Insights into the synthesis of lipopolysaccharide and antibiotics through the structures of two retaining glycosyltransferases from family GT4

Glycosyltransferases (GTs) catalyze the synthesis of the myriad glycoconjugates that are central to life. One of the largest families is GT4, which contains several enzymes of therapeutic significance, exemplified by WaaG and AviGT4. WaaG catalyses a key step in lipopolysaccharide synthesis, while AviGT4, produced by Streptomyces viridochromogenes, contributes to the synthesis of the antibiotic avilamycin A. Here we present the crystal structure of both WaaG and AviGT4. The two enzymes contain two "Rossmann-like" (beta/alpha/beta) domains characteristic of the GT-B fold. Both recognition of the donor substrate and the catalytic machinery is similar to other retaining GTs that display the GT-B fold. Structural information is discussed with respect to the evolution of GTs and the therapeutic significance of the two enzymes.     

Inositolphosphoglycan Mediators: An Effective Synthesis of the Conserved Linear GPI Anchor Structure*

An effective new preparative synthesis of the conserved linear pseudopentasaccharide structure of the GPI anchors and of the full GPI structure has been carried out that has permitted obtaining both molecules in sufficient quantities as to perform further structural and biologic studies. The synthesis involves a 3+2 block synthesis strategy in which a conveniently protected Man α(1→4) GlcN₃ α(1→6) myo‐Ins building block, previously used in the synthesis of inositolphosphoglycan (IPG) mediators, is glycosylated with a protected Man α(1→2) Man trichloroacetimidate.     

Total synthesis of the putative structure of the lupin alkaloid plumerinine

[reaction: see text]. A stereocontrolled synthesis of quinolizidine 1, the reported structure of plumerinine, has been accomplished in 10 steps from 4-methoxypyridine. The key step is a highly facial selective intramolecular [2 + 2] photocycloaddition of a 2,3-dihydro-4-pyridone. The reported spectral data for plumerinine did not match that of our synthetic 1.     

Strong templating effect of TEAOH in the hydrothermal genesis of the AlPO4-5 molecular sieve: Experimental and computational investigations

The hydrothermal genesis of AlPO₄-5, in the presence of four different organic templates, viz., methyldicyclohexylamine (MCHA), triethylamine (TEA), tripropylamine (TPA), and tetraethylammonium hydroxide (TEAOH), has been monitored by XRD. It is shown that TEAOH has the best templating ability to the formation of AlPO₄-5 structure under the different synthesis conditions considered in this study. Density functional calculations on periodic models of AlPO₄-5 indicate the strongest nonbonding interaction energy between the template and the framework in the case of TEAOH. Therefore, a new approach correlating the nonbonding interaction energy to the template ability to form a porous structure is proposed as a step toward a better understanding of the role of the organic template in the synthesis of porous molecular sieves.     

Total synthesis of the reputed structure of alcyonin and reassignment of its structure

Introduction of the C4 hydroxyl group by an epoxy ester rearrangement is a pivotal step in the first total synthesis of the purported structure of alcyonin. As the spectral data for diol acetate 3 do not match those reported for alcyonin, the structure of this marine diterpene must be revised. Reexamination of NMR spectra, MS data, and chemical transformations of natural alcyonin suggests that the structure of this marine metabolite is allylic peroxide 15.[structure: see text]     

Effect of Synthesis Conditions on the Formation of the CuCrAlO<Subscript>4</Subscript> Spinel Structure

The effect of synthesis conditions of mixed hydroxy compounds (coprecipitation mode, residence and aging times, precipitator nature) on the structural characteristics of CuCrAlO₄ spinels is studied. Evolution of the spinel structure during the solid-phase synthesis is analyzed.     

Direct chemical synthesis of the beta-D-mannans: the beta-(1-->2) and beta-(1-->4) series

The direct syntheses of a beta-(1-->2)-mannooctaose and of a beta-(1-->4)-mannohexaose are reported by means of 4,6-O-benzylidene-protected beta-mannosyl donors. The synthesis of the (1-->2)-mannan was achieved by means of the sulfoxide coupling protocol, whereas the (1-->4)-mannan was prepared using the analogous thioglycoside/sulfinamide methodology. In the synthesis of the (1-->4)-mannan, the glycosylation yields and stereoselectivities remain approximately constant with increasing chain length, whereas those for the (1-->2)-mannan consist of two groups with the formation of the tetra- and higher saccharides giving yields and selectivities consistently lower than those of the lower homologues. The decrease in yield after the trisaccharide in the (1-->2)-mannan synthesis is attributed to steric interference by the n-3 residue and is consistent with the collapsed, disordered structure predicted by early computational work. The consistently high yields and selectivities seen in the synthesis of the (1-->4)-mannan are congruent with the more open, ordered structure originally predicted for this polymer. The lack of order in the structure of the (1-->2)-mannan, as compared to the high degree of order in the (1-->4)-mannan, is also evident from a comparison of the NMR spectra of the two polymers and even from their physical nature: the (1-->2)-mannan is a gum and the (1-->4)-mannan is a high melting solid.     

Structure of an unsymmetrical isomer from the attempted synthesis of 1,8-dicyclooctatetraenylnaphthalene.

Attempted synthesis of 1,8-dicyclooctatetraenylnaphthalene (1) by the palladium(0)-catalyzed coupling of 1,8-dibromonaphthalene with cyclooctatetraenyltrimethylstannane afforded a single unsymmetrical isomer of 1 in 88% yield. Two-dimensional NMR methods and spectral synthesis were employed to assign the structure of the isomer (2). AM1 geometry-optimized structures of 2 and its isomers showed that the unexpected unsymmetrical structure of 2 results from the minimization of repulsive inter-ring H-H interactions. Compound 2 is postulated to arise via tandem [2 + 2] cycloaddition and 6 pi --> 4 pi + 2 sigma electrocyclization reactions of 1.     

Applications of Alkali Metal Hydroxide Hydrofluxes to the Synthesis of Single-Crystal Ternary Actinide Oxides

Hydrofluxes are hydrated salts with melting points well below that of the dehydrated salt and boiling points well above that of water, affording a reaction medium, in which mild temperatures and pressures can be accessed for the synthesis of materials. Herein, the use of alkali metal hydroxide hydrofluxes for the synthesis of single crystal α-Na₂NpO₄ is described, and the single crystal X-ray structure of α-Na₂NpO₄, along with its X-ray absorption spectra and vibrational spectra, is reported. The ability to synthesize complex oxides of the actinides, in particular, transuranium materials, under mild conditions will serve to advance our ability to explore the structure–property relationships of the f elements.     

Quantitative and physical evaluation of patchouli essential oils obtained from different sources of Pogostemon cablin

Patchouli essential oil can be obtained from fresh, dried and fermented plant material. It is a highly valuable product in the fragrance industry and its quality changes depending upon raw material age and oil storage. In this work, patchouli essential oils derived from different treatments have been subjected to GC-FID quantitative analysis using an internal standard (ISTD) method with response factors (RF). Samples were obtained from i) fresh plants; ii) hydrodistillation of one year mature and fermented plants; iii) hydrodistillation of one year mature plants; iv) commercial products from Indonesia and Malaysia. Linear Retention Indices (LRI) for both polar and non-polar GC-MS analyses were also measured as a tool for qualitative analysis towards a homologous series of C7-C30 n-alkanes. The results obtained confirmed that, in all samples, patchouli alcohol was the main volatile constituent, with higher amount in lab-scale produced oils, compared with commercial samples. Other major compounds, in lab oils and commercial samples respectively, were: delta-guaiene, alpha-guaiene, pogostol, seychellene and alpha-patchoulene. Another 36 compounds were also found.     

Synthesis of the chlorofusin cyclic peptide: assignment of the asparagine stereochemistry

An efficient synthesis of two diastereomers of the chlorofusin cyclic peptide bearing either the l-Asn3/d-Asn-4 or d-Asn3/l-Asn4 stereochemistry is detailed. Four key subunits were prepared, sequentially coupled, and cyclized to provide the two diastereomeric macrocycles. The absolute stereochemistry at the asparagine residues 3 and 4 was assigned as l and d, respectively, by correlating the NMR data of the two diastereomers with that reported for the natural product. [structure: see text]     

Synthesis of the core structure of the lipoteichoic acid of Streptococcus pneumoniae

Streptococcus pneumoniae LTA is a highly complex glycophospholipid that consists of nine carbohydrate residues: three glucose, two galactosamine and two 2‐acetamino‐4‐amino‐2,4,6‐trideoxygalactose (AATDgal) residues that are each differently linked, one ribitol and one diacylated glycerol (DAG) residue. Suitable building blocks for the glucose and the AATDgal residues were designed and their synthesis is described in this paper. These building blocks permitted the successful synthesis of the core structure Glcβ(1‐3)AATDgalβ(1‐3)Glcα(1‐O)DAG in a suitably protected form for further chain extension ( 1 b , 1 c ) and as unprotected glycolipid ( 1 a ) that was employed in biological studies. These studies revealed that 1 a as well as 1 lead to interleukin‐8 release, however not via TLR2 or TLR4 as receptor.     

Synthesis,structure, spectral and coordination properties of a crown ether derivative of 1,3-indandione. A new structural evidence for the versatile reactivity of 2-acetyl-1,3-indandione

The current study describes the synthesis of a new 1,3-indandione derivative with conjugated N-phenylaza-15-crown-5 moiety (4). The crystal structure of compound 4 was solved and its optical properties were studied in various solvents and in presence of alkaline and alkaline-earth metal ions. Quantum chemical (DFT) methods were employed to describe the structure and the optical properties of the studied compound and its complexes. The obtained results indicated that the synthesis of compound 4 using acid-catalyzed aldol reaction between 2-acetyl-1,3-indandione and the corresponding aldehyde is accompanied with an unexpected deacetylation step. In this way, the N-phenylaza-15-crown-5 moiety is directly conjugated with the 1,3-indandione fragment, known as a very strong electron acceptor. Therefore, the absorption spectra of 4 are only slightly influenced by complexation with Ba²⁺ and Sr²⁺ ions.     

Synthesis of Two Metabolites of the Antiarrythmicum Amiodarone

The metabolism of the potent antiarrythmic drug amiodarone (AMI; 1 ) has yet not been fully investigated. Recently, in vitro experiments revealed that in rabbit‐liver microsomes, AMI ( 1 ) and its main metabolite MDEA ( 2 ) were biotransformed to the hydroxylated derivatives 3′‐OH‐AMI ( 3 ) and 3′‐OH‐MDEA ( 4 ), respectively. To establish the chemical structure of 3 and 4 , we developed a total synthesis of these two metabolites of AMI ( 1 ). ¹H‐ and ¹³C‐NMR Signal assignment from HSQC and HMBC 2D NMR data of synthesized 4 showed that the proposed structure of metabolite 4 is correct. Even the structure of 3 was found to be correct by comparing its HPLC/MS‐MS/MS with the data described earlier.     

Synthesis of α-eucryptite by the sol-gel method

New method is reported for synthesis of α-eucryptite LiAlSiO₄ whose framwork structure has voids that enable its doping with lanthanides. The optical parameters of this orthosilicate and results of introduction of europium ions into its composition to create a phosphor were studied.     

2-(4-alkylamido-2-hydroxyphenyl)benz-X-azoles as intermediates for the synthesis of dyes

Nineteen substituted 2-phenylbenz-X-azoles, which are intermediates for the synthesis of dyes, were prepared from p-aminosalicylic acid (PAS). Substituents in the phenyl ring are 2′-hydroxy and/or 4′-amino and 4′-alkylamido with alkyl chains ranging from C₁ to C₁₅. The preferred route of the synthesis is discussed. The melting points and the R_f values are correlated with the structure. An extensive discussion of the electronic absorption spectra, involving other compounds with the same general structure, is reported.     

Intermediates for the synthesis of tetracyclic indole alkaloids. Synthesis of 4-aminotetrahydrocarbazole derivatives

An efficient method for the synthesis of 4-aminotetrahydrocarbazole derivatives from 2,3-dihydrospiro-[1H-carbazole-1,2′-(1,3)-dithiolan]-4-(9H)-one 1 is described. The structure of compound 6 has been confirmed by X-ray structure analysis.     

纳米四氧化三锰温和水相合成及其电容性能

采用温和水相合成法制备出纳米Mn3O4,采用X射线衍射（XRD）、电子能谱（XPS）及透射电子显微镜（TEM）等技术手段对其结构、组成与形貌进行了研究分析;并利用循环伏安（CV）及充放电等电化学测试研究了纳米Mn3O4的电容性能。 结果表明,本实验所制备的纳米Mn3O4为四方相γ-Mn3O4,其粒径大小为40~60 nm;该材料具有良好的电容性能,其比电容值可达270 F/g,且经1000次循环后,其比电容值可达原来的85%。     

Synthesis and molecular structure of ethyl [N-tosyl-(R)-prolyloxy]-2(S)-[4-cyano-8,8-ethylenedioxy-5-oxo-5,6,7,8-tetrahydroindolizin-3-yl] acetate, a key intermediate in the total synthesis of (20S)-camptothecins

The synthesis of optically active [N-tosyl-(R)-prolyloxy]-2(S)-[4-cyano-8,8-ethylenedioxy-5-oxo-5,6,7,8-tetrahydroindolizin-3-yl] acetate (4a), a key intermediate for the total asymmetric synthesis of 20(S)-camptothecin anticancer drugs, is described. Its structure was characterized by 2D-NMR techniques and the absolute configuration was further confirmed for the first time by X-ray crystal structure analysis.     

Total synthesis of the formamicin aglycon,formamicinone

[structure: see text] The total synthesis of formamicinone (2), the aglycone of formamicin (1), has been accomplished via the late-stage Suzuki cross-coupling of fragments 5 and 6, the macrolactonization of seco ester 14, and the Mukaiyama aldol reaction of aldehyde 3 and methyl ketone 4. An efficient and highly stereoselective second generation synthesis of vinyl iodide 6 is also described.