Crystal and molecular structures of 6-O-acetyl-2,3,4-trideoxy-alpha-DL-glycero-hex-2-enopyranose and 3-O-(6-O-acetyl-2,3,4-trideoxy-alpha-L-glycero-hex-2-enopyranosyl++ +)-1,2 ;5,6-di-O-isopropylidene-alpha-D-glucofuranose

6-O-acetyl-2,3,4-trideoxy-alpha-DL-glycero-hex-2-enopyranose (1) and 3-O-(6-O-acetyl-2,3,4-trideoxy-alpha-L-glycero-hex-2-enopyranosyl) -1,2;5,6-di-O-isopropylidene-alpha-D-glucofuranose (2) have been investigated by X-ray diffraction methods. Compound 1 crystallises in the monoclinic system, space group P21/a, with cell constants a = 21.123(5), b = 4.439(2), c = 10.085(2) A, and beta = 110.22(2) degrees. Compound 2 crystallises in the orthorhombic system, space group P212121, with cell constants a = 22.110(6), b = 11.651(4), and c = 8.658(3) A. The intensity data were collected in a four-circle automatic diffractometer, with 1488 reflections for 1, and 2151 for 2. The structures were solved by direct methods. The atomic parameters were refined in an anisotropic mode by the full-matrix, least-squares procedure against 1065 and 1884 observed reflections for 1 and 2, respectively, giving R = 0.046 for each compound. The 2-enopyranose rings in 1 and 2 adopt half-chair conformations (H), and that in 2 is markedly deformed. The 1,2-dioxolane ring in 2 has an envelope (E) conformation, whereas the 5,6-dioxolane ring is dynamically disordered and can be represented by a conformational hybrid (E + P). The alpha-D-glucofuranose ring in 2 has a twist conformation (T). The glycoside bond in 2 is characterized by phi and psi torsion angles of 47(2) degrees and 32(2) degrees, respectively.     

Synthesis of a fully protected derivative of O-(N-acetyl-alpha-D-neuraminyl)-(2----3)-O-beta-D-galactopyranosyl-(1- ---3)-O- [(N-acetyl-alpha-D-neuraminyl)-(2----6)]-O-(2-acetamido-2-deoxy-alpha- D-galactopyranosyl)-(1----3)-L-serine

N-(Benzyloxycarbonyl)-O-[methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galact o-2- nonulopyranosyl)onate]-(2----3)-O-(2,4,6-tri-O-acetyl-beta-D - galactopyranosyl)-(1----3)-O-[methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galact o-2- nonulopyranosyl)onate-(2----6)]-O-(2-acetamido-4-O-acetyl-2- deoxy-alpha-D- galactopyranosyl)-(1----3)-L-serine benzyl ester was synthesized by using O-[methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5- di-deoxy-D-glycero-alpha-D-galacto-2-nonulopyranosyl)onate]- (2----3)-O-(2,4,6- tri-O-acetyl-beta-D-galactopyranosyl)-(1----3)-O-[methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galact o-2- nonulopyranosyl)onate-(2----6)]-4-O-acetyl-2-azido-2-deoxy-a lpha- and -beta-D-galactopyranosyl trichloroacetimidate as a key glycotetraosyl donor which, upon reaction with N-(benzyloxycarbonyl)-L-serine benzyl ester, afforded a 44% yield of a mixture of the alpha- and beta-glycosides in the ratio of 2:5.     

Thermotropic phase properties of 1,2-di-O-tetradecyl-3-O-(3-O-methyl- beta-D-glucopyranosyl)-sn-glycerol.

The hydration properties and the phase structure of 1,2-di-O-tetradecyl-3-O(3-O-methyl-beta-D-glucopyranosyl)-sn-glycerol (3-O-Me-beta-D-GlcDAIG) in water have been studied via differential scanning calorimetry, 1H-NMR and 2H-NMR spectroscopy, and x-ray diffraction. Results indicate that this lipid forms a crystalline (Lc) phase up to temperatures of 60-70 degrees C, where a transition through a metastable reversed hexagonal (Hll) phase to a reversed micellar solution (L2) phase occurs. Experiments were carried out at water concentrations in a range from 0 to 35 wt%, which indicate that all phases are poorly hydrated, taking up < 5 mol water/mol lipid. The absence of a lamellar liquid crystalline (L alpha) phase and the low levels of hydration measured in the discernible phases suggest that the methylation of the saccharide moiety alters the hydrogen bonding properties of the headgroup in such a way that the 3-O-Me-beta-D-GlcDAIG headgroup cannot achieve the same level of hydration as the unmethylated form. Thus, in spite of the small increase in steric bulk resulting from methylation, there is an increase in the tendency of 3-O-Me-beta-D-GlcDAIG to form nonlamellar structures. A similar phase behavior has previously been observed for the Acholeplasma laidlawii A membrane lipid 1,2-diacyl-3-O-(6-O-acyl-alpha-D-glucopyranosyl)-sn-glycerol in water (Lindblom et al. 1993. J. Biol. Chem. 268:16198-16207). The phase behavior of the two lipids suggests that hydrophobic substitution of a hydroxyl group in the sugar ring of the glucopyranosylglycerols has a very strong effect on their physicochemical properties, i.e., headgroup hydration and the formation of different lipid aggregate structures.     

Synthetic mucin fragments: methyl 3-O-(2-acetamido-2-deoxy-beta-D-galactopyranosyl-beta-D- 3-O-(2-acetamido-2-deoxy-3-O-beta-D-galactopyranosyl- beta-D-glucopyranosyl)-beta-D-galactoyranoside. pyranosyl)-beta-D-galactopyranoside

Methyl 2,4,6-tri-O-benzyl-beta-D-galactopyranoside (5) was obtained crystalline by way of its 3-O-allyl derivative, which was in turn obtained by ring-opening of a presumed 3,4-O-stannylene derivative of methyl beta-D-galactopyranoside, followed by benzylation. Condensation of 5 with 2-methyl-(2-acetamido-3,4,6-tri-O-acetyl-1,2-dideoxy-beta-D-glucopyra no)-[2,1-d]-2-oxazoline in 1,2-dichloroethane in the presence of p-toluenesulfonic acid afforded the disaccharide derivative methyl 3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl)-2, 4,6-tri-O-benzyl-beta-D-galactopyranoside (6) Deacetylation of 6 in methanolic sodium methoxide afforded the disaccharide derivative 7, which was acetalated with alpha, alpha-dimethoxytoluene to afford the 4',6'-O-benzylidene acetal (10). Catalytic hydrogenolysis of the benzyl groups of 7 afforded the title disaccharide 8. Glycosylation of 10 with 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide in 1:1 benzene-nitromethane in the presence of mercuric cyanide gave the fully protected trisaccharide derivative 12. Systematic removal of the protecting groups of 12 then furnished the title trisaccharide 14. The structures of 5, 8, and 14 were all confirmed by 13C-n.m.r. spectroscopy. The 13C-n.m.r. chemical shifts for methyl alpha- and beta-D-galactopyranoside, and also those of their 3-O-allyl derivatives, are recorded, for the sake of comparison, in conjunction with those of compound 5.     

2-O-(beta-D-glucuronyl)-7-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-L-glycero-D-manno-heptose: a constituent of the Bordetella pertussis endotoxin.

The presence of bound D-glucuronic acid in the endotoxin of Bordetella pertussis was demonstrated. The branched chain trisaccharide named in the title was isolated after hydrolysis of the endotoxin with 3 M HCl for 2 h at 100 degrees C. Its structure was established by chemical and enzymic degradation.     

Synthesis and antibacterial activities of a novel alkylide: 3-O-(3-aryl-2-propargyl) and 3-O-(3-aryl-2-propenyl)clarithromycin derivatives

A series of novel 3-O-(3-aryl-E-2-propenyl)clarithromycin derivatives 8 and 3-O-(3-aryl-2-propargyl)clarithromycin derivatives 11 were designed, synthesized, and evaluated for their in vitro antibacterial activities. Compared with 8c and 11c (Ar was 5-pyrimidyl), 3-O-(3-(5′-pyrimidyl)-Z-1-propenyl) counterpart 6c displayed 4- to 64-fold more potent activities against erythromycin-susceptible Staphylococcus aureus and Streptococcus pneumoniae. Moreover, the activities of 6c, 8c, and 11c against erythromycin-resistant S. aureus and S. pneumoniae were in general 4-fold higher than those of the reference compound, clarithromycin and azithromycin.     

Synthesis of branched-chain sugar derivatives from 1,2;5,6-di-O-isopropylidene-alpha-D-ribo-hexofuranos-3-ulose and 1,2;4,5-di-O-isopropylidene-beta-D-erythro-2-hexulopyranos-3-ulose

A facile method for the formation of branched-chain sugar derivatives is described involving the reaction of lithium dianions and carboxylic acids with keto-sugar derivatives. Acetic, propanoic, phenylacetic, 3,3-dimethylacrylic, crotonic and sorbic acids were the acids used for the preparation of the lithium dianions, and glucose and fructose were used for preparation of the keto derivatives.     

Synthesis of 1,2-dipalmitoyloxypropyl-3-(2-trimethylammoniumethyl)phosphinate

The total synthesis of 1,2-dipalmitoyloxypropyl-3-(2-trimethylammoniumethyl)phosphinate, the phosphinate analog of phosphatidylcholine, is described. The phosphinate analog has been essentially prepared by an Arbusov type reaction between 1,2-dipalmitoyl-sn-glycerolbromohydrin and 2-bromoethyl phosphonic acid dimethyl ester for 48 h at 170°C, followed by removal of the methyl ester with sodium iodide and reaction with aqueous trimethylamine to yield the final product. The phosphinate analog of phosphatidylcholine was characterized by elemental analysis, thin-layer chromatography (TLC), IR spectroscopy and phosphonophosphorus determinations.     

Synthesis of methyl 2,4-di-O-methyl-3-O-(2-O-methyl-alpha-L-rhamnopyranosyl)-alpha-L- rhamnopyranoside and methyl 2,4-di-O-methyl-3-O-[2-O-methyl-3-O-(2-O-methyl-alpha-L-fucopyranosyl)- alpha-L-rhamnopyranosyl]-alpha-L-rhamnopyranoside: di- and tri-saccharide segments of a phenolic glycolipid of Mycobacterium kansasii.

Syntheses of the title glycosides are described. The critical O-glycosylations were carried out in the presence of boron trifluoride etherate with a high degree of alpha-selectivity.     

Synthesis of 2,6-di(acylamino)-2,6-dideoxy-3-O-(d-2-propanoyl-l-alanyl-d-isoglutamine)-d-glucopyranoses

Five 2,6-di(acylamino)-2,6-dideoxy-3-O-(d-2-propanoyl-l-alanyl-d-isoglutamine)-d-glucopyranoses (lipophilic, muramoyl dipeptide analogs) were synthesized from benzyl 2-(benzyloxycarbonylamino)-3-O-(d-1-carboxyethyl)-2-deoxy-5,6-O-isopropylidene-β-dglucopyranoside (1). Methanesulfonylation of 3, derived from the methyl ester of 1 by O-deisopropylidenation, gave the 6-methanesulfonate (4). (Tetrahydropyran-2-yl)ation of 4 gave benzyl 2-(benzyloxycarbonylamino)-2-deoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-6-O-(methylsulfonyl)-5-O-(tetrahydropyran-2-yl)-β-d- glucofuranoside, which was treated with sodium azide to give the corresponding 6-azido derivative (6). Condensation of benzyl 6-amino-2-(benzyloxycarbonyl-amino)-2,6-dideoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-5-O-(tetrahydropyran-2-yl)-β-d-glucofuranoside, derived from 6 by reduction, with the activated esters of octanoic, hexadecanoic, and eicosanoic acid gave the corresponding 6-N-fatty acyl derivatives (8–10). Coupling of the 2-amino derivatives, obtained from compounds 8, 9, and 10 by catalytic reduction, with the activated esters of the fatty acids, gave the 2,6-(diacylamino)-2,6-dideoxy derivatives (11–15). Condensation of the acids, formed from 11–15 by de-esterification, with the benzyl ester of l-alanyl-d-isoglutamine, and subsequent hydrolysis, afforded benzyl 2,6-di(acylamino)-2,6-dideoxy-3-O-(d-2-propanoyl-l-alanyl-d-isoglutamine benzyl ester)-β-d-glucofuranosides. Hydrogenation of the dipeptide derivatives thus obtained gave the five lipophilic analogs of 6-amino-6-deoxymuramoyl dipeptide, respectively, in good yields.     

Coordination chemistry of the heterotopic 1,2-phenylenebis(thio)diacetic acid ligand: Rhodium(I), palladium(II) and nickel(II) complexes

Starting from the heterotopic multidentate ligand 1,2-phenylenebis(thio)diacetic acid (1), cis-rac-[PdCl₂{1,2-(HOOCCH₂S)₂C₆H₄-κ²S,S′}] (2), cis-rac-[Rh{1,2-(HOOCCH₂S)₂C₆H₄-κ²S,S′}(cod)]BF₄ (3) and cis-rac-[Ni{1,2-(OOCCH₂S)₂C₆H₄-κ⁴O,O′S,S′}{cis-(C₃H₄N₂)}₂] (4) were prepared and characterised by X-ray diffraction and conventional spectroscopic techniques. Compounds 1-4 show extensive hydrogen-bonded networks (XH?O, X = O, N) in the solid state.     

Water-soluble 3-O-(2-methoxyethyl)cellulose: synthesis and characterization

The synthesis of novel 3-O-(2-methoxyethyl)cellulose via 2,6-di-O-thexyldimethylsilyl ethers was successfully carried out. Treatments of 3-O-(2-methoxyethyl)-2,6-di-O-thexyldimethylsilylcellulose with tetrabutylammonium fluoride trihydrate led to a complete removal of the protecting groups. Structure characterization carried out by means of 1D and 2D NMR spectroscopy proves a high regioselectivity. The novel cellulose ether is soluble in dimethyl sulfoxide, N,N-dimethylacetamide, N-methylpyrrolidone, and water. Size-exclusion chromatography revealed a distinct aggregation behavior in water.     

Synthesis and proaggregatory activity of 1-O-(2-methyloctadecyl)-2-O-acetyl-rac-glycero-3-phosphocholine.

Racemic 1-O-(2-methyloctadecyl)-2-O-acetyl-glycero-3-phosphocholine, a branched chain PAF species, was prepared by chemical synthesis and investigated for biological activity on human blood platelets in vitro. The synthesis started from 2-O-benzylglycerol and 2-methyloctadecyl-1-methyl sulfonate and was accomplished in five reaction steps. A comparison with 'octadecyl-rich' PAF showed that the PAF species described here exerts a 22-fold weaker proaggregatory activity. Based on [3H]PAF-binding studies, an obstruction of PAF-binding or the signal transduction by the branched alkyl chain in C-1 position of the glycerol backbone is suggested.     

Synthesis and some properties of constrained short-chain phosphatidylcholine analogues: (+)- and (-)-(1,3/2)-1-O-(phosphocholine)2,3-O- dihexanoylcyclopentane-1,2,3-triol

Reported herein is the synthesis of (+)- and (-)-(1,3/2)-1-O-(phosphocholine)-2,3-O-dihexanoylcyclopentane-1,2, 3-triol. These are the enantiomers of a contrained analogue of dihexanoylphosphatidylcholine in which the glycerol backbone is replaced by all-trans cyclopentane-1,2,3-triol. Evidence is presented to demonstrate that the (-)-enantiomer is a substrate for phospholipase A2 (PLA2) (Crotalus atrox) while the (+)-enantiomer is not. This strict enantiomeric (and positional) specificity was exploited in conjunction with a novel application of DEAE-cellulose column chromatography, to achieve racemic resolution with an excellent yield. The constrained backbone geometry, and the experimentally accessible critical micellar concentration (CMC) of these analogues should render them useful probes for assessing the contribution of substrate conformation and flexibility to the catalytic efficiency of PLA2.