simple aldonic acid derivatives starting from the corresponding aldoses via the 2-acetamido-2-deoxy formazans resulted in the synthesis of 2-acetamido-2-deoxy- d -galactono-1,4-lactone (8), and its 6-deoxy (11) and 6-azido-6-deoxy (14) analogues on treatment with trifluoroacetic acid. The five-membered ring structure of the lactones and that of the intermediate lactone phenylhydrazone (7) was proved by 1H and 13C NMR studies, including deuterium-induced differential isotope shift (DIS) measurements. With sodium borohydride, lactones 8 and 11 were converted into 2-acetamido-2-deoxy- d -galactitol (15) and its 6-deoxy analogue (17), respectively.

6-Deoxy-6- C -sulfo- d -glucopyranose (sulfoquinovose) has been prepared and characterised as its brucinium and potassium salts. The bis-cyclohexylammonium salt of its aldonic acid, 6-deoxy-6- C -sulfo- d -gluconic acid, has also been obtained. Their oxidation by sodium periodate gives 2-sulfoacetaldehyde.

Here we present a one-pot procedure for the synthesis of a library of carbohydrate compounds belonging to four classes of glycosidase inhibitors: glycosides, aldonic acid lactams, aldonic acid lactones and dideoxy-iminoalditols. The complex mixture was separated into individual components that were screened for activity against α- and β-glucosidases. Among these were two 2- O -methyl glycosides that reduced the rate of the enzymatically-catalyzed hydrolysis of the p -nitrophenyl glucosides used in the assay. Relative inhibition indices normalized to the inhibition observed with deoxynojirimycin under similar conditions were determined. This methodology provides a straightforward, general and time-efficient way to synthesize, test and analyze an extensive number of glycosidase inhibitor candidates from several carbohydrate compound classes in one scheme. The direct reference to deoxynojirimycin gives an immediate indication of the concentration range in which a significant inhibitory activity can be obtained.

From 4-O-unsubstituted glucose derivatives 1a, b the 4-hydroxymethyl-substituted glucose derivatives 9a, b were obtained via oxidation to the ketone, Wittig reaction with methylenetriphenylphosphorane, borane addition, and subsequent oxidation to yield the diastereomeric galactose-derived compounds 5a, b; the required inversion of configuration at C-4 was accomplished through oxidation to the formyl derivatives, base-catalyzed isomerisation, and then reduction. Transformation of hydroxymethyl derivatives 9a, b into the iodo derivatives 11a, b and reaction with n-butyllithium generated the C-lithiated species 11aA, bA which furnished with O-benzyl-protected gluconolactone 12 the ketose derivatives 13a, b. Treatment with Et2O–BF3 afforded under concomitant 6-O-debenzylation the spiroketals 15a, b. Hydrogenolytic O-debenzylation and subsequent O-acetylation led to compounds 16a and 16b, respectively. The anomeric ketoside configuration was derived from NOE experiments.

Synthesis of C-Glycosides of N-Acetylneuraminic Acid and Other Derivatives Reaction of the β-pyranosyl chloride 1 of N-acetylneuraminic acid with allyl(tributyl)stannane under radical-induced conditions affords a mixture of the allyl C-glycosides 2/3. After deprotection, the pure allyl α-C-glycoside 5 and the analogous β isomer 7 can be isolated. The allyl C-glycosides 2 and 3 are converted into the corresponding epoxypropyl C-glycosides 9 and 11 by epoxidation of the allylic group. Further modified allyl C-glycosides are prepared from the C-3-hydroxylated N-acetylneuraminic acid, which are available as pure α- and β-C-glycosides 19 and 21 after deprotection. At C-3 modified compounds are also synthesized which have allyl and azido residues at C-3. All compounds are interesting as potential inhibitors of sialidases, CMP sialate syntheses, and viral infection.

The peracetylated methyl ester 1 of N-acetylneuraminic acid was transformed into the oxazoline derivative 2, which was hydrogenated with Pd/C/H2 to give the 4-deoxy-Neu5Ac2en derivative 3. Acid cleavage of the oxazoline 2 by trifluoroacetic acid (THF) gave the 4-epi-Neu5Ac2en derivative 4a, which was saponified to the known 4-epi-Neu5Ac2en 4b. Treatment of 4a with triphenylphosphane/diethylazodicarboxylate (DEAD)/HN3 in toluene gave the 4-azido-4-deoxy-Neu5Ac2en derivative 5a as well as the 4-epi-azido-4-deoxy-Neu5Ac2en derivative 6a. Both epimers could be saponified yielding the free dehydrosialic acid derivatives 5b and 6b. Furthermore, 4-formamido-4-deoxy-Neu5Ac2en 7b was prepared via the derivative 7a, which was formed from 5a by reaction with triphenylphosphane/formyl acetate. In addition, the free dehydrosialic acid derivatives 5b and 6b were transformed into the stable PN ylides 8 and 10, but only 8 could be hydrolyzed to the triethylammonium salt of 4-amino-4-deoxy-Neu5Ac2en 9a, which was converted into the zwitter ionic compound 9b. Finally 4-acetamido-4-deoxy-Neu5Ac2en 11e was prepared from 4-acetamido-4-deoxy-N-acetylneuraminic acid 10 via the derivatives 11a and 11b by well-known methods. The compounds 4b, 5b, 6b, 7b, 9b, and 11c were investigated as inhibitors of Vibrio cholerae sialidase, and their Ki values were determined.

The synthesis of 5-acetamido-2,6-anhydro-3,5-dideoxy-D- erythro-L-manno-nonic acid (3b, 7,8-epi2-2-d-2-HeqNeu5Ac) and sodium 5-acetamido-2,6-anhydro-3,5-dideoxy-L-threo-L-manno-nonate (6b, 8-epi-2-d-2-Heq-Neu5Ac) could be realized by transformation of 5-acetamido-3,5-dideoxy-L-glycero-L-altro-2-nonulopyranosonic acid (2a, 7,8-bis-epi-Neu5Ac) and 5-acetamido-3,5-dideoxy-3-L-glycero-D-galacto-2-nonulosonic acid (5a, 8-epi-Neu5Ac) into the corresponding peracetylated 2-chloro derivatives and subsequent catalytic hydrogenation. As this procedure could not be applied to the synthesis of the 7-epi, 7-deoxy and 8-deoxy derivatives a new strategy, which started with the methyl 5-acetamido-2,6-anhydro-3,5-dideoxy-D-erythro-L-manno-nonoate (1e), was designed. For this purpose, a gram-scale preparation of 1e was developed. Transformation of protecting groups and radical reduction of selectively introduced tolylthiocarbonate groups led to the corresponding 5-acetamido-2,6-anhydro-3,5,7-trideoxy-D-glycero-L-manno-nonoic acid (12b, 2,7-d2-2Heq-Neu5Ac) and sodium 5-acetamido-2,6-anhydro-3,5,8-trideoxy-D-glycero-L-manno-nonate (11b, 2,8-d2-2Heq-Neu5Ac). An oxidation — reduction sequence yielded 5-acetamido-2,6-anhydro-3,5-dideoxy-D-threo-L-manno-nonoic acid (9c, 2d-2Heq-7-epi-Neu5Ac). Also the sialic acid analog 6b could be prepared according to this newly designed strategy.

Starting from D-ribonolactone, the cyclopentylidene-protected dihydroxy ester 12 was prepared in five steps. Reaction of its enolate 13 with benzyloxymethyl iodide gave the esters 15 and 16 with modest selectivity. Each of these was converted into the desired mycinolide building block 32 in seven and six steps, respectively.

A nonclassical, totally stereoselective synthesis of orthogonally protected 1,3-disaccharides is reported. Enantiomerically pure beta-keto-delta-lactones, efficiently obtained from glucal and galactal, are transformed into electron-poor heterodienes and chemo-, regio-, and stereoselectively cycloadded to glycals as electron-rich dienophiles, to directly afford 2-thiodisaccharides. The reductive desulfurization of the latter smoothly gave the corresponding 2,2'-dideoxydisaccharides.

3,4-Di-O-benzyl-2,6-dideoxy-L-arabino-hexono-1,5-lactone (1b) was synthesized in three steps by starting from di-O-acetyl-L-rhamnal (6). Sequential treatment of 1b or 3,4,6-tri-O-benzyl-2-deoxy-D-arabino-hexono-1,5-lactone (1a) with triethyloxonium tetrafluoroborate and sodium ethanolate produced the diethyl ortholactones 2a and b. Acid-catalyzed reaction of 2a or b with 1,2-ethanediol (5a) or (1S,2S)-1,2-cyclohexanediol (5b) gave the spiro ortholactones 3a, b, and 4a, b.

Durch Umsetzung des aus zwei Glucosamin-Einheiten bestehenden Disaccharides 9 mit dem Pyranosylbromid der 3-Desoxy-D-manno-2-octulosonsaure (KDO) 11 sind die KDO-haltigen Trisaccharide 12 und 14 zu erhalten, von denen das α-glycosidisch verknupfte Produkt 12 sehr stark uberwiegt. Durch eine Entblockierungssequenz ist aus 12 das freie Trisaccharid α-KDO-(23)-β-D-GlcNAc-(16)-D-GlcNAc 18 zu gewinne. Die Zuordnung zur α-glycosidischen Verknupfung des KDO-Teiles in 12 erfolgte durch Uberfuhrung von 19 in das Lacton 20. Building Units of Oligosaccharides, LIII. - Synthesis of Trisaccharides Containing 3-Deoxy-D-manno-2-octulosonic Acid (KDO) The disaccharide 9 consisting of two glucosamine units reacts with the pyranosyl bromide of 3-deoxy-D-manno-2-octulosonic acid (KDO) 11 to give the KDO-containing trisaccharides 12 and 14 of which the α-glycosidically linked isomer 12 is the most preponderant product. In a series of deblocking steps the free trisaccharide α-KDO-(23)-β-D-GlcNAc-(16)-D-GlcNAc 18 could be obtained from 12. The assignment to the α-glycosidic linkage of the KDO unit in 12 has been established by converting 19 into the lactone 20.

D-Altronate hydratase and D-mannonate hydratase belong to a class of Fe2+-requiring enzymes, but the function of iron in these enzymes is largely unknown. Methods are described for the convenient preparation of both these hydratases from Escherichia coli and studies related to metal activation are presented. The enzymes are inactive in the absence of a bivalent metal and a reducing agent such as dithiothreitol. Fe2+ at low concentrations activates the enzymes efficiently, but inhibits them over 2 mM. Furthermore Mn2+ is also capable of activating aldonic acid hydratases and appears to be a constituent of the enzyme active center. A marked synergistic activation is observed in the presence of both ions, raising the possibility that the enzyme has two binding sites for ions. Upon activation, the two aldonic acid hydratases incorporate a single Fe atom and contain no Fe-S core, in contrast to other characterized Fe-hydratases, such as aconitase or maleic acid hydratase. The incorporated iron is losely bound (with Kd about 4.5 mM and 20 mM for mannonate and altronate hydratase, respectively) and can be readily removed with EDTA. The enzymes exhibit no requirement for sulphide ions and are insensitive to thiol reagents. A first-order inhibition is observed with iron chelators and can be removed by competition with excess metal ions. No change in the absorption spectra is observed upon oxidation-reduction or activation with metals. The activated enzymes exhibit no electron paramagnetic (EPR) spectrum under anaerobic conditions; in the presence of oxygen, an intense EPR spectrum develops in Fe2+-activated samples with signal at g = 1.98, which upon reaction of the enzyme with the substrate moves into a species with signals at g = 4.15 and g = 9.07, with EPR parameters very similar to those of oxidized rubredoxins.

The synthesis of the 6-amino-6-deoxysialic-acid analogues 4, 5, and 6, is described. Mitsunobu reaction of the 1-C-nitroglycal 8, (PPh3, HCOOH, DEAD) gave the formiate 10 with inversion of configuration at C(3) (Scheme 2). Treatment of 10 with aq. NH3 and subsequent protection of the amino function gave the imines 14 and 15 (Scheme 3), which were transformed into the triflates 17. Substitution by azide, deprotection, and N-acetylation gave the anormeric 2-acetamido-3-azido-1-deoxy-1-nitro-D-mannoses 16 and the enol ether 18. Chain elongation of the nitro azides 16 followed by hydroylsis gave the nonulosonates 20/22, which upon reduction yielded the diols 23 and 24, respectively (Scheme 4). The diol 23 was transformed into the sialic-acid analogues 5, 6, and 32 by ozonolysis, transfer hydrogenation, hydorgenolysis, and deprotection (Scheme 5), and the diol 24 into 4 by a similar reaction sequence. The sialic-acid analogues 4 and 6 inhibit bacterial and viral sialidases competitively. The inbibitor constants for this enzyme from Vibrio cholerae are 0.12 mm for 4 and 0.19 mm for 6, respectively. The activity of fowl plague virus sialidase was reduced by 17% and 36% under the influence of 4 and 6, respectively, at a concentration of 0.1 mM. Compound 5 was inactive.

A new and easy general methodology has been developed to prepare γ-alkyl-α,β-butenolides or γ-alkylbutyrolactones in four and five steps, respectively, from D-ribonolactone as a common chiral starting material. Some of these products have pheromonal activity in insects and are also used as fruit fragrances. A study on several derivatives of D-ribonolactone and 2-deoxy-D-ribonolactone has been carried out in order to explore alternative routes for these syntheses.

Note: Univ lausanne,chim sect,2 rue barre,ch-1005 lausanne,switzerland. Reference LGSA-ARTICLE-1989-007doi:10.1002/hlca.19890720819 Record created on 2005-11-09, modified on 2017-05-12

Steroselective Alkylation at C(α) of Serine, Clyceric Acid, Threonine, and Tartaric Acid Involving Heterocyclic Enolates with Evocyelic Double Bonds The chiral, non-racemic title acids are converted to methyl dioxolane-(cf.13), oxazoline-(4) and oxazolidinecarboxylates (cf.9). Deprotonation by Li(i-Pr) 2N at dry-ice temperature gives solutions of the lithium enolates A–D With exocyclic enolate double bonds. These are stable crough with respect to β-elimination (Scheme 1) to be alkylated with or without cosolvents such as HMPA or DMPU The products are formed in good to excellent yields and, with the exception of the tartrate-derived acetonlde (see Scheme 2), with diastereoselectivities above 90%. While the tartrate-and threonine-derived enolates (A and B, resp.) are chiral due to the second stereogenic center of the precursors, the serine- and glyceric-acid-derived enolates (Aand B, resp.) are chiral due to the second sterogenic center of the precursors, the serine-nd glyceric-acid-derived enolates are non-racemic due to a tert butyl-substituted (pivalaldehyde-derived) acetal center (C and D, resp.). The products of alkylation can be hydrolyzed to give α-branched tartaric acid (Scheme 2), allothreonine (Scheme 3), serine (Scheme 4), and glyceric-acid derivatives (Scheme 5) with quaternary stereogenic centers. The configurations of the products are determined by NOE-NMR measurements and by chemical correlation. These show that the dioxolane-derived enolates A and D are alkylated preferentially from that face of the ring which is already substituted (‘syn’-attack), while the dihydrooxazol-and oxazolidine-derived enolates B and C are alkylated from the opposite face (‘anti’-attack). The ‘syn’-attack is postulated to arise from strong folding of the heterocyclic ring due to electronic repulsion between the enolate π-system and non-bonding electron pairs on the heteroatoms (see Scheme 6).

Aus β-Chlormilchsaureester werden α-tert-Butoxyacrylsaure (4b) und die Amide 4c – 4f hergestellt. Mit sec-Butyllithium als Base konnen daraus direkt und in hoher Ausbeute die dilithiierten Spezies 4b-A – 4f-A erzeugt werden. Durch Reaktion von 4c-A – 4e-A mit 2,3:4,5-Di-O-isopropyliden-D-arabinose (11) als Elektrophil werden bevorzugt die D-manno-2-octulosonsaure-Derivate 12c-m – 12e-m gebildet. Aus 12c-m wird dann in drei einfachen und in hoher Ausbeute verlaufenden Stufen (Ringschlus zum Butenolid, Saure-katalysierte Schutzgruppenabspaltung und Uberfuhrung ins Pyranosid) KDO erhalten. Aus der als Nebenprodukt entstandenen D-gluco-Verbindung 12c-g wird entsprechend D-gluco-KDO synthetisiert. Functionally Substituted Vinyl Carbanions, 351). - Short Synthesis of 3-Deoxy-D-manno-2-octulosonic Acid (KDO) α-tert-Butoxyacrylic acid (4b) and the amides 4c – 4f are prepared from β-chlorolactate. sec-Butyllithium as a base generated directly the dilithiated species 4b-A – 4e-A in high yields. Reaction of 4c-A – 4e-A with 2,3:4,5-di-O-isopropylidene-D-arabinose (11) as an electrophile gives preferably the D-manno-2-octulosonate derivatives 12c-m – 12e-m. Compound 12c-m is transformed in three convenient, high-yielding steps (ring closure to the butenolide, acid-catalyzed deprotection, and pyranoside formation) into KDO. Correspondingly, D-gluco-KDO is obtained from the D-gluco-configuration byproduct 12c-g.

Mit dem Ziel, neue Anwendungsgebiete fur Starke zu finden, untersuchten wir verschiedene Wege, Oligo- und Polysaccharide mit synthetischen Produkten, insbesondere Polymeren zu verknupfen. Als ein relativ einfaches und in Bezug auf die Partner vielfach variierbares Verfahren erweist sich die Kopplung uber Amidbindung. Ausgehend von Amylose, setzt sich der Syntheseweg aus folgenden Schritten zusammen: 1. Herstellung von Maltooligomeren definierter Lange; 2. Einfuhrung von Aldonsaurelacton-Endgruppen; 3. Addition der Lactone an Trager mit Aminogruppen; 4. Enzymatische Verlangerung der gebundenen Oligosaccharide zu beliebig langen Amyloseketten. Verfahren, die in groserem praparativen Masstab anwendbar sind, werden beschrieben und am Beispiel der aliphatischen Amine als Trager angewendet. Preparative Methods for the Preparation of Higher Maltooligomers and their Coupling with Aliphatic Diamines In order to find new applications for starch we studied different ways of linking oligo- and polysaccharides to synthetic products, especially polymers. Coupling by means of amide linkages proves to be a convenient method which allows manifold variation of the components. Starting from amylose the synthesis consists of the following steps: 1. Preparation of maltooligomers of definite lengths; 2. Introduction of aldonic acid lactone endgroups; 3. Addition of the lactones to carriers containing amino groups; 4. Enzymatic elongation of the oligosaccharide grafts to amylose chains of any predetermined length. Procedures applicable for larger scale preparation are described and illustrated with aliphatic diamines as carriers.

The titanium derivative 3 and the lithium derivative 2 of the bislactim ether 1 of cyclo(-L-Val-Gly-) react with (R)- and (S)-glyceraldehyde (cyclohexylidene-protected, 9) and with (S)-lactaldehyde (Mem-protected, 10) to give virtually only one diastereomer. The extent of asymmetric induction is higher for (S)-9 and 10 than for (R)-9. The results can be rationalized on the basis of pericyclic reactions with six-membered chair-like transition states. – On acid hydrolysis (subsequent to O-acetylation) the aldol-type addtion products 11, 12, and 13 are cleaved to give the amino acid methyl esters 14, 15, and 16 with multiple stereocenters. 15 and 16 are enantiomerically and diastereomerically pure. Asymmetrische Synthesen uber heterocyclische Zwischenstufen, XXVII. – Umsetzungen metallierter Bislactimether von cyclo(-L-Val-Gly-) mit (R)- und (S)-Glycerinaldehyd und mit (S)-Lactaldehyd Die Titan- und Lithiumderivate 3 und 2 des Bislactimethers 1 von cyclo(-L-Val-Gly-) reagieren mit (R)- und (S)-Glycerinaldehyd (cyclohexylidengeschutzt, 9) und mit (S)-Lactaldehyd (Mem-geschutzt, 10) stereoselektiv, wobei praktisch nur ein Diastereomeres entsteht. Das Ausmas der Induktion ist mit den (S)-Aldehyden hoher als mit dem (R)-Aldehyd. Die Ergebnisse lassen sich als pericyclische Reaktion mit sechsgliedrigen Sesselubergangszustanden deuten. — Die Aldol-Addukte 11, 12 und 13 sind (nach O-Acetylierung) sauer hydrolysierbar, wobei man die Aminosaure-methylester 14, 15 und 16 mit mehreren Stereozentren erhalt. 15 und 16 sind enantiomeren- und diastereomerenrein.

Das Pyranosylbromid 2 der 3-Desoxy-D-manno-2-octulosonsaure (KDO) last sich am gunstigsten mit dem Benzyl-2-benzyloxycarbonylamino-2-desoxy-4,6-O-ethyliden-α-D-glucopyranosid (7) zu (23)-glycosidisch verknupften Disacchariden aus KDO und D-Glucosamin umsetzen. Je nach Art des Losungsmittels wird nur das α-D-glycosidisch verknupfte Produkt 10a oder ein Gemisch der Anomeren erhalten. Quecksilbersalze dienen als Katalysatoren. Nach Trennung der Anomeren und Entblockierung wurden die beiden Disaccharide α-KDO-(23)-D-GlcNAc 21 und α-KDO-(23)-D-GlcNAc 26 dargestellt. Die Zuordnung der Anomerenkonfiguration erfolgte durch NOE-Experimente und durch Uberfuhrung in das Lacton 31. Building Units of Oligosaccharides, LII. - Synthesis of Disaccharides Containing 3-Deoxy-D-manno-2-octulosonic Acid (KDO) and D-Glucosamine The pyranosyl bromide 2 of 3-deoxy-D-manno-2-octulosonic acid (KDO) can be coupled favourably with benzyl 2-benzyloxycarbonylamino-2-deoxy-4,6-O-ethyliden-α-D-glucopyranoside (7) which yields the (23)-glycosidically linked disaccharide containing KDO and D-glucosamine. Using mercury salts as catalysts it depends on the kind of solvent whether only the α-D-glycosidically bound product 10a or a mixture of the anomers will be obtained. After separation of the anomers and deblocking, the two disaccharides α-KDO-(13)-D-GlcNAc 21 and β-KDO-(23)-D-GlcNAc 26 have been prepared. The assignment of the anomeric configuration could be accomplished by NOE experiments and by conversion into the lactone 31.

Sugar solutions at a concentration of 0.10% were subjected to low-level ozonation, in order to oxidize the solute directly or indirectly to the corresponding aldonic acid. Charcoal adsorption of the monosaccharides was more efficient after ozonation. Adsorption of the disaccharides was, by far, less efficient after ozonation. The chemical oxygen demand of a standard gluconic acid solution was reduced to 10% of its original concentration by charcoal alone.

The reaction of protected aldonic acid lactones with ethyl isocyanoacetate and base in aprotic medium gives either α(formylamino)acrylic ester derivatives or acyclic sugar oxazole derivatives, where base-catalysed elimination reactions can be suppressed.

1. A novel synthesis of 3,6-dideoxy-L-arabino-hexose from L-rhamnose has been performed. 2. The γ-lactones of 3,6-dideoxy-L-arabino- and L-ribo-hexonic acids have been prepared and the13C NMR spectra of aldonic acid γ-lactones have been analyzed.