Gino Ronco

Nucleoside Analogues with a Novel Glycone Based on the Benzo[C]Furan Core

Abstract Routes to novel nucleoside analogues based on 1, 3-dihydrobenzo[c]furan have been investigated. Thus l-(1, 3-dihydro-3-hydroxymethylbenzo[c]furan-1-yl)-thymine, an analogue of d4T, was obtained as two diastereoisomers. The cis compound (quasi β-D/α-L stereochemistry) was obtained pure but the trans compound was only 90% pure. A purine analogue with a four atom spacer group between base and glycone was also prepared. The conformation of these constrained nucleosides was studied by molecular modelling.

Substitution effects on the liquid crystalline properties of D,L-xylitol amphiphiles

In this article we describe the self-assembling properties of alkyl substituted xylitols in relation to both thermotropic and lyotropic liquid crystalline mesophases. Three series of substituted xylitols were prepared where aliphatic chains of varying length were attached to a xylitol moiety via ether, thioether and ester linking groups. The thermotropic properties were investigated by thermal polarized light microscopy and differential scanning calorimetry, and evaluated as a function of chain length and linking group. The lyotropic phase behaviour was investigated via the addition of water to each material at room temperature. The efficiency for forming thermotropic phases was found to be reversed for the lyotropic phases in respect of the three series, i.e. as a function of the linking unit.

The dependence of mesomorphic behaviour on the extent of hydrogen-bonding in sugar derived polyols

The thermotropic liquid crystalline properties of a variety of chiral and racemic dodecyloxy substituted polyols derived from carbohydrates were investigated as a function of the number of hydroxyl groups associated with the polyol unit. It was found that all of the materials exhibited smectic A* phases, and that the clearing points increased monotonically with the number of hydroxyl groups. The linear increase was found to be independent of stereochemical structure and the degree of optical purity. A model suggesting that the smectic A* phase has an internal microphase separated structure can be used to account for these observations.

Synthesis of novel bis (glycosyl) ethers as bolaamphiphile surfactants

Abstract We have synthesized new bolaamphiphile carbohydrate derivatives having general structures AO(CH 2 ) n OB or [AO(CH 2 ) n ] 2 C(OH)R. The hydrophilic heads A and B (identical or different) are d -glucose, d -galactose, xylitol, or their respective protected derivatives, and R is an alkyl chain. The carbohydrate units A and B are condensed in the first step as di- O -isopropylidene derivatives with either α,ω-dibromo- or dimesyl-alkanes in the presence of powdered KOH in 9:1 or 4:1 toluene-Me 2 SO. Appropriate choice of either selective or total deprotection of acetal groups and either regioselective esterification or regiospecific etherification allows modulation of either the hydrophilic or the lipophilic character of these new surfactants. The ether junctions between the alkyl chain and carbohydrate moiety proved resistant to severe acid-hydrolytic conditions.

Synthesis of Ether-Linked Di- and Trisaccharide Derivatives Part I- Synthesis Of Disaccharides from 5,6-Anhydro-D-Glucose Derivatives

Abstract We have synthesized a series of A-O-B disaccharides of the type A(6→n)B obtained by linking the D-glucose derivative (A) with each of the D-fructose, D-galactose, D-glucose, xylitol and glycerol derivatives (B). The key step in each case is the nucleophilic attack of a monosaccharide alkoxide on the C-6 site of 3-O-alkyl-5,6-anhydro-1,2-O-isopropylidene-α-D-glucofuranose; each reaction was performed in toluene-DMSO and using KOH as the base.

Facile separation of chiral 1,3-dihydrobenzo[c]furan derivatives using a d-xylose moiety as a protecting group

Abstract 1,2-O-Isopropylidene-α- d -xylofuranose has been used to protect one aldehyde group of o-phthalaldehyde. This chiral protecting group acts as a resolving agent and this leads to separable diastereoisomers when a new stereogenic centre is created by the conversion of the second aldehyde group to a benzyloxyhydroxyethyl chain. These separated diastereoisomers were cyclised to 1,3-dihydrobenzo[c]furans with retention of chiral integrity at the C3 site thus allowing further elaboration to enantiomerically pure nucleoside analogues.

Synthesis of Monoesters as Surfactants and Drugs from D-Glucose

Abstract We have synthesized a series of monoesters from D-glucose corresponding to the structures 3-O-acyl, 6-O-acyl-1,2-O-isopropylidene-α-D-glucofuranose and 3-O-acyl-D-glucose, following the sequence of reactions : D-glucose → diacetone glucose → acylation → partial or total deprotection. These compounds were prepared as either potential non-ionic surfactants (fatty acid esters and perfluoroalkylated ester) or antitumour drugs (n-butyric esters). Results concerning surface activity, toxicity and antitumour effects are reported. A novel method for obtaining partially deprotected 6-O-acyl esters from their corresponding 3-O-acyl isomers is reported. Deprotection conditions have been studied and a higher selectivity in partial deprotection has been achieved. We have given particular attention to the choice of solvents and reagents in order not to limit the extent to which the products might be applied.

Stereoselective synthesis of α-aminonitriles at non-anomeric positions of monosaccharides

Abstract α-Aminonitriles have been stereoselectively introduced at non-anomeric positions of monosaccharides, in which the carbon C-α is one of the atoms of the sugar ring. Target compounds were prepared from various ulose derivatives and amines using titanium(IV) isopropoxide as a mild and effective Lewis acid.

An homologous series of 6-O-n-alkyl-alpha-D-galactopyranoses: synthesis and thermotropic mesomorphic properties

An homologous series of 6- O - n -alkyl- alpha -D-galactopyranoses has been prepared. The length of the terminal chains has been varied systematically and the effect on the liquid crystal transition temperatures studied. Most homologues of the series exhibit enantiotropic smectic A* phases. X-ray analysis indicates a lamellar structure for the smectic A* phase with hydrogen-bonded carbohydrate cores at the layer centre, either with no interdigitation of the tilted terminal alkyl chains but with a high degree of chain melting, or with some degree of chain intercalation. The 6- O - n -alkyl- alpha -D-galactopyranoses possess clearing points at higher temperatures than those of the corresponding n -alkyl alpha -D-galactopyranosides. The introduction of a higher degree of hydrogen bonding by the replacement of the oxygen atom in the ether linkage between the chain and the carbohydrate ring by an amide linkage leads to higher transition temperatures. The dependence of the liquid crystalline behaviour on the po...

Diastereomeric resolution of nucleoside analogues, new potential antiviral agents, using high-performance liquid chromatography on polysaccharide-type chiral stationary phases.

This paper describes the separation of the four sets of stereoisomers of nucleoside analogs, new potential antiviral agents by direct analytical HPLC methods using derivatized cellulose and amylose chiral stationary phases. The resolution was made using normal-phase methodology with a mobile phase consisting of n-hexane-alcohol (ethanol or 2-propanol) in various percentages, and a silica-based cellulose tris-3,5-dimethylphenylcarbamate (Chiralcel OD-H), or tris-methylbenzoate (Chiralcel OJ) and a silica-based amylose tris-3,5-dimethylphenylcarbamate (Chiralpak AD) or tris-(S)-1-phenylethylcarbamate (Chiralpak AS). The effects of structural features on the extent of discrimination between the stereoisomers were examined through the retention, the selectivity and the resolution factors as well as the elution order. Baseline separation (Rs>1.5) was easily obtained in many cases. The resolution results were complementary between the different columns.