α-D-Glycosyl-Substituted α,α-D-Trehaloses with (1 → 4)-Linkage: Syntheses and NMR Investigations

Two symmetrical trehalose glycosyl ‘acceptors’ 4 and 6 were prepared and three of the unsymmetrical type, 8 , 10 , and 11 . Glucosylation of symmetrical ‘acceptor’ 4 gave a higher yield of trisaccharide (44%) than protect ve-group manipulation, namely via selective debenzylidenation 2 → 9 or monoacetylation 2 → 5 which proceeded in moderate yields (33–34%). A comparison of catalysts in the cis-glucosylation of trehalose ‘acceptor’ 10 with tetra-O-benzyl-β-D -glucopyranosyl fluoride 13 profiled triflic anhydride ((Tf)₂O) as a new reactive promoter yielding 92% of trisaccharide 14 , deblocking gave the target saccharide α-D -glucopyranosyI-( 1 → 4 )-α,α-D -trehalose. ¹H-NMR spectra of most compounds were analyzed extensively. The use of the ID TOCSY technique is advocated for its time efficiency, if needed supplemented by ROESY experiments.     

Synthesis and properties of stereoregular 2,3,4-tri-o-acetyl-[1 → 6]-α-D-gluco-, -manno-, and -galactopyranans

Polymerization 1,6-anhydro-2,3,4-tri-O-benzyl-β-D -mannopyranose at ?60°C with phosphorus pentafluoride (0.9 mole-%) gives stereoregular 2,3,4-tri-O-benzyl-[1 → 6]-α-D -mannopyranan with substantially higher viscosity ([η] = 2.8 dl/g) than the corresponding gluco- and glactopyranan derivatives prepared similarly. Debenzylation with sodium in liquid ammonia produces stereoregular [1 → 6]-α-D -mannopyranan of viscosity up to [η] = 0.54 dl/g. Stereoregular 2,3,4-tri-O-acetyl-[1 → 6]-α-D -glycopyranans are most simply prepared by acetylation of the corresponding crude [1 → 6]-α-D -glycopyranans obtained directly from the debenzylation reaction. The galactan is extremely difficult to acetylate by conventional methods if isolated in a pure form. Physical and spectral properties of these highly stereoregular synthetic 2,3,4-tri-O-acetyl-[1 → 6]-α-D -glycopyranans are presented. Optical rotary dispersion curves of 2,3,4, tri-O-acetyl-[1 → 6]-α-D -glycopyranans show small Cotton effects in the 200–230 nm region, superimposed on strong background rotation. Circular dichroism spectra show a single n →^* acetate absorption band for each polymer. The sign of the band appears to be determined largely by the C-2 configuration. Stereoregular 2,3,4-tri-O-acetyl-[1 → 6]-α-D -glycopyranans in 2,2,2-trifluoroethanol solution are likely to possess a random rather than helical conformation.     

Oligosaccharides Related to Tumor-Associate Antigens. Part 2. Conformational analysis of the trisaccharide α-L-Fucp-(1→2)-β-D-Galp-(1→3)-β-D-GalpNAc,epitope structure recognized by the MBr1 antibody

The conformational space of the trisaccharide α-L -Fuc-(1→2)-β- D -Gal-(1→3)-β -D -GalNAc-1-OPr ( 2 ) and of its component disaccharide moieties α -L -Fuc-(1→2)-β -D -Gal-1-OMe ( 3 ) and β -D -Gal-(1→3)-β- D -GalNAc-1-OPr ( 4 ) was investigated with the aid of molecular-mechanics energy minimizations and molecular-dynamics simulations. These calculations suggested the occurrence of two conformations for each compound characterized by different ? and Ψ glycosidic angles. However, ¹H-NMR investigation of D₂O solutions of 2–4 indicated a sure preference for one of the two conformers with a contribution of the other one ranging from negligible to low.     

Synthesis of propyl O-(α-L-rhamnopyranosyl)-(1→3)-[2,4-di-O-(2s-methylbutyryl)-α-L-rhamnopyranosyl]-(1→2)=(3-O-acetyl-β-D-glucopyranosyl)-(1→2)-βp-D-fucopyranoside,the tetrasaccharide moiety of Tricolorin A

Propyl O-(α-L-rhamnopyranosyl)-(1→3)-[2,4di-O-(2s-methylbutyryl)-α-L-rhamnopyranosyl]-(1→2)-(3-O-acetyl-β-glucopyranosyl)-(1→2)-β-D-fucopyranoside (1), the tetrasaccharide moiety of Ricolorin A, was synthesized in total 23 steps with a longest linear sequence of 10 steps, and overall yield of 3.7% from D-Glucose. The isomerization of the dioxolane-type benzylidene in the prance of NIS/AgOTf was observed. Tetrasaccharide 1 exhibited no activity against the cultured P388 cell as Tricolorin A did.     

Oligosaccharides Related to Tumor-Associated Antigens. Part I. Synthesis of the propyl glycoside of the trisaccharide α-L-Fucp-(1 → 2)-β-D-Galp-(1 → 3)-β-D-GalpNAc,component of a tumor antigen recognized by the antibody MBr1

The synthesis of the trisaccharide α-L -Fucp-(1 → 2)-β-D -Galp-(1 → 3)-β-D -GalpNAc-1-OPr ( 2 ) is described. The N-acetylgalactosamine 6 was obtained from 4 by an intramolecular displacement of a (trifluoromethyl)sulfonyloxy by a pivaloyloxy group with its concomitant migration from position 3 to position 4 (Scheme 1). The galactosyl donor 9 was obtained from 7 via 8 by regioselective opening of the orthoester function with AcOH/pyridine followed by treatment with CCl₃CN and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (Scheme 2). Glycosylation of 6 with 9 in the presence of BF₃ · OEt₂ gave the disaccharide 10 . Selective deprotection of 10 at O? C(2′) followed by glycosylation with 12 and by standard deprotection afforded the title trisaccharide 2 (Scheme 3). Preliminary biological testing showed that 2 is able to inhibit the binding of the monoclonal antibody MBrl to the target tumor cells MCF7 in a dose-dependent manner.     

Isolierung und Strukturaufklärung von Neapolitanose (O-β-D-Glucopyranosyl-(1→2)-O-[β-D-glucopyranosyl-(1→6)]-(D-glucose), einem neuen Trisaccharid aus den Stempeln von Gartenkrokussen (Crocus neapolitanus var.)

Isolation and Structure Elucidation of Neapolitanose (O-β-D -Glucopyranosyl-(1→2)-O-[β-D -glucopyranosyl-(1→6)]-D -glucose), New Trisaccharide from the Stigmas of Garden Crocusses (Crocus neapolitanus var.) From the stigmas of Crocus neapolitanus var. ‘Blue Bird’ two new crocetin glycosyl esters were isolated. They contained a hitherto unknown trisaccharide. For the structure elucidation a homonuclear 2D-¹H-NMR-shift-correlation experiment was carried out with the peracetate of the isolated trisaccharide. This experiment revealed that the carbohydrate is O-β-D -glucopyranosyl-(1→2)-O-[β-D -glucopyranosyl-(1→6))]-D -glucose, for which we suggest the name ‘neapolitanose’. The two new C₂₀-carotenoids from Crocus neapolitanus are crocetin (β-gentiobiosyl) (β-neapolitanosyl) ester ( 4 ) and crocetin di(β-neapolitanosyl) ester ( 5 ).     

Synthesis of 15-hydroxy-15(14→8)abeo-5α,(8S)-cholestane-3,14-dione

The synthesis of 15α-hydroxy-15(14→8)abeo-5α,(8S)-cholestane-3,14-dione (1) fromcholesterol in ten steps was described.The key step is the intramolecular aldol condensationof 3,14-dioxo-14,15-seco-5α-cholestan-15-al (3).     

Multichain copoly(α-amino acid). II. Preparation and properties of multi-Nϵ-poly(γ-benzyl-L-glutamyl)copoly(L-lysine γ-methyl-L-glutamate)

A number of multi-N^?-poly(γ-benzyl-L -glutamyl)copoly(L -lysine γ-methyl-L -glutamate)s with branches having various degrees of polymerization and with various intervals of the grafting sites in the core molecule were prepared in N,N-dimethylformamide containing dimethyl sulfoxide by the reaction of N-carboxy anhydride of γ-benzyl L -glutamate with random copoly(L -lysine γ-methyl-L -glutamate)s of different composition with various anhydride-initiator ratios. The relationship between the intrinsic viscosity measured in a coil solvent, dichloroacetic acid (DCA), and the number-average molecular weight determined by osmometry was found to be expressed by the Mark–Houwink–Sakurada equation for the multichain copoly(α-amino acid)s which were made from the same polymeric initiator. The observed α values of the multichain copoly(α-amino acid)s in the equation were lower than that of linear poly(γ-benzyl-L -glutamate). The solvent induced helix–coil transition of the multichain copolymer was investigated in the chloroform?DCA system by the ORD technique. Two kinds of transition regions were clearly distinguished: The α-helices of the core molecules underwent the transition at lower DCA concentration and those of the branch chains at higher DCA concentration. The reduced viscosity of the multichain copoly-(α-amino acid) increased slightly between the two transition regions, in contrast to the large decrease in the reduced viscosity of linear poly(γ-benzyl-L -glutamate) during the helix–coil transition.     

Synthese und Eigenschaften von 2-(α-Hydroxyalkyl)-und 2-(α-alkoxycarbonyl)-substituierten 4-Methyl-5-(β-hydroxyäthyl)-thiazolen und -thiazoliumsalzen

Condensation of the tetrahydropyranyl ether of the α-hydroxyalkyl-thioamides with 3-bromo-4-hydroxy-2-pentanones yields DL -2-(α-hydroxyalkyl)-4-methyl-5-(β-hydroxyethyl)-thiazoles. By oxidation with chromic anhydride 2-hydroxymethyl-4-methyl-5-(β-acetoxyethyl)-thiazole yields the corresponding 2-formyl derivative. The latter compound reacted with GRIGNARD complexes gives the homologous DL -2-(α-hydroxyalkyl)-4-methyl-5-(β-hydroxyethyl)-thiazoles. This is a general method for the synthesis of the thiazole part of the «active aldehydes». 2-Acetyl-4-methyl-5-(β-hydroxyethyl)-thiazole is also obtained by chromic oxidation of the suitable methylthiazol-2-yl-carbinol. The condensation of the thioamides obtained from the α-ethoxycarbonyl-nitriles with 3-bromo-5-acetoxy-2-pentanone results in the DL -2-(α-ethoxycarbonyl-alkyl)-4-methyl-5-(β-acetoxyethyl)-thiazoles. The α-hydroxyl function is introduced into the 2-(α-ethoxycarbonyl-alkyl) group by chlorination with sulfuryl chloride and replacement of the introduced chlorine by acetate. The latter compounds are the esters of the thiazole part of the «active α-oxo-carboxylic acids» (e.g. active pyruvate, etc.). The reaction of 2-(α-hydroxyalkyl)-4-methyl-5-(β-hydroxyethyl)-thiazoles and 2-(α-ethoxycarbonyl-α-acetoxy-alkyl)-4-methyl-5-(β-acetoxyethyl)-thiazoles, respectively, with alkyl, alkenyl and aralkyl haloids, or with 2-methyl-4-amino-5-bromomethyl-pyrimidine hydrobromide results in the quaternary thiazolium compounds belonging to the group of the active aldehydes, active α-oxo-carboxylic acids, etc. According to this method 2-hydroxymethyl-thiamine bromide hydro-bromide has been synthesized, which can be considered as the pyrophosphate-free «active formal-dehyde». The 2-α-hydrogen atom in 2-(α-hydroxyalkyl)-thiazolium compounds cannot be replaced by deuterium under conditions similar to those used for the H → D exchange in thiamine. The main peaks in the mass spectra of 2-(α-hydroxyalkyl) substituted thiazoles and thiazolium quaternary salts are listed.     

3-Azawurtzitan und 3(4 → 5)abeo-3-Azawurtzitan

3-Azawurtzitane and 3(4 → 5)abeo-3-Azawurtzitane 3-Azawurtzitane (14) and 3(4 → 5)abeo-3-azawurtzitane (15) as well as derivatives thereof are described. The known tricyclic unsaturated ketone 1 was transformed to the properly functionalized endo-amines 3, 5 and 12. Entry to the azawurtzitane system and its corresponding abeo-compounds was achieved by three different cyclization procedures: aminomercuration with mercuric acetate in water (3 → 14, 5 → 16) , olefin amination with mercuric acetate in dimethyl sulfoxide (3 → 18, 5 → 20 + 21) and intramolecular attack at an epoxide (12 → 24 + 25). Molecular rearrangements of 3-azawurtzitanes to 3(4 → 5)abeo-3-azawurtzitanes and vice versa are described involving neighbouring group participation of the N (3) atom.     

Cationic polymerization of α-methylstyrene from polydienes. I. Synthesis and characterization of poly(butadiene-g-α-methylstyrene) copolymers

The preparation of poly(butadiene-g-α-methylstyrene) copolymers was investigated with three different alkylaluminum coinitiators. The alkylaluminum compounds in conjunction with polybutadiene which contained a low concentration of labile chlorine atoms initiated the polymerization of α-methylstyrene to produce graft copolymers. Trimethylaluminum gave higher grafting efficiencies than diethylaluminum chloride at comparable monomer conversions. Triethylaluminum produced only very low monomer conversions (<5%), even at long reaction times, and for this reason was not studied extensively. The number of grafts per polybutadiene backbone was determined for a number of copolymers and found to increase slightly as the allylic chlorine concentration in the polybutadiene backbone was increased. In all cases, however, only a low percentage of the available labile chlorine sites along the polybutadiene backbone resulted in grafted α-methylstyrene side chains. The addition of small quantities of water to the polymerization solvent greatly enhanced the grafting rate and ultimate monomer conversion during the synthesis of these poly(butadiene-g-α-methylstyrene) copolymers. The mechanistic role of water during these grafting reactions is unknown at the present time.     

Ring-opening metathesis polymerization of new α-norbornenyl poly(ε-caprolactone) macromonomers

Poly(ε-caprolactone) (PCL) macromonomers capped by a polymerizable norbornene end-group have been synthesized and (co)polymerized by ring-opening metathesis with formation of graft copolymers and polymacromonomers. α-Norbornenyl PCL macromonomers have been synthesized by ring opening polymerization (ROP) of ε-caprolactone (εCL) initiated by 2-diethylaluminoxymethyl-5-norbornene. Copolymerization of these PCL macromonomers with norbornene and polymerizable derivatives has been catalyzed by the [RuCl₂(p-cymene)]₂ PCy₃/(trimethylsilyl)diazomethane complex yielding a series of poly(norbornene)-graft-poly(ε-caprolactone) copolymers. These new graft copolymers have been characterized by a set of analytical methods, i.e., SEC, ¹H-NMR, FTIR, DSC, and TGA. Furthermore, PCL macromonomers have been polymerized into high molecular weight comb chains of narrow molecular weight distribution (M_w/M_n = 1.10) within high yields (90%). © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 2447–2455, 1999     

Highly Efficient Regio- and Stereoselective Synthesis of β-（1 →6）-Branched β-（1 →3）-Linked Glucohexaose and Its Analogue

A β-（1→）6）-branched β-（1→）3）-linked glucohexaose （1） and its lauryl glycoside （2）, present in many biologically active polysaccharides from traditional herbal medicines such as Ganoderma lucidum, Schizophyllum commune and Lentinus edodes, were highly efficiently synthesized. Coupling of 2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl- （1--）3）-2-O-benzoyl-4,6-O-benzylidene-a-D-glucopyranosyl trichloroacetimidate （7） with 3,6-branched acceptors 8 and 12 gave β-（1→）3）-linked pentasaccharides （9） and （13）, then via simple chemical transformation 4＇,6＇-OH pentasaccharide acceptors 10 and 14 were obtained. Regio- and stereoselective coupling of 3 with 10 and 14 gave β-（1→）3）-linked hexasaccharides （11） and （15） as the major products. Deprotection of 11 and 15 provided the target sugar 1 and 2. Thus, a new method for the preparation of this kind of compounds was developed.     

Grafting to Vinylpyrrolidone Polymers and Copolymers by the Ceric lon Method

Polymers and copolymers of vinylpyrrolidone were investigated as grafting substrates for methyl methacrylate using the ceric ion method. Ceric ion readily initiates methyl methacrylate grafting to commercial poly (vinylpyrrolidone) (PVP) of 360,000 nominal molecular weight. The resulting graft copolymer was surprisingly found to be an ABA triblock system with PVP in the center block. This conclusion is supported by three key pieces of evidence: first, selective degradation of the PVP/MMA graft copolymer showed two PMMA grafts per PVP chain: second, blocking of what are apparently hydroxylic or glycolic PVP end groups by reaction with phenyl isocyanate rendered the PVP unreactive to ceric ion grafting; third, if the PVP is prepared by methods which preclude formation of hydroxylic end groups, the PVP is unreactive to ceric ion grafting.

Vinylpyrrolidone polymers can be made graftable via ceric ion if N-methacryloyl-D-glucosamine (NMAG) is incorporated as a comonomer in the PVP backbone. Regardless of the method of preparation, incorporation of NMAG provides grafting sites which are highly reactive to ceric ion. At copolymer compositions up to 10 mole % NMAG, the methyl methacrylate graft copolymers are soluble in organic solvents. Above 10 mole % NMAG, the grafting reaction leads to cross-linking and formation of intractable gels.     

5-(α-Fluorovinyl)tryptamines and 5-(α-Fluorovinyl)-3-(N-methyl-1′,2′,5′,6′,-tetrahydropyridin-3′- and -4′-yl)indoles—5-(α-Fluorovinyl)tryptamines

5-(α-Fluorovinyl)tryptamines 4a, 4b and 5-(α-fluorovinyl)-3-(N-methyl-1′,2′,5′,6′-tetrahydropyridin-3′- and -4′-yl) indoles 5a, 5b were synthesized using 5-(α-fluorovinyl)indole ( 7 ). The target compounds are bioisosteres of 5-carboxyamido substituted tryptamines and their tetrahydropyridyl analogs.     

Synthesis of ion-exchange membranes by radiation-induced multiple grafting of methyl α,β,β-trifluoroacrylate

Methyl α,β,β-trifluoroacrylate (MTFA) was grafted onto polymer films with the multiple grafting technique initiated by α-rays: the yields were similar to those of the single-step grafting procedure with any irradiation dose. Grafted polymer obtained in the single-step experiments were distributed mainly near the film surface, whereas graft polymer from the multiple grafting experiments were distributed uniformly in the film at graft yields greater than 20%. The electric resistance of the hydrolyzed multiple graft polymer film in a 2N NaOH solution was much lower than that of one-step graft film at the same graft yield.     

Synthesis of poly-α,α-diphenylglycine. II. Cationic polymerization of 4,4-diphenyl-Δ2-1,2,3-triazolin-5-one

4,4-Diphenyl-Δ²-1,2,3-triazolin-5-one (I) was found to undergo a cationic polymerization under the influence of boron trifluoride etherate in an anhydrous solvent. The poly-α,α-diphenylglycine (III) thus formed contained a larger amount of oligomers than the polymer obtained by thermal decomposition as described in the preceding paper. The molecular weight distribution was further shown to depend on the monomer and catalyst concentration and on the nature of the solvent. A mechanistic rationalization is proposed, involving propagating triazolinium ion pairs (VII) which are not interrupted by chain transfer or termination in the absence of water or alcohol. In the presence of water or alcohol, no polymerization occurred, but the normal acid-catalyzed decomposition products (IV and V) were then obtained. 1-Methyl-4,4-diphenyl-Δ²-1,2,3-triazolin-5-one (VIII) was also treated with BF₃ · OEt₂ in a dry solvent at room temperature and furnished 1-methyl-3-phenyl-indolin-2-one (XII) instead of a polyamide. This reaction constitutes a new method for the synthesis of these heterocycles.     

Development of natural product (1 → 3)-β-D-glucan polymers as immune-stimulating pharmaceuticals

Glucan phosphate is a water-soluble, yeast-derived, (1 → 3)-β-D-glucopyranose polymer that has been demonstrated to be a potent immune stimulant. Glucan phosphate administration is associated with stimulation of immunity and a concomitant increase in resistance to a variety of experimentally induced disease states. Preclinical safety evaluation indicates that glucan phosphate does not induce mortality or significant toxicity over a wide dose range. Phase I clinical data indicate that glucan phosphate will ameliorate immunosuppression, stimulate immunity, decrease susceptibility to infection and alter ultimate outcome in trauma patients following laparotomy or thoracotomy. This work reviews the development, characterization, preclinal and clinical evaluation of glucan phosphate.     

The grafting of acrylamide onto poly(ε‐caprolactone) and poly(1,5‐dioxepan‐2‐one) using electron beam preirradiation. I. Influence of dose and Mohr's salt for the grafting onto poly(ε‐caprolactone)

Poly(ε‐caprolactone) films (TONE® 787) were irradiated by electron beam in air prior to grafting in aqueous solutions of acrylamide. The grafting kinetics and molecular weight of the grafted poly(acrylamide) chains were studied with irradiation doses between 2.5 and 20 Mrad and in the Mohr's salt concentration range of 0.0025–1 wt %. The grafting rate and yield were strongly dependent on the Mohr's salt concentration. By molecular weight analysis of grafted poly(acrylamide) chains, it was shown that the molecular weight is approximately proportional to the mass of the grafted PAAm. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 1643–1649, 1999     

Mass spectra of some (Z)-α-Phenyl-β-(2-thienyl)acrylonitriles

The mass spectra of some (Z)α-(4-R′-phenyl)-β-(2-thienyl-5-R)acrylonitriles (R = H, CH₃, Br; R′ = H, CH₃O, CH₃, Cl, NO₂) at 70 eV are reported. Mass spectra exhibit pronounced molecular ions. The compound's where R = H, and CH₃ are characterized by the occurrence of a strong [M - H]⁺ peak. Moreover, in all the compounds a m/z 177 peak occurs. In the compounds where R = H, [M - HS]* and [M - CHS]* ions are present except the nitroderivatives. Where R = CH₃, [M - HS]⁺ ion occurs.