Search

Disaccharide corresponding to the disaccharide unit of apoptolidin A is synthesized. The regio- and stereoselective TBS-OTf-promoted [beta]-glycosidation reaction of 2,6-dideoxy-2-iodo-[beta]-glucopyranosyl acetate and p-methoxybenzyl 2,6-dideoxy-2-iodo-3-C-methyl-[alpha]-mannopyranoside are used for this synthesis.

An efficient indium-mediated one-pot synthesis of cis-2,6-disubstituted tetrahydropyrans from substituted allyl iodides is reported. The environmentally beningn protocol takes place in aqueous media under conditions that tolerate acid-sensitive alcohol protecting groups.

Trifluoroethanol was elaborated via a telescoped sequence involving a metalated difluoroenol, a difluoroallylic alcohol, [2,3]-Witting rearrangement requiring minimal intermediate purification to a number of cyclooctenone intermediates. The epoxidation of these intermediates followed by transannular ring opening or dihydroxylation and then transannular hemiacetalization have delivered novel bicyclic analogues of pentopyranoses.

The access to piperidine homoazasugars (dideoxyiminoheptitols) from pyranoses through formal one-carbon chain elongation and exchange of the ring oxygen with the NH group is described. Cleavage of the thiazole residue attached to C2 of the piperidine ring reveals the formyl group, which is reduced to hydroxymethyl to give the target homoazasugar.

A computational study of the conformational space of methyl 2,4-diacetyl-[beta]-D-xylopyranoside is presented. The [.sup.1][C.sub.4] and [.sup.2][S.sub.o] forms are stabilized by hydrogen bonding and anomeric effects and the [.sup.4][C.sub.1] chair has the smallest steric repulsion whereas the skew-boats have the largest.

A systematic study of C-glycosylations of acetals related to mannose and other pyranoses was conducted. Studies of pentopyranoses bearing alkoxy groups at C-2, C-3, and C-4 showed that alkoxy groups exerted powerful influences on selectivity.

A newly developed strategy which pivots on a new electrophilic pyrone derivative which could be readily prepared on a multigram scale is used to synthesize 3-substituted-2-pyrones. The electrophilic pyrone derivative is observed to perform very competently in metal-catalyzed cross-coupling reactions with a variety of nucleophiles.

Car-Parrinello metadynamics simulations are used for obtaining the conformational free-energy surface (FES) of a [beta]-D-mannopyranose molecule associated with the ideal Stoddart conformational diagram. The analysis of the computed FES has supported the proposed [super 1][S.sub.5] -> [B.sub.2,5] -> [super 0][S.sub.2] catalytic itinerary, which has shown that the degree of preactivation of the substrate in glycoside hydrolases (GHs) is related to the properties of an isolated sugar ring.

A newly developed strategy toward ketopyranosides based on a carbene-mediated activation of the anomeric C-H bond of carbohydrates is described. The formation of a new carbon-carbon bond after a glycosylation step in the method is observed to facilitate the preparation of both [alpha]- and [beta]-ketopyranosides from advanced precursors.

A highly regioselective one-pot transformation of 2-azido-2-deoxy-1,3,4,6-tetra-O-trimethylsilyl-D-glucopyranose by sequential additions of various reagents is analyzed, which has produced the fully protected derivatives and the 1-, 3-, 4-, as well as 6-alcohols.

Cyclic voltammetry is used for the electrochemical characterization of 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-2-(pyrro-1-yl)-[beta]-D-glucopyranose (Py-GSATA). Molecular modeling is used for analyzing the stability and feasibility of the electrogenerated species in order to explain the dimer cation stability in the solution.

Two methods to efficiently synthesize kaempferol 3-O-(3'',6''-di-O-E-p-coumaroyl)-[beta]-D-glucopyranoside (1), an optimal metabolite of Scots pine seedlings for protection of deep-lying tissue against damaging UV-B which represents a typical acylated flavonol 3-O-glycoside are presented. A variety of the glycosyl o-hexanylbenzoates equipped with the 2-O-benzoyl group are found to be highly efficient donors for construction of the flavonol 3-O-glycosidic linkages.

A novel route is developed for 2' ,3' -dideoxy-[beta]-L-erythro-hexopyranosyl nucleosides equipped with a 1' -([N.sup.6]-benzolyadenin-9-yl) or a 1' -(thymin-1-yl) moiety. The synthesis of the enantiopure sugar moiety is performed by a de novo approach based on a domino reaction as the main step and N-glycosylation is analyzed by either nucleobase-transfer mechanism or in situ anomerization.

The free energy landscape of pyranose ring of L-iduronic acid (IdoA), a major constituent of the anticoagulant heparin and two related monosaccharides from extensive microsecond simulations are calculated to understand the equilibrium of multiple ring puckets. The results from the free-energy calculations could be used to enhance the computational methods and provide a novel route to carbohydrate mimetic biomaterials and pharmaceuticals.

The Free Energies from Adaptive Reaction Coordinate Forces (FEARCF) in SCC-DFTB QM/MM non-Boltzmann simulations is applied to the six-membered glucopyranose ring located in an eight-membered [beta] 1-4 linked octaose oligosaccharide (cellooctaose). The calculated free energy for the ring puckering of the glucopyranose ring at the - 1 position in vacuum, in water, and bound to the protein revealed that the protein induces [super 4]E and [super 4][H.sub.3] conformations that are much more stable than the usually preferred [super 4][C.sub.1] conformer.

The examination of the pH-dependent mutarotation of 1-thioaldopyranoses in aqueous media is presented. 1-Thio-D-mannopyranose and 1-thio-D-altropyranose has displayed very strong pH dependence where the anomeric equilibrium ratios have changed from a preference for the [beta]-anomer at lower pH to the [alpha]-anomer at higher pH.

Mangiferin, isomangiferin and homomangiferin, the xanthone C-glycosides with a wide spectrum of pharmacological effects, are prepared, featuring a C-glycosylation of a xanthene derivative with perbenzylglucopyranosyl N-phenyltrifluoroacetimidate.

An enantioselective synthesis of the antifungal natural product (+)-ambruticin S is achieved starting with the me thyl [alpha]-D-glucopyranoside, (R)-Roche ester, and (S)-glycidol as chirons, which has encompassed seven of the 10 stereogenic centers of the target molecule. The strategy for the construction of the dihydropyran subunit has involved a highly syn-selective Lewis acid catalyzed 6-endo-trig cyclization and other key steps in the synthesis has featured an epoxide opening with a dithiane anion, two efficient phosphonamide-anion based olefinations, and a late-stage C-glycosylation.

Density functional theory is used for calculating [super 1]H-[super 1]H, [super 13]C-[super 1]H and [super 13]C-[super 13]C NMR spin-coupling constants in four model compounds that mimic [alpha]-gluco, [beta]-gluco, [alpha]-allo and [beta]-allo 2-acetamido-2-deoxy-D-aldohexopyranosyl ring configurations in order to analyze the effects of C1 and C3 configuration adjacent to the N-acetyl group on coupling behavior. The application is shown in the analysis of J-couplings measured within the N-acetyl side-chain of a [super 13]C-labeled methyl N-acetyl-[alpha]-D-glucosaminide.

N-heterocyclic carbene catalyzed variant of the Claisen rearrangement was utilized to perform a highly enantioselective annulation reaction between enols and ynals in presence of a chiral azolium salt to obtain enantiomerically enriched dihydropyranones. The catalytic system which requires no added base to generate the putative NHC-catalyst could be applied to the synthesis of enantioenriched kojic acid derivatives.

A full series of 1,6-anhydro-2,3,4-trideoxy-4-fluoro-2,3-epimino-[beta]-D-hexopyranoses is prepared, where the key step is the reaction of azido sulfonates possessing a free C-4 hydroxyl with DAST and subsequent LiAl[H.sub.4] reduction. Nucleophilic displacement of the hydroxyl activated by DAST has proceeded without rearrangement and the synthesis of D-mannoepimine from 3-benzylamino derivative is developed.

The transient kinetics and primary and solvent kinetic isotope effects of the mutant in which His167 is replaced with Ala (H167A) are examined to demonstrate the functional role of the 8a-N3-histidyl flavin adenine dinucleotide (FAD) linkage and to gain insights into the reaction mechanism of pyranose 2-oxidase (P2O) from Trametes multicolor. The results provide insight into significance of the covalent linkage for a reductive half-reaction in which the FAD cofactor is reduced by D-glucose and unimportant role for an oxidative half-reaction in which oxygen reacts with the reduced FAD to generate [H.sub.2][O.sub.2].

The oxidative cleavage of 4,6-O-benzylidene acetals of glycopyranosides using dimethyldioxirane (DMDO) has led to the corresponding hydroxy-benzoates. The oxidative fragmentation has provided the 6- or 4-hydroxyl derivatives in a highly regioselective manner by choosing proper neighboring protecting groups.

The reeling of an axis molecule into a macrocyclic host molecule located at the end of the axis is studied to control the shuttling of a macrocycle. The tumbling of the altro-[alpha]-cyclodextrin ([alpha]-CD) stopper containing one altropyranose unit and five glucopyranose units played a critical role to control the shuttling of a rotor by reeling the axis molecule into a host molecule at the end of an axis.

The development of a versatile synthetic route toward peptide mimetics build on 2-amino pyranose scaffolds is described. The methods have given access to molecules that position the selected binding elements in various 3D orientations on a pyranose scaffold and are applied for producing a diverse library of monosaccharide-based mimetics.

The interaction energy between benzene and the different carbohydrates is determined by using Calvet microcalorimetry, as the enthalpy of solvation. The elevated stabilization energy of 1,2,3,4,6-penta-O-acetyl-[beta]-D-galactopyranose ([beta]-[Ac.sub.5]Gal) is because of the interaction between benzene and the methyl groups of the acetyls and hence methoxy and acetyl substituents have different effects on the protons of the pyranose ring.

The various [beta]- and [alpha]-directing effects of the different groups of donors and acceptors present in mannipyranosylations are discussed. The strongly electron-withdrawing sulfonyl groups are shown to lead to higher stability of the triflates, as compared to the weak sulfonyl groups.

The flavoenzyme uridine 5'-diphosphate galactopyranose mutase (UGM of Glf) has catalyzed the interconversion of UDP-galactopyranose and UDP-galactofuranose and the mechanistic studies of UGM have shown a novel role for the flavin. The X-ray crystal structures of the substrate-bound enzyme are described in oxidized and reduced forms, respectively.

A stopped-flow technique was used to study the reduction kinetics of pyranose 2-oxidase (P2O) from Trametes multicolor by D-glucose and 2-d-D-glucose at pH 7.0. The movement of the active site loop when oxygen is present is proposed to facilitate the release of the sugar product in P2O and the overall turnover of the reaction is limited by the steps of flavin reduction and decay of C4a-hydroperoxy-flavin adenine dinucleotide (FAD).

The mononuclear copper enzyme, galactose oxidase, is examined under steady-state conditions via [O.sub.2]-consumption assays by using 1-O-methyl-[alpha]-D-galactopyranoside as the sugar substrate to produce an aldehyde at the C-6 position. The results have shown fundamental differences in the hydrogen transfer step from the carbon of substrate vs the oxygen of reduced cofactor during the reductive and oxidative half-reactions of galactose oxidase.

A convergent strategy is used for achieving an effective, asymmetric total synthesis of the antitumor antibiotic (-)-okilactomycin, as well as assignment of the absolute configuration. The studies have included a diastereoselective oxy-Cope rearrangement/oxidation sequence to install the C(1) and C(13) stereogenic centers, a Petasis-Ferrier union/rearrangement to construct the tetrahydropyranone inscribed within the 13-membered macrocycle ring and a ring-closing metathesis reaction to generate the macrocyclic ring.

D-mannose and L-arabinose derivatives for the D- and L-series are used as starting materials for the synthesis of both enantiomers of a 4-O-6-S-[alpha]-cyanobenzylidene-protected 6-thiorhamnopyranosyl thioglycoside. The obtained 6-thio-[beta]-mannosides are converted to the [beta]-rhamnopyranosides via desulfurization and concomitant debenzylation with Raney nickel.

A ring-expansion methodology for the generation of aryl septanosides, arabinofuranosyl and glucopyranosyl, septanoside disaccharides, and azido septanosides is reported. The results consolidated the generality of the oxyglycal ring-expansion approach to prepare septanosides that have different substituents at their reducing ends.

A facile and efficient two-step synthesis of 2-acetamido-2-deoxy-[beta]-D-glucopyranosides from commercial D-Glc-NAc via the 5,6-O-isopropylidene furanose acetonide derivative for preparing the aminosugars is reported. The method could be applied to muramic acid chemistry to generate carbohydrate targets related to bacterial cell wall research.

The synthesis and structural study of cyclohexyl 4'-O-cyclohexyl-[beta]-D-glucopyranosyl-1(1->4)-[beta]-D-glucopyranoside or, alternatively, 1,4'-dicyclohexyl cellobioside is presented. The studies have shown that the hydrogen bonds between parallel molecules are unique.

Spiropyran derivatives having good photophysical characteristics are described as the excellent photoswitchable fluorophores. This fluorophore is used for achieving photoactuated unimolecular logical switching attained reconstruction (PULSAR) microscopy.

The stereoselective formation of the [alpha]-GaINAc-Ser, [beta]-GlcNAc-Ser, and [alpha]-Man-Ser linkages is described using the ring opening of aziridine-2-carboxamide with pyranose C1-O-nculeophiles. The studies have shown that this process has provided good levels of anomeric selectivity and is tolerant to the native C2-NHA group.

The stereoselective reduction of hexopyranos-5'-yl radicals in [alpha]-D-Hexp-(1->4)-D-Hexp into [beta]-L-Hexp-(1->4)-D-Hexp disaccharides in a single step with high diastereoselectivity is described. The radicals are generated from a 6-O-yl radical located in the other monosaccharic unit through a 1,8-hydrogen atom transfer.

A highly stereoselective first total synthesis of (+)-varitriol, an antitumor natural product is reported. The carbohydrate subunit was generated from commercially available methyl [alpha],D-mannopyranoside and 2,6-dihydroxybenzoic acid.

The intrinsic conformational preferences and structures of the branched trimannoside, [alpha]-phenyl 3,6-di-O-([alpha]-D-mannopyranosyl)-[alpha]-D-mannopyranoside and its singly hydrated complex, are examined in the gas phase isolated at low temperature in a molecular beam expansion. The creation of a water pocket motif localized at the bisecting axis of the trimannoside is similar to the structure of more complex N-glycans in water, indicating a general role for the bisecting OH4 group in the central mannose unit.

An efficient method is described for the synthesis of pyranose-, nucleoside-, amino acid- and polyhydric-based seleninates and selenonates, as well as some unusual coupling reactions with nucleophilic functionality found in proteins and enzyme active sites. The stability of many of the new seleninates is attributed to the slow rate of selenoxy retro-ene elimination expected for systems width a [beta]-oxygen substituent.

The synthesis of 1,6-anhydro-[beta]-L-hexopyranosyl derivatives are described for the preparation of L-sugars. The studies have shown that as 1,6-anhydro derivatives are obtained, dithioethylene bridge removal and double-bond dihydroxylation has given access to protected L-allose and L-glucose in stereoselective fashion and high yields.

NMR spectroscopy is used for studying the migration of acetyl, pivaloyl, and benzoyl protective groups and their relative stabilities at variable pH for a series of [beta]-D-galactopyranoses. The results have provided new insights into the acid and base stabilities of commonly used ester protecting groups and the phenomenon of acyl group migration and have proved useful in the planning of synthesis strategies.

Several ab initio quantum chemical calculations are conducted to explain the synthesis, as well as the crystal structures of N-([beta]-D-glycopyranosyl)haloacetamides. The various conformational preferences of the aglycon moiety in models and analogs of GlcNAc-Asn linkage are also discussed.

A photochemical method for introducing a tetrahydropyran (THP) group to a hydroxyl group is developed. The reaction could be conducted by using photochemical reactors such as anthraquinone intermediate, ambient fluorescent lighting, or sunlight and is only slightly sensitive to the presence of oxygen.