Didier Le Nouën

Ring closing metathesis as an efficient approach to branched cyclitols and aminocyclitols: a short synthesis of valiolamine

Abstract Ring closing metathesis of sugar-derived 1,6 dienes is the key step for the construction of highly functionnalized cyclohexenes, precursors of branched cyclitols and aminocyclitols. The method has been used for a short synthesis of valiolamine.

Chiral 5-Methyl-trihydroxypyrrolidines—Preparation from 1,2-Oxazines and Glycosidase Inhibitory Properties

Abstract Chemical transformations of chiral 1,2-oxazines 4, 5 gave the 2,5,6-trideoxy-2,5-imino d -alditols 12b, 13b in the d -altritol and d -talitol series, respectively. Basic aldehyde epimerisation led to the d -allitol isomer 15b. Compound 12b is a potent α- l -fucosidase and α- d -galactosidase inhibitor.

Synthesis of 4-amino-4,5-dideoxy-l-lyxofuranose derivatives and their evaluation as fucosidase inhibitors

The nitrone 4 (4,5-dideoxy-4-hydroxylamino-3,4-O-isopropylidene-L-lyxofuranose) was synthesised from D-ribose and used as key intermediate for the preparation of fucosidase inhibitors. We describe two transformations of 4. Hydrolysis with aqueous sulfur dioxide gave the known potent nanomolar inhibitor 4-amino-4,5-dideoxy-L-lyxofuranose (3). 1,3-Dipolar cycloaddition with enol ethers led to the related 1,2,5,6-tetradeoxy-2,5-imino-L-altroheptonic ester 2a, acid 2b and the corresponding heptitol 2c. The new iminosugars have been evaluated for their inhibitory activity against α-L-fucosidase from bovine kidney. The alcohol 2c turned out to be a potent inhibitor in the same range as the amino-sugar 3 (K(i)=8 vs 10nM).

New stereocontrolled transformations in the imidazolosugar series

The isomeric imidazolopyrrolidinose 1, imidazolopiperidinose 2 and imidazoloazepanose 3, potential glycosidase inhibitors, were obtained in several steps from d-glucose.

Long-Term Biostability of Pet Vascular Prostheses

PET Vascular prostheses are susceptible to physical modification and chemical degradation leading sometimes to global deterioration and rupture of the product. To understand the mechanisms of degradation, we studied 6 vascular prostheses that were explanted due to medical complications. We characterized their level of degradation by comparing them with a virgin prosthesis and carried out physicochemical and mechanical analyses. Results showed an important reduction of the fabric’s mechanical properties in specific areas. Moreover, PET taken from these areas exhibited structural anomalies and was highly degraded even in virgin prostheses. These results suggest that vascular prostheses have weak areas prior to implantation and that these areas are much more prone to in vivo degradation by human metabolism. Manufacturing process could be responsible for these weaknesses as well as designing of the compound. Therefore, we suggest that a more controlled manufacturing process could lead to a vascular prosthesis with enhanced lifespan.

EXPEDITIOUS SYNTHESES OF IMIDAZOLE C-NUCLEOSIDES (=C-GLYCOSYLIMIDAZOLES) FROM CARBOHYDRATES AND FORMAMIDINE ACETATE

Pyrolysis of the neat hydrochloride salts of imidazolyl-tetritols 6, 8, and 9 led to the 4-glycofuranosyl-1H-imidazole anomer mixtures 2/3, 4/5, and ent-4/ent-5, respectively. The same pairs of C-nucleosides were also obtained in one-pot procedures by microwave irradiation of mixtures containing formamidine acetate (=formimidamide acetic acid salt), a few drops of H2O, and the appropriate hexose or hexulose, i.e., D-fructose (or D-glucose), D-galactose, and L-sorbose, respectively. Microwave irradiation clearly brought about sequential double condensation of formamidine with hexoses or hexuloses and acid-catalyzed intramolecular cyclization of the intermediate linear imidazolyl-tetritols.