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Dans cet ouvrage imposant, introduit par une élégante Prefazione par Pietro Beltrami (p. XIII-XV), Hélène Carles propose une étude très fine et approfondie des lexèmes vernaculaires qu’elle a dégagés grâce au dépouillement des quelque 5 000 chartes en latin composant la collection Chartes originales antérieures à 1121 conservées en France, éditée et mise en ligne en 2008 par l’Atelier de recherche sur les textes médiévaux (Artem). Le butin ainsi amassé s’élève, après l’indispensable tri, à 51...

À quelques années de distance, il nous est bien agréable de nous remémorer l'ambiance festive dans laquelle se déroula, en mai 2004, le symposium de clôture de la Chaire Francqui au titre étranger, dont Alberto Varvaro fut le lauréat en 2003-2004. Venus de Belgique et d'ailleurs, les amis, les élèves anciens et récents de ce maître de la philologie romane actuelle, étaient présents pour célébrer la conclusion heureuse de la « Class of excellence » dont Monsieur Varvaro nous avait fait le cade...

1. Introduzione 1.1. II ms. Paris, BnF, fonds français 12598 Il codice 12598 del Fonds Français della Bibliothèque nationale de France è un manoscritto cartaceo, di 311 carte, su due colonne, trascritto probabilmente nel XVIII secolo sulla base di un modello del XV secolo, come lascia credere la grafia arcaizzante. Noto con il titolo di Neuf Preux o di Histoire des neuf preux princes et seigneurs, esso contiene, in successione, le biografie d’Ettore, Alessandro, Giulio Cesare, Giosué, Davide,...

L’article propose quatre critères permettant d’organiser les phénomènes à traiter afin de mieux articuler les relations entre la partie syntaxique et les autres sections de l’introduction : traits relatifs aux choix d’édition ; traits pouvant apporter des informations sur l’origine géographique du manuscrit, de son modèle ou de l’œuvre originale ; faits syntaxiques pouvant poser des problèmes de compréhension ; traits pouvant contribuer à définir les constructions préférées et caractéristiques d’un auteur ou d’un texte.

This book combines the contributions of many of the major players in this research field, and covers the synthesis of sugar-, base-, and backbone-modified nucleic acids, their structural characteristics studied by X-ray crystallography, and NMR in solution as well as their chemical and biological properties.

Cette étude analyse le passage de la Chanson de Roland du vers à la prose et propose une typologie des adaptations imposées à la matière rolandienne par les « prosateurs » médiévaux., This study focuses on the different translations of the Song of Roland from verse to prose and proposes a typology of the principles governing the adaptation of the Roland material by medieval « prosifiers ».

Stereochemistry is an important facet of chemistry. The study of stereochemical problems spans the entire range of organic, inorganic, biological, physical and supramolecular chemistries. Stereochemistry includes methods for determining and describing these relationships; the effect on the physical or biological properties these relationships impart upon the molecules in question, and the manner in which these relationships influence the reactivity of the molecules in question (dynamic stereochemistry). This book provides new research from around the globe on this field.

The asym. .alpha.-hydroxylation of N,N-diprotected .beta.-amino acid esters I (R1 = Ph, PhCH2, PhCH2OCH2; R2 = H), readily prepd. from the corresponding .alpha.-amino acids, proceeded smoothly at -78 and gave esters I (R2 = HO) in 89-95% yields and with high diastereoselectivity (up to 94% de). In comparison with other asym. .alpha.-hydroxylation procedures this method does not need the use of costly chiral reagents and/or chiral auxiliaries and represents the first example of a procedure affording .beta.-amino-.alpha.-hydroxy acids with full, orthogonal protection.

En 1986, Pierre Jodogne publiait pour l’Istituto storico italiano per l’età moderna e contemporanea le premier tome de son édition des Lettres de Francesco Guicciardini. Vingt ans plus tard, les neuf premiers tomes ont paru et le dixième est actuellement sous presse : la moitié de cette gigantesque entreprise a donc été accomplie, justement l’année où M. Jodogne fête son soixante-dixième anniversaire. La coïncidence de ces dates, que le hasard s’est amusé à combiner, a fourni l’heureux prétex...

Ketones are reported to be conveniently converted into their α-tolylsulfinylated derivatives. This new procedure is based on the reaction of their corresponding trimethylsilyl enol ethers with p-toluenesulfinyl p-tolylsulfone in the presence of tris(dimethylamino)sulfur trimethylsilyldifluoride (TAS-F). Considering that β-ketosulfoxides are key intermediates for the preparation of α,β-unsaturated ketones, this procedure turns out to be of rather broad synthetic relevance.

N-Acetyl-1,3-thiazolidine derivatives of cyclohexanones, when treated with a threefold excess N-bromosuccinimide in anhydrous chloroform at room temperature, smoothly afford N-acetyl-2,3-dihydro-1,4-benzothiazines. This represents the first general route to such heterocyclic system in one step from aliphatic precursors. The synthesis of optically active N-acetyl-2,3-dihydro-1,4-benzothiazines is also reported

Ethanediyl S,S-acetal (1,3-dithiolane) derivatives of 3-oxosteroids, when treated with bromine in anhydrous chloroform at room temperature, undergo ring A aromatization following a dienone-benzene like steroidal skeleton rearrangement that leads to 1,4-dithian fused 4-methylestranes. The easy replacement of the sulphur atoms may afford 4-methylestranes with variously substituted A rings.

γ-Methylene derivatives of α,β-unsaturated ketones are obtained readily by a one-pot procedure exploiting the reaction of O-silylated dienolates with commercially available formaldehyde N, N-dimethyliminium chloride in anhydrous N, N-dimethylformamide, in situ oxidation of the Mannich reaction product with hydrogen peroxide, and elimination of N,N-dimethylhydroxylamine from the resultant N-oxide.

Ketones and carboxylic acid esters are conveniently converted to their α-sulfenylated derivatives. This new procedure is likely to represent the first reliable one for regiospecific monosulfenylation of carbonyl compounds. It is based on the reaction of their trimethylsilyl enol ether derivatives with tetrabutylammonium fluoride in the presence of thiosulfonic S-esters, in anhydrous tetrahydrofuran, under mild conditions, at - 70°C for a few minutes.

A new, very convenient procedure for smooth conversion of primary and secondary alcohols to their corresponding formic acid esters is described. This is based on the use of modified Vilsmeier Haak adducts, obtained from N, N-dimethylformamide and polymersupported triarylphosphine-halogen complexes.

Backgrounds Hereditary transthyretin amyloidosis (ATTRv) presymptomatic subjects undergo multidisciplinary evaluation to detect, as early as possible, a subclinical involvement of multisystem disease. Quantitative sensory testing (QST) that investigates and discriminates the function of C, Aδ and Aβ fibers is included as an instrumental test to monitor nerve fiber function. The purpose of this study was to evaluate the role of QST in the context of the multidisciplinary evaluation in late onset carriers. Methods Four-teen presymptomatic (namely carriers) were enrolled. Subjects underwent thermal [cold and warm detection threshold (CDT, WDT), cold and heat pain (CP and HP)] and tactile QST in four body sites: foot dorsum, distal lateral leg, distal thigh, hand dorsum. Results Overall, presymptomatic subject showed a significant difference in all thermal QST findings compared to the control group. All subjects had at least one altered thermal QST finding; the sites more frequently altered were foot and leg, whilst the thermal modalities which were more frequently abnormal were CDT, WDT and CP. Conclusions Our study highlights the importance of performing thermal QST in subjects carrying TTR mutation, given the high frequency of abnormal findings. Notably, performing both innocuous and painful stimulation in foot and/or leg increases the chance of detecting nerve fiber dysfunction. Moreover, the investigation of the hand may provide useful information in monitoring disease progression before the Predicted Age of Disease Onset (PADO).

The highly stereocontrolled de novo synthesis of L-NBDNJ (the unnatural enantiomer of the iminosugar drug Miglustat) and a preliminary evaluation of its chaperoning potential are herein reported. L-NBDNJ is able to enhance lysosomal α-glucosidase levels in Pompe disease fibroblasts, either when administered singularly or when co-incubated with the recombinant human α-glucosidase. In addition, differently from its D-enantiomer, L-NBDNJ does not act as a glycosidase inhibitor.

The synthesis of (1'S,2'S,4'R) and (1'S,2'R,4'R) stereoisomers of 2'-fluoro-3'-thiacytidine [(2' S)-F-3TC and (2' R)-F-3TC], the earliest examples of oxathiolanyl nucleosides with a fluorine atom in the 'sugar' backbone, is herein reported. From of a variety of synthetic routes devised for their preparation, the Pummerer rearrangement of protected lamivudine sulfoxides was successfully exploited for fluorine atom introduction. Despite the presence of three potentially labile stereocenters in such a small molecule, the (2'R)-isomer of F-3TC exhibited good chemical stability after protective group cleavage. Conversely, the (2'S)-epimer suffered from weak stability, owing to the formation of an undesired cyclization product. Based on the remarkable antiviral efficacy of the parent drugs, the access to 2'-fluorinated oxathiolanyl nucleosides (and more generally, 2'-fluorinated heterocyclic nucleosides) may provide a new source of candidates with antiviral potential.

The combined use of silanes (Et3SiH or PMHS) and I2 as novel N-glycosidation reagents for the synthesis of bioactive oxathiolane nucleosides 3TC and FTC is reported. Both systems (working as anhydrous HI sources) were devised to act as substrate activators and N-glycosidation promoters. Excellent results in terms of chemical efficiency and stereoselectivity of the reactions were obtained; surprisingly, the nature of the protective group at the N4 position of (fluoro)cytosine additionally influenced the stereochemical reaction outcome.

The development of a novel tumor-targeting photosensitizer delivery system, with potential ability to selectively transport the photosensitizer prodrug 5-aminolevulinic acid methyl ester (MAL) into the tumor site has been herein described. Conjugation of MAL to folic acid (FA) via an unnatural β-peptide linker has been carried out almost entirely by an efficient solid phase approach. This molecular system has been devised for possible applications in selective photodynamic diagnosis (PDD) and therapy (PDT).

The synthesis and a preliminary evaluation of the pairing properties of ribo-cyclohexanyl nucleic acids (r-CNA) is herein reported. Incorporation of a single r-CNA nucleotide into natural duplexes did not enhance their stability, while a very high pairing selectivity for RNA was found. As deduced by comparative analysis of Tm and NMR data, a relationship between pairing selectivity and conformational preferences of the "sugar" moiety of r-CNA (and more generally of six-membered nucleic acids) was suggested.

Lipid A is the lipophilic region of lipopolysaccharides and lipooligosaccharides, the major components of the outer leaflet of most part of Gram-negative bacteria. Some lipid As are very promising immunoadjuvants. They are obtained by extraction from bacterial cells or through total chemical synthesis. A novel, semisynthetic approach to lipid As is ongoing in our laboratories, relying upon the chemical modification of a natural lipid A scaffold for the fast obtainment of several other lipid As and derivatives thereof. The first requisite for this strategy is to have this scaffold available in large quantities through a scalable process. Here, we present an optimized fed-batch fermentation procedure for the gram-scale production of lipid A from Escherichia coli K4 and a suitable phenol-free protocol for its purification. A study for regioselective de-O-phosphorylation reaction was then performed to afford pure monophosphoryl lipid A with an attenuated endotoxic activity, as evaluated by cytokine production in human monocytic cell line THP-1 in vitro. The reported method for the large-scale obtainment of monophoshoryl lipid A from the fed-batch fermentation broth of a recombinant strain of E. coli may permit the access to novel semisynthetic lipid A immunoadjuvant candidates.

The overview of de novo approaches to diverse carbohydrates and non-sugar derivatives utilizing 5,6-dihydro-1,4-dithiin-2-yl-methanol as a starting synthon is presented. Various synthetic transformations many of which take place via a single electron transfer mechanism (SET) are compiled. New routes to rare monosaccharides, nitrogen-containing heterocycles and sugar-modified nucleosides are highlighted

A semisynthetic approach to novel lipid A derivatives from Escherichia coli (E. coli) lipid A is reported. This methodology stands as an alternative to common approaches based exclusively on either total synthesis or extraction from bacterial sources. It relies upon the purification of the lipid A fraction from fed-batch fermentation of E. coli, followed by its structural modification through tailored, site-selective chemical reactions. In particular, modification of the lipid pattern and functionalization of the phosphate group as well as of the sole primary hydroxyl group were accomplished, highlighting the unusual reactivity of the molecule. Preliminary investigations of the immunostimulating activity of the new semisynthetic lipid A derivatives show that some of them stand out as promising, new immunoadjuvant candidates.

The study of the base-pairing properties of nucleic acids with sugar moieties in the backbone belonging to the l-series (b-l-DNA, b-l-RNA, and their analogs) are reviewed. The major structural factors underlying the formation of stable heterochiral complexes obtained by incorporation of modified nucleotides into natural duplexes, or by hybridization between homochiral strands of opposite sense of chirality are highlighted. In addition, the perspective use of l-nucleic acids as candidates for various therapeutic applications, or as tools for both synthetic biology and etiology-oriented investigations on the structure and stereochemistry of natural nucleic acids is discussed.

A novel route to 2',3'-dideoxy-β-l-erythro-hexopyranosyl nucleosides equipped with a 1'-(N(6)-benzoyladenin-9-yl) or a 1'-(thymin-1-yl) moiety has been developed. Synthesis of the enantiopure sugar moiety was carried out by a de novo approach based on a domino reaction as the key step. N-Glycosidation was explored via either nucleobase-transfer mechanism (B = T) or in situ anomerization (B = A or T), affording target nucleosides with high overall stereoselectivity.

Last years have witnessed enormous progresses in glycomic field, mainly as a consequence of the crucial role carbohydrates have shown in biological systems. While up to a few years ago attention was mainly focused on the use of easily available D-sugars, a recent interest has emerged around their L-enantiomers, as they have been found to be key components of several bioactive compounds, whether in the form of oligosaccharides, glycopeptides, terpene glycosides or other clinically useful agents. However, L-sugars (L-hexoses especially) are rather rare in nature and not easily accessi- ble from inexpensive sources. As demand for their synthesis in considerable amount and high purity is more and more pressing, intense efforts have been addressed to the development of new and general methodologies for their construction. This review covers the synthetic routes to L-hexoses, mainly those coming from the new century. Methodologies for monosaccharide assembly will comprise de novo approaches, based on carbon chain elongation, hetero Diels-Alder reac- tion, asymmetric dihydroxylation up to the most recent amino acid-catalyzed aldol addition - as well as D-sugar manipula- tion strategies, including epimerization by chemical or enzymatic methods. Application of such protocols for the construc- tion of biologically relevant oligosaccharides and natural products will be also briefly mentioned. In the last two decades a new key role of carbohydrates in living organisms has emerged, as they have shown to be major information carriers between cells and their surround- ings, both in their free form or as glycoconjugates with pro- teins or lipids. This finding has rapidly brought to an increas- ing interest towards several aspects of carbohydrate chemis- try, particularly owing to the potential use of sugars in bio- chemical and pharmaceutical field. The need for specific saccharides in significant amount, in order to thoroughly understand their biological functions, has inspired modern synthetic approaches. The demand for compounds able to mimic natural substances by way of similar structure and/or biological function has stimulated elaboration of innovative preparative procedures in carbohydrate synthesis. The search for analogues of mono- and oligosaccharides resistant to enzymatic degradation has been also carried out. With a re- evaluation of the importance of carbohydrates, analogously to Proteomics and Genomics the term "Glycomics" (1) (or "Glycobiology" (2) or "Glycoscience" (3)) has been coined to refer to the role of carbohydrates in biological events. In view of the various biochemical pathways and disease proc- esses in which carbohydrates are crucially engaged - angio- genesis (4), cancer (5), tissue repair, cardiovascular diseases (6), immune-system function (7), microbial and viral patho- genesis (8), just to name a few of them - the possibilities for their use as therapeutics and diagnostics are numerous and exciting.

During recent years, quantitative proteome profiling has taken advantage of incorporating the traditional stable isotope dilution analysis into global scale or discovery-based proteomic experiments that use mass spectrometers as detectors to allow the pairwise study of differently expressed proteins. Quantitative protein analysis by means of the isotope-coded affinity tag (ICAT) method and tandem mass spectrometry (MS) enables the pairwise comparison of protein expression levels in biological samples. Herein, a modified ICAT reagent, named BAA-ICAT (beta-alanine-arm-ICAT) in which the polyether linker is replaced by a more water-soluble polyamide one, was investigated.

An asymmetric synthesis of anti-2,3-diamino acids is reported. The enolates of N,N-dibenzylated b3-amino esters were treated with di-tert-butyl azodicarboxylate (DBAD) to afford their N0,N00-di-Boc-2-hydrazino derivatives with excellent anti diastereoisomeric ratio. Final Boc removal and reductive cleavage of the hydrazino bond led to the expected 2,3-diamino esters having only one free amino group. In comparison with other asymmetric C-2 amination procedures, this method does not need the use of expensive chiral reagents and/or chiral auxiliaries, while leads to products which can be orthogonally protected.