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Stereoselective syntheses of new pyranopyrans that are related to the natural product diplopyrone, which is a phytotoxin implicated in cork oak decline, have been achieved from carbohydrate starting materials in two approaches that are based on

(2S,4aR,8aR)-6-Oxo-2,4a,6,8a-tetra­hydro­pyrano[3,2-b]pyran-2-carboxamide, a potentially effective anti­bacterial agent, was prepared by a chemoselective hydration of the corresponding nitrile using a heterogeneous catalytic method based on copper(II) supported on mol­ecular sieves, in the presence of acetaldoxime. It belongs to a new class of pyran­opyrans that possess anti­bacterial and phytotoxic activity., The pyran­opyran amide (2S,4aR,8aR)-6-oxo-2,4a,6,8a-tetra­hydro­pyrano[3,2-b]pyran-2-carboxamide, C9H9NO4, 3, was prepared by a chemoselective hydration of the corresponding nitrile, 2, using a heterogeneous catalytic method based on copper(II) supported on mol­ecular sieves, in the presence of acetaldoxime. Compound 3 belongs to a new class of pyran­opyrans that possess anti­bacterial and phytotoxic activity. Crystallographic analysis of 3 shows a bent structure for the cis-fused bicyclic pyran­opyran, similar to nitrile 2. Evidence of an intra­molecular hydrogen bond involving the amide group and ring oxygen was not observed; however, two separate inter­molecular hydrogen-bonding inter­actions were observed between the amide hydrogen atoms and adjacent carbonyl oxygen atoms along the b- and a-axis directions. The latter inter­action may also be supported by an inter­molecular C—H⋯O hydrogen bond. The lattice is filled out by close-packed layers of this hydrogen-bonded network along the c-axis direction, related from one to the next by a 21 screw axis.

The phytotoxin diplopyrone is considered to be the main phytotoxin in a fungus that is responsible for cork oak decline. A carbohydrate-based synthesis of the enantiomer of the structure proposed for diplopyrone has been developed from a commercially available derivative of d-galactose. Key steps in the synthesis are a highly stereoselective pyranose chain-extension based on methyltitanium, preparation of a vinyl glycoside via Isobe C-alkynylation-rearrangement/reduction, and RCM-based pyranopyran construction. Crystallographic and NMR analysis confirms an earlier report that the structure originally proposed for diplopyrone may require revision. Structural analogues were prepared for biological evaluation, the most promising being a pyranopyran nitrile synthesized from tri- O-acetyl-d-galactal by Ferrier cyanoglycosidation, Wittig chain extension, and lactonization. Biological assays revealed potent antibacterial activity for the nitrile analogue against common bacterial pathogens Edwardsiella ictaluri and Flavobacterium columnare that cause enteric septicemia (ESC) and columnaris disease, respectively, in catfish. The IC50 value of 0.002 against E. ictaluri indicates approximately 100 times greater potency than the antibiotic florfenicol used commercially for this disease. Phytotoxic activity for all three target compounds against duckweed was also observed. The antibiotic and phytotoxic activities of the new pyranopyrans synthesized in this study demonstrate the potential of such compounds as antibiotics and herbicides.

The glycopyranosyl cyanide 4,6-di-O-acetyl-2,3-dideoxy-α-D-threo-hexopyranosyl cyanide has been synthesized from tri-O-acetyl-D-galactal by reaction with trimethylsilyl cyanide in the presence of boron trifluoride diethyl etherate followed by catalytic hydrogenation. The synthesis provides the α-anomer stereoselectively, the structure of which was assigned based on 2D NMR techniques and x-ray crystallography.

The synthesis of 4-amino-4-deoxy carbohydrates that occur in antibiotics and in bacterial glycans is described. The focus of the coverage is on literature published since 2000; however, earlier work is included in some cases for the purposes of historical context and to highlight methods development in this active area of research. Syntheses based on both carbohydrate and noncarbohydrate starting materials serve to illustrate the variety of methods for the introduction of nitrogen functionality on the pyranose scaffold, as well as methods for chain extension using asymmetric and catalytic methods.

The protected glycoside of 2-amino-2-deoxyglucose (glucosamine), namely allyl 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-D-glucopyranoside, C23H25NO10, was synthesized from the glycosyl bromide. Crystallographic analysis confirmed the β-anomeric configuration and showed an approximately orthogonal orientation of the phthalimido group with respect to the pyranose ring. The absolute configuration of the molecule was known from the synthetic route and assigned accordingly.

Methods for the synthesis of cyclopropyl glycosides and their use as glycosyl donors are described. Cyclopropyl glycosides containing different substituents were prepared by cyclopropanation of the corresponding vinyl glycosides, or by glycosidation of cyclopropyl alcohols that are synthesized by the Kulinkovich reaction. 1-Methyl- and 1-phenyl-substituted cyclopropyl glycosides undergo coupling to Fmoc-protected serine and threonine and to partially protected monosaccharides in the presence of TMS triflate to give glycosidated products.

Three types of as prepared and treated graphite nanofibers (GNFs) were used as catalysts in the decomposition of isopropanol to propene and acetone in the presence of oxygen to evaluate the surface chemistry of the fibers. As prepared herringbone fibers were found to produce higher selectivity for propene compared to the as prepared platelet and ribbon fibers at all temperatures explored. Herringbone fibers that had undergone oxidative treatment with nitric acid, phosphoric acid, ruthenium tetroxide or potassium permanganate were also evaluated at a 290 °C. Effects of oxidation treatments on fiber structure were evaluated using a host of analytical techniques including BET, SEM/EDS, TGA, XPS, and fluorescence labeling of surface species. Selectivity for acetone dehydrogenation product or propene dehydration product could be achieved by the appropriate surface treatment. Nitric acid was the mildest treatment and the treated fibers showed minimal changes. (Potassium permanganate was a harsh treatment that almost completely degraded fiber structure, creating amorphous carbon.) Phosphoric acid treated fibers were found to produce very high conversions and almost pure selectivity for propene. Ruthenium tetroxide did not appear to have a large affect on fiber morphology; however, selectivity for acetone was much higher when GNFs were treated with ruthenium tetroxide.

The ability to quantify functional groups on graphitic carbon nanofiber (GCNF) surfaces and to covalently attach ligands chemoselectively will aid in the development of functionalized GCNFs and potentially other carbon nanomaterials for applications in nanotechnology. Herein, we report the identification and quantification of functional groups on the surface of GCNFs using fluorescence labeling of surface species (FLOSS). Using reactions that are selective for specific functional groups and fluorescent dyes containing the dansyl group, surface aldehyde/ketone, carboxyl, and hydroxyl groups were identified and quantified in their total and relative amounts by FLOSS. Oxygen-containing functionality that was detected by FLOSS on nitric acid-oxidized GCNFs totaled approximately 2.5% of surface carbon, present as 0.9% aldehyde/ketone, 1.2% carboxyl groups on average, and 0.4% hydroxyl groups. The amounts of oxygen-containing functional groups on as-produced and demineralized GCNFs were much lower, amounting to no more than 0.05% of aldehyde/ketone groups on demineralized GCNFs and 0.3% of these groups on as-produced fibers. The FLOSS method has revealed information about the fiber surface that is not accessible by other methods, while also providing insight into the chemical reactivities of functional groups that can be used as sites for the attachment of ligands to give covalently functionalized materials.

The addition of benzenesulfinic acid to glycals was investigated under various conditions, and optimized yields of the glycosyl phenylsulfone products were obtained in the presence of tin tetrachloride as a catalyst. Double bond shift (Ferrier rearrangement) occurred in all cases except amicetal, which lacks a substituent at the allylic carbon. Glycosylation of benzenesulfinic acid with 1,2-dibromides was carried out using silver triflate as the promoter, and gave sulfinate esters as products by reaction at oxygen rather than at sulfur. The sulfinate esters were obtained as mixtures of stereoisomers at the stereogenic sulfur atom. Trapping of the sulfinates with carboxylate nucleophiles was observed during attempted oxidation with MCPBA.

A new method for the synthesis of vinyl glycosides and carbohydrate vinyl ethers is described. Mixed acetal glycosides and other types of carbohydrate mixed acetals are treated with TMS-triflate and an amine base, conditions developed by Gassman for the synthesis of enol ethers from acetals. The elimination proceeds regioselectively in most cases but also gives silyl ethers as side products in others. The hetero-Diels–Alder reactions of carbohydrate 3- O - and 6- O -vinyl ethers with ethyl ( E )-ethoxymethylenepyruvate were carried out as part of a model study for the synthesis of deoxygenated disaccharides of antibiotics.

The disaccharide portion of the anthracycline antibiotic polyketomycin consists of the trideoxy sugar d -amicetose attached to the methyl-branched sugar l -axenose. The polyketomycin disaccharide was synthesized from methyl 2,3,6-trideoxy-α- d - erythro -hexopyranoside (methyl α- d -amicetoside) and phenyl 3,4-di- O -benzyl-2,6-dideoxy-3- C -methyl-1-thio-α,β- l - xylo -hexopyranoside. The key coupling step was carried out by N -bromosuccinimide activation of the thioglycoside and gave the desired α (1→4) linked disaccharide exclusively in 71% yield, which was debenzylated by sodium and liquid ammonia.

Lemonose is a component of the antibiotic lemonomycin and other antibiotics and natural products. Three routes to the synthesis of the title compound, a protected, desmethyl derivative of lemonose, from l-rhamnose or its glycal, were investigated based on electrophilic cyclization, epoxidation-ring opening, and deoxygenation of an intermediate that was used in the synthesis of the amino sugar callipeltose. The deoxygenation route was successful and it provided the title compound, which was then converted to a phenyl thioglycoside.

Surface functionalization of nanomaterials is an area of current investigation that supports the development of new biomaterials for applications in biology and medicine. Herein we describe the synthesis, characterization, and antibacterial properties of the first examples of antibiotic-labeled graphitic carbon nanofibers (GCNFs) covalently functionalized with aminoglycoside and quinolone antibiotics. Ruthenium tetroxide oxidation of herringbone GCNFs gave higher amounts of surface carboxyl groups than previous methods. These carboxyl groups served as sites of attachment for antibiotics by acyl substitution. Bioassay of these novel, functionalized GCNFs using serial dilution and optical density methods demonstrated that antibiotic-labeled GCNFs possess significant antibacterial activity againstPseudomonas aeruginosa. The activity we observe for aminoglycoside-functionalized GCNFs suggests a membranolytic mechanism of action.

Vinyl D-glucopyranosides are useful intermediates in a wide variety of applications in synthetic carbohydrate chemistry. They have been utilized as chiral auxiliaries in the inverse-electron-demand...

A new synthesis of the methyl-branched sugar axenose is described. Axenose is found in the antibiotics axenomycin, dutomycin, and polyketomycin. The synthesis is based on additions of organometallic reagents to pentodialdo-1,4-furanosides and allows the preparation of derivatives of methyl α- l -axenoside which are protected at the tertiary C-3 hydroxyl group. Conversion to thioglycoside derivatives for use in oligosaccharide synthesis was carried out directly from the methyl glycoside by treatment with phenylthiotrimethylsilane and trimethylsilyl trifluoromethanesulfonate.

The synthesis of callipeltose, a novel amino sugar with the proposed structure, 4-amino-4,6-dideoxy-2, O -3- C -dimethyl- l -talopyranosyl-3,4-urethane, from l -rhamnose is described. Oxime reduction, carbamate cyclization and selective methylation are key steps. The synthesis supports the assignment of the relative stereochemistry of callipeltose.

Three methods for the synthesis of the deoxy sugar amicetose (2,3,6-trideoxy- d - erythro -hexopyranoside) are described. All three utilize the known dihydropyran 2-isobutoxy-6-methyl-2,3-dihydro-4 H -pyran as an intermediate. Asymmetric hydroboration of the dihydropyran with IpcBH 2 gave enantiomerically enriched isobutyl α and β-amicetosides. Hydroboration with borane–tetrahydrofuran followed by derivatization of the major product (β-anomer) with R -(−)-1-(1-naphthyl)ethylisocyanate gave diastereomeric carbamates which were separated and converted to isobutyl β- d and β- l -amicetosides having high optical purity. Racemic isobutyl β-amicetosides were also resolved by enzymatic transesterification using lipase and an acyl transfer reagent. Porcine pancreatic lipase and lipases from Candida rugosa and Pseudomonas sp. were evaluated in the presence of either vinyl acetate, vinyl butyrate, or trifluoroethyl butyrate as acylating agents. A GC-based method for determining enantiomeric purity of amicetose derivatives was developed.

Derivatives of the branched amino sugar methyl 3-amino-2,3,6-trideoxy-3-C-methyl-α-L-ribo-hexopyranoside and its 3-nitro analog were coupled with glycosyl donors of 3,4-di-O-acetyl-2,6-dideoxy-L-fucopyranose. Successful glycosylations were developed using the fucosyl bromide, activated with silver triflate, and the fucosyl oxysilane, activated with trimethylsilyl triflate. High stereoselectivities for the desired α-1,4 linkage were observed in both cases. The N-trifluoroacetamido disaccharide was deacylated and the amino group oxidized to nitro with dimethyldioxirane. An alternate route based on coupling of the fucosyl bromide with the nitro sugar methyl α-L-decilonitroside also gave the α-linked disaccharide, which is related to oligosaccharides found in the antibiotics cororubicin and arugomycin.

The branched-chain nitro sugar methyl 2,3,6-trideoxy-3-C-methyl-3-nitro-α-D-ribo-hexopyranoside 4 was investigated as a precursor to D-rubranitrose, a nitro sugar found in the antibiotic rubradirin. X-ray cyrstallographic analysis of 4 shows that the pyranose ring adopts the 4 C 1 conformation with the methoxy group at C-1 and the nitro group at C-3 in a 1,3-diaxial relationship. There is an intermolecular hydrogen bond involving a nitro group oxygen of one monosaccharide residue and the C-4 hydroxyl group of the adjacent residue in the crystal lattice. This interaction results in a helical crystal packing. A series of nucleophilic displacement reactions was carried out on the triflate derivative of 4 in an attempt to introduce an axial carbon-oxygen bond at C-4 required for rubranitrose. Displacements with acetate and propionate gave as products the monosaccharide esters with the desired D-xylo configuration.

New procedures are described for the cyclization of allylic 1, 1-dimethylisoureas. Efficient cyclization of the isoureas to give substituted oxazolines occurs with both N-iodosuccinimide and phenylselenenyl triflate. Reductive dehalogenation can be carried out with lithium aluminum hydride.

The addition of phenylselenenyl azide to glycals is carried out under conditions that give 2-deoxy-2-phenylselenoglycosyl azides. This regiochemistry is opposite to that obtained under free-radical conditions, which are known to produce 2-azido-2-deoxyselenoglycosides. The addition reaction is carried out with phenylselenenyl chloride and sodium azide in dimethylformamide, and is stereoselective for trans addition. Tri-O-benzyl-d-glucal and di-O-benzyl-l-rhamnal each gave two addition products, in which the phenylselenyl and azido groups were either trans diaxial or trans diequatorial. Tri-O-benzyl-d-galactal gave only the trans diaxial addition product.

The 77 Se, 13 C and 1 H NMR spectra of the products of phenylselenenyl azide and chloride addition to methylenecyclohexane and cyclohexene are presented. Scalar coupling between 77 Se and 1 H/ 13 C allowed the absolute assignment of the regioisomers in the 1 H and 13 C spectra. Low-temperature 77 Se NMR was used to determine the conformer ratios for 1-azidomethyl- and 1-chloromethyl-1-phenylselenenylcyclohexane anti-Markovnikov addition products

The Diels-Alder reactions of two dienes derived from carbohydrates and their carbocyclic analogs are described. The dienes (2S)-3,4-dihydro-2-methoxy-6-vinyl-2H-pyran (1) and (4R)-3,4-dihydro-4-methoxy-6-vinyl-2H-pyran (2) were synthesied from tri-O-acetyl-D-glucal. Cycloaddition reactions of these dienes, each of which contains a single methoxy group at either the allylic or anomeric position, were carried out with a series of dienophiles including N-phenylmaleimide, dimethyl acetylenedicarboxylate, diethyl azodicarborylate, and N-phenyl-1,2,4-triazoline-3,5-dione. The incorporation of an amine base in the Diels-Alder reactions was found to be essential for the formation of good yields of unrearranged cycloadducts. The diastereofacial selectivities observed for dienes 1 and 2 are compared with those of the analogous carbocyclic dienes methoxy-1-vinylcyclohexene derivatives 3 and 4. Cycloadditions to both the carbohydrate-derived dienes and their carbocyclic analogs were found to aoccur with a preference for addition of the dienophile to the face of the diene opposite the methoxyl group in every case

The addition of phenylselenenyl azide to glycals is carried out under conditions that give 2-deoxy-2-phenylselenoglycosyl azides. This regiochemistry is opposite to that obtained under free-radical conditions, which are known to produce 2-azido-2-deoxyselenoglycosides. The addition reaction is carried out with phenylselenenyl chloride and sodium azide in dimethylformamide, and is stereoselective for trans addition. Tri-O-benzyl-d-glucal and di-O-benzyl-l-rhamnal each gave two addition products, in which the phenylselenyl and azido groups were either trans diaxial or trans diequatorial. Tri-O-benzyl-d-galactal gave only the trans diaxial addition product.

New procedures are described for the cyclization of allylic 1, 1-dimethylisoureas. Efficient cyclization of the isoureas to give substituted oxazolines occurs with both N-iodosuccinimide and phenylselenenyl triflate. Reductive dehalogenation can be carried out with lithium aluminum hydride.

The branched-chain nitro sugar methyl 2,3,6-trideoxy-3-C-methyl-3-nitro-α-D-ribo-hexopyranoside 4 was investigated as a precursor to D-rubranitrose, a nitro sugar found in the antibiotic rubradirin. X-ray cyrstallographic analysis of 4 shows that the pyranose ring adopts the 4 C 1 conformation with the methoxy group at C-1 and the nitro group at C-3 in a 1,3-diaxial relationship. There is an intermolecular hydrogen bond involving a nitro group oxygen of one monosaccharide residue and the C-4 hydroxyl group of the adjacent residue in the crystal lattice. This interaction results in a helical crystal packing. A series of nucleophilic displacement reactions was carried out on the triflate derivative of 4 in an attempt to introduce an axial carbon-oxygen bond at C-4 required for rubranitrose. Displacements with acetate and propionate gave as products the monosaccharide esters with the desired D-xylo configuration.

Derivatives of the branched amino sugar methyl 3-amino-2,3,6-trideoxy-3-C-methyl-α-L-ribo-hexopyranoside and its 3-nitro analog were coupled with glycosyl donors of 3,4-di-O-acetyl-2,6-dideoxy-L-fucopyranose. Successful glycosylations were developed using the fucosyl bromide, activated with silver triflate, and the fucosyl oxysilane, activated with trimethylsilyl triflate. High stereoselectivities for the desired α-1,4 linkage were observed in both cases. The N-trifluoroacetamido disaccharide was deacylated and the amino group oxidized to nitro with dimethyldioxirane. An alternate route based on coupling of the fucosyl bromide with the nitro sugar methyl α-L-decilonitroside also gave the α-linked disaccharide, which is related to oligosaccharides found in the antibiotics cororubicin and arugomycin.

The synthesis of callipeltose, a novel amino sugar with the proposed structure, 4-amino-4,6-dideoxy-2, O -3- C -dimethyl- l -talopyranosyl-3,4-urethane, from l -rhamnose is described. Oxime reduction, carbamate cyclization and selective methylation are key steps. The synthesis supports the assignment of the relative stereochemistry of callipeltose.

The synthesis of methyl α- l -vancosaminide from di- O -acetyl- l -rhamnal is described. The allylic alcohol methyl 2,3,6-trideoxy-3- C -methyl-α- l - threo -hex-2-enopyranoside was prepared from the glycal, 1,5-anhydro-1,2,6-trideoxy-3- C -methyl- l - ribo -hex-1-enitol, and converted to its N , N -dimethylisourea derivative. The cis amino alcohol functionality in vancosamine was introduced by the electrophilic cyclization of the isourea, followed by hydrolysis of the resulting oxazoline.

The addition of benzenesulfinic acid to glycals was investigated under various conditions, and optimized yields of the glycosyl phenylsulfone products were obtained in the presence of tin tetrachloride as a catalyst. Double bond shift (Ferrier rearrangement) occurred in all cases except amicetal, which lacks a substituent at the allylic carbon. Glycosylation of benzenesulfinic acid with 1,2-dibromides was carried out using silver triflate as the promoter, and gave sulfinate esters as products by reaction at oxygen rather than at sulfur. The sulfinate esters were obtained as mixtures of stereoisomers at the stereogenic sulfur atom. Trapping of the sulfinates with carboxylate nucleophiles was observed during attempted oxidation with MCPBA.

A series of substituted 2-allyl-1,1-dimethylisoureas (allyl N,N-dimethylcarbamimidates) was prepared by the reaction of the corresponding allylic alcohols with dimethylcyanamide in the presence of sodium hydride. Treatment of the isoureas with mercuric acetate in acetonitrile, followed by reduction with sodium borohydride, afforded substituted 4,5-dihydrooxazoles. Thermal rearrangement of the 1,1-dimethylisoureas occurred in refluxing xylene to give trisubstituted ureas

A series of carbohydrate-derived dienes with different patterns of substitution on the pyranose ring were synthesized and their Diels-Alder reactions investigated. The diene moiety was incorporated into the pyranose ring by oxidation of 4-O-methanesulfonate esters of sugar derivatives to enals, followed by Witting alkenation. This new class of dienes underwent cycloaddition with maleimide or its N-phenyl derivative to give annulated pyranosides. The Diels-Alder reactions were highly stereoselective, giving single products in some cases. Structural analysis of the reaction products was carried out by NMR spectroscopy and X-ray crystallography. The results indicated a strong preference for the formation of the products resulting from addition of the dienophile to the face of the diene opposite the anomeric center. In cases where the anomeric and allylic substituents on the diene occupied opposite faces, addition of the dienophile occurred predominantly from the face opposite the more remote anomeric center

Reaction of alkenes and alkenols with N-iodosuccinimide (NIS) and benzenesulfinic acid in dichloromethane at room temperature affords vic-iodophenylsulfonyl adducts in good to high yields. Treatment of the iodosulfones with neutral alumina in dichloromethane at room temperature results in dehydroiodination to give the corresponding vinyl sulfones in high yield and purity by this convenient two-step procedure. Application of the iodosulfonation–dehydroiodination sequence to allylic alcohols and silyl ethers gave γ-oxygenated, α,β-unsaturated phenylsulfones, while the attempted iodosulfonation of glycals, as intermediates to vinyl sulfones, resulted in addition of benzenesulfinic acid with double bond shift (Ferrier rearrangement). Key words: iodosulfonation, vinyl sulfones, benzenesulfinic acid, N-iodosuccinimide, dehydroiodination.