Albert Nguyen Van Nhien

Tetrabutylammonium prolinate-based ionic liquids: a combined asymmetric catalysis, antimicrobial toxicity and biodegradation assessment

Chiral ionic liquids (CILs) tetrabutylammonium-(S)-prolinate, tetrabutylammonium-(R)-prolinate and tetrabutylammonium trans-4-hydroxy-(S)-prolinate were investigated as chiral additives in the Pd-catalyzed enantioselective hydrogenation of α,β-unsaturated ketones. These CILs were easily prepared in one step from the aminoacid and tetrabutylammonium hydroxide and characterized (NMR, IR, optical rotation, elemental analysis, DSC, viscosity, decomposition temperature). The research strategy was to assess the antimicrobial toxicity (>20 strains) and biodegradability (OECD 301D) of the CILs at the same time as undertaking the asymmetric catalysis study. The Pd-catalyzed enantioselective hydrogenation of the carbon–carbon double bond of α,β-unsaturated ketones under mild conditions (room temperature, 1 atm of H2) in different solvents with CILs present. The best results were obtained in i-PrOH after 18 hours of reaction with a i-PrOH/IL ratio of 5. While all three CILs have low antimicrobial toxicity to a wide range of bacteria and fungi, tetrabutylammonium-(S)-prolinate, tetrabutylammonium-(R)-prolinate and tetrabutylammonium trans-4-hydroxy-(S)-prolinate did not pass the Closed Bottle biodegradation test.

Interface Stability of a TiO2/3‐Methoxypropionitrile‐Based Electrolyte: First Evidence for Solid Electrolyte Interphase Formation and Implications

We report an in-depth study focusing on the stability of a benchmark electrolyte composition based on a low-volatile 3-methoxypropionitrile (MPN) solvent employed in dye-sensitized solar cells. In the presence of TiO2, the semi-conductor surface plays a catalytic role in the thermal degradation of the electrolyte, which induces, among other effects, the nucleation and growth of a uniform solid electrolyte interphase (SEI) layer that wraps TiO2. On the basis of our actual understanding, we argue that SEI formation is responsible for triiodide depletion in the electrolyte during ageing and also has a simultaneous impact on TiO2 optoelectronic properties through the onset of a visible-light absorption tail, energy modification of intraband trap states, and the induction of an increase in both electron lifetime and transport time in TiO2. In-depth characterization of this layer by using XPS and ToF-SIMS indicates that the chemical composition of this SEI results from solvent and additive degradation, that is, iodide, sulfur, cyano, nitrogen, carbon, and imidazolium rings. The SEI thickness, its content, and the concentration profile strongly vary depending on the ageing conditions. The outcome of this new finding is discussed in comparison with literature observations and stresses the difficulties in reaching long-term stability at 85 °C by using MPN-based electrolytes unless new interfacial engineering is accomplished to impede pinholes between dye molecules on TiO2.

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.

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.

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.

The synthesis of polyoxygenated, enantiomerically pure cyclopentane derivatives on route to neplanocin A stereoisomers via alkylidenecarbene species prepared from sugar templates

Our new method for the generation of alkylidenecarbenes, based on the reaction of trimethylsilylazide/Bu(2)SnO with alpha-cyanomesylates, has been applied to the synthesis of enantiomerically pure polyhydroxylated cyclopentane derivatives from conveniently functionalized sugar intermediates prepared from D-mannose. The stereoselectivity of the 1,5 C-H insertion reaction leading to the major trans-isomers (8a,b) has been assigned by (1)H RMN spectroscopic data, and correctly rationalized by a computational analysis at DFT level. Compounds 8a and 8b have been designed as suitable intermediates for the synthesis of neplanocin A enantiomer.

1,6‐C‐H and 1,5‐O‐Si Insertion Reactions of Alkylidenecarbene Derivatives of Monosaccharides*

A new protocol has been developed for the generation of alkylidenecarbene derivatives of monosaccharides based on the reaction of trimethylsilylazide and Bu2SnO with α‐cyanomesylates derived from uloses. When this method is applied to conveniently functionalized carbohydrate derivatives it provides novel heterocyclic ring systems by the rare 1,6‐C‐H or 1,5‐O‐Si insertion reactions. * This work is dedicated to the memory of Professor Jacques H. van Boom.

Synthesis and in vitro activity of novel N-3 acylated TSAO-T compounds against HIV-1 and HCV

Preparation of a small library of derivatives of the potent HIV-1 Reverse Transcriptase inhibitor TSAO-T bearing mono or di-carbonyl substituents (designed after docking analysis) at position N-3 is reported. A one-pot synthetic methodology has been developed that involves: (i) mono-reaction of TSAO-T with glutaryl dichloride under phase transfer conditions and (ii) in situ acyclic substitution of the remaining chloro atom by oxygen or nitrogen nucleophiles. The method is compatible with the polyfunctionality of the TSAO-T molecule, proceeds with high conversion yields and allows introducing molecular diversity. The anti-HIV-1 and -HCV activity was studied in cell culture. The new N-3 acylated TSAO-T derivatives are active against HIV-1 (nanomolar range). Anti-HCV activity was observed in the micromolar range, that is at compound concentrations that were found cytostatic against human T-lymphocytes.

Click Reactions as a Key Step for an Efficient and Selective Synthesis of D-Xylose-Based ILs

d-Xylose-based ionic liquids have been prepared from d-xylose following a five steps reaction sequence, the key step being a click cycloaddition. These ionic liquids (ILs) have been characterized through classical analytical methods (IR, NMR, mass spectroscopy, elemental analysis) and their stability constants, Tg and Tdec, were also determined. Considering their properties and their hydrophilicity, these compounds could be alternative solvents for chemical applications under mild conditions.