Denis Postel

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.

Novel spirohydantoins of d-allose and d-ribose derived from glyco-α-aminonitriles

Abstract The synthesis of 3-spirohydantoin derivatives of d -allose and d -ribose is reported. The key step is the stereoselective conversion of glyco-α-aminonitriles from ulose derivatives of d -glucose and d -xylose using titanium(IV) isopropoxide as a mild and efficient catalyst. Cyclisation of the glyco-α-aminonitriles give the target spirohydantoins.

Physico-chemical properties and cytotoxic effects of sugar-based surfactants: Impact of structural variations

Surfactants derived from the biorefinery process can present interesting surface-active properties, low cytotoxicity, high biocompatibility and biodegradability. They are therefore considered as potential sustainable substitutes to currently used petroleum-based surfactants. To better understand and anticipate their performances, structure-property relationships need to be carefully investigated. For this reason, we applied a multidisciplinary approach to systematically explore the effect of subtle structural variations on both physico-chemical properties and biological effects. Four sugar-based surfactants, each with an eight carbon alkyl chain bound to a glucose or maltose head group by an amide linkage, were synthesized and evaluated together along with two commercially available standard surfactants. Physico-chemical properties including solubility, Krafft point, surface-tension lowering and critical micellar concentration (CMC) in water and biological medium were explored. Cytotoxicity evaluation by measuring proliferation index and metabolic activity against dermal fibroblasts showed that all surfactants studied may induce cell death at low concentrations (below their CMC). Results revealed significant differences in both physico-chemical properties and cytotoxic effects depending on molecule structural features, such as the position of the linkage on the sugar head-group, or the orientation of the amide linkage. Furthermore, the cytotoxic response increased with the reduction of surfactant CMC. This study underscores the relevance of a methodical and multidisciplinary approach that enables the consideration of surfactant solution properties when applied to biological materials. Overall, our results will contribute to a better understanding of the concomitant impact of surfactant structure at physico-chemical and biological levels.

Reactivity of D-fructose and D-xylose in acidic media in homogeneous phases

Chemistry development of renewable resources is a real challenge. Carbohydrates from biomass are complex and their use as substitutes for fossil materials remains difficult (European involvement on the incorporation of 20% raw material of plant origin in 2020). Most of the time, the transformation of these polyhydroxylated structures are carried out in acidic conditions. Recent reviews on this subject describe homogeneous catalytic transformations of pentoses, specifically toward furfural, and also the transformation of biomass-derived sugars in heterogeneous conditions. To complete these informations, the objective of this review is to give an overview of the structural variety described during the treatment of two monosaccharides (D-Fructose and D-xylose) in acidic conditions in homogeneous phases. The reaction mechanisms being not always determined with certainty, we will also provide a brief state of the art regarding this.

A novel approach to unsaturated acyclic nucleoside analogues and the first synthesis of d4T by ring closure metathesis

Novel unsaturated acyclic nucleoside analogues, 1-{1-[1-(hydroxymethyl)prop-2-enyloxy]prop-2-enyl}uracil, 1-{1-[1-(hydroxymethyl)prop-2-enyloxy]prop-2-enyl}thymine and 1-{1-[1-(hydroxymethyl)prop-2-enyloxy]prop-2-enyl}cytosine have been prepared in good yield from uridine and 5-methyluridine by periodate cleavage followed by a double Wittig reaction which introduces two vinyl groups. The thymine derivative underwent ring closure metathesis to give a novel synthesis of d4T.

Synthesis of acyclic bis-vinyl pyrimidines: a general route to d4T via metathesis

Unsaturated acyclic pyrimidine analogues, 1-{1-[1-(hydroxymethyl)prop-2-enyloxy]prop-2-enyl}uracil, 1-{1-[1-(hydroxymethyl)prop-2-enyloxy]prop-2-enyl}thymine and 1-{1-[1-(hydroxymethyl)prop-2-enyloxy]prop-2-enyl}cytosine having two asymmetric carbon atoms have been prepared in good yield starting from uridine and 5-methyluridine. The bis-vinyl thymine derivative underwent ring closure metathesis to give d4T, thus providing a novel synthesis of this compound.

Novel conformationally restricted glycoamino acids from glyco-α-aminonitriles as potent turn mimics in peptide synthesis

Abstract Our previously described glycoaminocyanation procedure using Ti(O i Pr) 4 and TMSiCN has been applied to introduce amino acid and peptide moieties on a monosaccharide. Selective reduction using NaNH 4 –CoCl 2 and Pd(C), respectively, is described. Restricted conformation of the new glycoamino acids favours intramolecular cyclisation to give the corresponding oxopiperazine 5a – b and 12a – b . The target acyclic compound I was obtained when the peptide derivative was displaced from the complex using KCN. Hydrolysis of the glycospirohydantoin 18 to give the glycoamino acid II is also described.

Enantiomeric d4T analogues and their structural determination

Asymmetric synthesis of d4T analogues having a benzo[c]furan moiety with two asymmetric carbon atoms was realized using Sharpless asymmetric dihydroxylation as the key step in a synthesis starting from o-phthalaldehyde. Enantiomeric purities were determined by analytical chiral HPLC with an amylose-derived stationary phase, while the absolute configurations were established by X-ray crystallography.

New 4-amino-5-H-2,3-dihydroisothiazole-1,1-dioxides from sugar α-aminonitriles using the CSIC reaction

Abstract 4-Amino-5- H -2,3-dihydroisothiazole-1,1-dioxide ring was attached to a monosaccharide ring system by carbanion-mediated sulfonate intramolecular cyclisation (CSIC) of either secondary or tertiary aminonitrilesulfonamide carbohydrate derivatives using NaH, Cs 2 CO 3 or BuLi as a base. These new bicyclic systems were used as glycone precursors of aza analogues of TSAO RT inhibitors. We report the first synthesis of an aza analogue of TSAO-m 3 T.