Temperature dependence of the cristobalite α-β inversion

The cristobalite - inversion has been studied using DSC on cristobalites produced by firing high purity quartz with and without addition of a mineraliser. If no mineraliser was used, the inversion temperatures and hysteresis on heating and cooling increased with firing temperature. Firing time had little or no effect on inversion temperature. When a mineraliser was used, the same general trend was observed with increases in firing time at low temperatures leading to splitting of the inversion peak. The amount of mineraliser added had little effect. Tridymite inversions were also observed. The results are explained in terms of the degree of order of the cristobalite structure.We are grateful for the award of an S.E.R.C. CASE award in conjunction with Specialist Refractory Services to SJS. Helpful discussions have been held with Mr. D. W. Bailey and Dr. P. Watkins.     

Study of the enantioselectivity of the CAL-B-catalysed transesterification of α-substituted α-propylmethanols and α-substituted benzyl alcohols

A study of the enantioselectivity exhibited by the lipase B from Candida antarctica in the transesterification of different α-substituted α-propylmethanols with vinyl acetate is shown. The best results are obtained when the large-sized (L) substituent of the alcohol is either a phenyl group or more especially a cyclohexyl group, although the reaction rates are lower than when linear or slightly branched groups are present. It is also found that ramification at the β-position of the L substituent has a deleterious effect on both lipase activity and enantioselectivity. Moreover, some α-substituted benzyl alcohols bearing medium-sized (M) substituents larger than an ethyl and smaller than a propyl group are resolved by means of this methodology with moderate-good enantioselectivities (E=46–57) and similar reaction rates.     

1-(1-Alkenyl)benzotriazoles: Novel α-Hydroxyacyl Anion Equivalents for the Synthesis of α-Hydroxy Ketones

α-Lithiated 1-(1-alkenyl)benzotriazoles, generated from the reactions of 1-(1-alkenyl)benzotriazoles with n-BuLi, react with a variety of electrophiles to afford α-substituted 1-(1-alkenyl)benzotriazoles which undergo epoxidation with m-CPBA followed by hydrolysis to give α-hydroxy ketones in good yields. Thus, 1-(1-alkenyl)benzotriazoles behave as α-hydroxyacyl anion equivalents.     

Study of the capillary electrophoresis profile of intact α-1-acid glycoprotein isoforms as a biomarker of atherothrombosis

α-1-Acid glycoprotein (AGP) is a serum glycoprotein that presents several isoforms. Changes in the isoforms of AGP have been related to different pathological states including cardiovascular diseases (CVDs) such as acute myocardial infarction. However, to our knowledge, the role of variations of AGP isoforms as a potential biomarker of atherothrombosis has not been addressed. In this work, a preliminary study about differences in the capillary zone electrophoresis (CZE) profile of intact (non-hydrolyzed) AGP isoforms between healthy individuals and patients with atherothrombosis, specifically abdominal aortic aneurysm (AAA) and carotid atherosclerosis (CTA), has been performed. Biological samples (plasmas and sera) were analyzed by CZE after immunoaffinity chromatography purification. Up to 13 peaks corresponding to groups of isoforms of intact AGP from plasma samples were detected by CZE-UV. Electrophoretic profiles were aligned, peaks assigned, and linear discriminant analysis (LDA) of percentage of the corrected areas of AGP peaks was employed to discriminate and classify the CZE profiles of AGP samples. LDA enabled to accomplish 92.9% of correct classification of the AGP samples when the three groups of samples were considered. Besides, the LDA model showed high predictive power in the groups healthy vs. sick, healthy vs. AAA, and healthy vs. CTA. The described method was a successful approach to study the potential of AGP isoforms profile as a biomarker of atherothrombosis. To the best of our knowledge this has been the first time that a possible role of the CZE profile of intact AGP isoforms as a biomarker of vascular diseases has been demonstrated.     

The Preparation of α-Phosphonovinylzirconocenes and their Application in the Stereospecific Synthesis of α-Halo-1 -alkenylphosphonates

Hydrozirconation of 1-alkylnylphosphonates gives the organozirconium(Ⅳ) complexes 2 in syn-addition way. Complexs 2 was trapped with NCS, NBS or I2 to afford stereodifined α-halo-1-alkenylphosphonates in moderate to high yields.     

Regio- and Diastereoselectivity in the Thiomethylation of α-(1-Hydroxyalkyl)acrylate Derivatives

The regio-and diastereoselectivity of reactions of selected α-(1-hydroxyalkyl)acrylate derivatives with sodium methanethiolate have been investigated. The hydroxy compounds typically undergo conjugate addition with up to 66% d.e., while the acetoxy and bromo analogues favour S_N' and S_N reactions, respectively.     

The Application of the Trichloroacetimidate Method to the Synthesis of α-D-Gluco- and α-D-Galactopyranosides

Abstract

The trichloroacetimidate method has been applied to the construction of α-d-galacto- and α-d-glucopyranosides. The readily available β-trichloroacetimidates of 2,3,4,6-tetra-O-benzyl-d-galacto- and glucopyranose (1-β and 3-β, respectively) have been employed in glycosidations with several monosaccharides (either A, B, C or D) under varying experimental conditions. With the galactose derivative 1-β as a donor and each of the monosaccharides A-D as acceptors, the corresponding disaccharides 1A-1D, were obtained in high yield and with good α-stereoselectivity when employing diethyl ether as solvent and either trimethylsilyl- or tert-butyldimethylsilyl trifluoro-methane sulphonate as catalyst. Glycosidations with the glucose derivative 3-β, as donor, and with the monosaccharide acceptors A, B or D, gave the corresponding disaccharides 3A, 3B and 3D, in high yield but with somewhat lower α-diastereoselectivity than observed with the galactose derivative 1-β. The stereochemical outcome of the reactions is rationalised in terms of possible reaction mechanisms.     

Synthesis of (+)- and (−)-Tetrabenazine from the Resolution of α-Dihydrotetrabenazine

Abstract

Tetrabenazine (1) was reduced with NaBH₄ to α-dihydrotetrabenazine (2) and then resolved with di-p-toluoyl-L-tartrate and di-p-toluoyl-D-tartrate to subsequently give (+)- and (?)-α-dihydrotetrabenazine. The enantiomers were oxidized under Swern conditions to prepare samples of (+)-tetrabenazine and (?)-tetrabenazine. The samples were optically pure by chiral HPLC analysis.     

Total synthesis of α-1C-galactosylceramide, an immunostimulatory C-glycosphingolipid, and confirmation of the stereochemistry in the first-generation synthesis

A nonisosteric α-C-glycoside analogue of KRN7000 (α-1C-GalCer, 1) was reported to induce a selective type of cytokine release in human invariant natural killer cells in vitro. We report here a very concise synthetic route to 1 and its analogue 1'. The key steps include olefin cross-metathesis, Sharpless asymmetric epoxidation, and epoxide opening by NaN(3)/NH(4)Cl. Inversion of configuration at the amide-bearing carbon in the phytosphingosine backbone constructed by epoxide opening in our previous synthesis of 1 was verified, indicating that remote group participation is not involved during the epoxide-opening reaction.     

Advances in the synthesis of homochiral (-)-1-azafagomine and (+)-5-epi-1-azafagomine. 1-N-phenyl carboxamide derivatives of both enantiomers of 1-azafagomine: Leads for the synthesis of active α-glycosidase inhibitors

A new expeditious preparation of homochiral (-)-1-azafagomine and (+)-5-epi-1-azafagomine has been devised. Stoodley's diastereoselective cycloaddition of dienes bearing a 2,3,4,6-tetraacetyl glucosyl chiral auxiliary to 4-phenyl-1,2,4-triazole-3,5-dione was merged with Bols's protocol for functionalizing alkenes into molecules bearing a glucosyl framework. Homochiral (+)-5-epi-1-azafagomine was synthetized for the first time. Partial reductive cleavage of the phenyltriazolidinone moiety afforded new homochiral 1-N-phenyl carboxamide derivatives of 1-azafagomine. Both enantiomers of these derivatives were synthetized and tested, displaying a very good enzymatic inhibition toward baker's yeast α-glucosidase. The molecular recognition mechanism of the 1-N-phenyl carboxamide derivative of 1-azafagomine by α-glucosidase from baker's yeast was studied by molecular modeling. The efficient packing of the aromatic ring of the 1-N-phenyl carboxamide moiety into a hydrophobic subsite (pocket) in the enzyme's active site seems to be responsible for the improved binding affinity in relation to underivatized (-)-1-azafagomine and (+)-1-azafagomine.     

Restricted variation in the glycosylation of human α1-acid glycoprotein

Summary The glycosylation patterns of multiglycosylated proteins reflect both the cellular control of glycosyl transferase activity and the local control of the transfer event. Little information is available concerning these mechanisms. Changes in glycosylation occur in the disease state and provide a convenient way of examining the control mechanism(s) operating at individual glycosylation sites. Chromatographic methods have been applied to the human orosomucoid (OMD) isolated from seventeen different pathologies. Based on the distribution of the glycans at the individual sites it is clear that the major protein-glycan interactions that restrict glycosylation in normal OMD remain intact in the disease state in the presence of changing glycosyl transferase activity.     

Enzymatic α(1→2)-l-fucosylation: investigation of the specificity of the α(1→2)-l-galactosyltransferase from Helix pomatia

The α(1→2)-l-galactosyltransferase from Helix pomatia transfers an l-fucosyl residue from GDP-l-Fucose to a terminal, non-reducing d-galactopyranosyl moiety of an oligosaccharide. The extent of the enzyme's specificity towards the stereochemistry at the d-galactopyranosyl anomeric centre, the site of interglycosidic linkage and the nature of the subterminal oligosaccharide residue has been investigated using HPAEC-PAD and MALDI-TOF technology. This α(1→2)-l-galactosyltransferase is specific for d-galactopyranosyl β-linkages, independent of the site of the interglycosidic linkage and aglycone configuration and with limited specificity for the nature of the subterminal sugar residue.     

Synthesis and Characterization of the Crystalline Methyl α-Glycoside of the Repeating Unit of the O-Polysaccharide of Vibrio Cholerae O:1

Abstract

There are more than eighty serotypes of Vibrio cholerae, all causing disease with symptoms of Asian cholera. Systematic prevention of cholera by immunization has not yet been achieved because of a lack of a protective vaccine. Vibrio cholerae 0:1 Gramnegative bacteria occur as two immunologically distinct strains: Ogawa and Tnaba. The lipopolysaccharide (LPS) of both strains seem to contain the same 0-polysaccharide antigen consisting^3,4 of (1+2)-a-linked 4-amino-4,6-dideoxy-a-D-mannopyranosyl residues the amino groups of which are acylated with 3-deoxy-L-glycero-tetronic acid. Although the chemical structure of the 0-polysaccharides has been known5 since 1979, the synthesis of its monomeric repeating unit was reported only in 1988.     

Claisen rearrangement of allylic α-isocyano-esters—regioselective allylation of α-isocyanoesters at the α-carbon

A regioselective allylation of α-isocyanoesters at the α-carbon was achieved by the Claisen rearrangement of allylic α-isocyanoesters via the corresponding silyl ketene acetals in situ generated.     

The kinetics of the polymorphic transition of the α-form of 2,4,6,8,10,12-hexanitrohexaazaisowurtzitane

The α → γ polymorphic transition in hexanitrohexaazaisowurtzitane was studied by optical microscopy, calorimetry, IR spectroscopy, thermogravimetry, and X-ray diffraction. The thermal effect of the transition was determined. The kinetics of the process is complex because of the relation between structural rearrangement and transition with the removal of water stabilizing the structure of the α polymorph. Depending on the morphological characteristics of the initial sample, the polymorphic transition can follow a frontal-heterogeneous mechanism (single crystal → polycrystalline aggregate) or a quasi-homogeneous mechanism (single crystal → single crystal).     

Features of the Tautomerism of Some α-Substituted Pyridines

The AM1 quantum-chemical semi-empirical method was used to calculate the values of the enthalpy of activation (H^#), the heats of reaction (H), and the tautomeric equilibrium constants (K_T) for several -substituted pyridines. It was found that the keto-enol tautomeric conversion in -pyridone occurs more readily than the amino-imino conversion in 2-aminopyridine but in 2-methylpyridine the tautomeric equilibrium does not exist at all.     

Influence of α-methyl substitution of proline-based organocatalysts on the asymmetric α-oxidation of aldehydes

The direct asymmetric organocatalytic α-oxidation of aldehydes using trans-2-(p-methylphenylsulfonyl)-3-phenyloxaziridine is reported. This method affords the S isomer of α-hydroxy aldehydes, thereby complementing the selectivity for the R isomer observed using the two-step nitrosobenzene method. Use of α-methylproline and α-methylproline tetrazole significantly increases the enantioselectivity observed for the α-oxidation of aldehydes compared to analogous unsubstituted organocatalysts.     

On the structure of α-metallo benzylselenides

Decreasing electron attracting ability of the para substituent X leads to an upfield shift of the ¹¹Se signal of para substituted benzylselenides. Reverse results are however observed when the measurements are performed on the corresponding para substituted metallo benzylselenides.