Lydie Poitout

Synthesis of azasugars as potent inhibitors of glycosidases

A series of enantiomerically pure azasugars (2,5-dideoxy-2, 5-imino-D-mannitol, 1-deoxynojirimycin, 1-deoxymannojirimycin, and related compounds) was synthesized from D-mannitol via aminoheterocyclization of C2-symmetric bis-epoxides and subsequently followed by ring isomerization in few cases. These compounds have been evaluated as inhibitors of several glycosidases (alpha- and beta-D-glucosidases, alpha-D-mannosidase and alpha-L-fucosidase). Inhibition studies indicate notably that the polyhydroxylated azepanes are inhibitors of glycosidases, with Ki in the micromolar range.

Polyhydroxylated piperidines and azepanes from D-mannitol synthesis of 1-deoxynojirimycin and analogues

Abstract D -mannitol and L -iditol bis-epoxides, easily obtained from D -mannitol, are convenient substrates for the synthesis of polyhydroxylated piperidines and azepanes, via a nucleophilic opening of one epoxy function followed by a spontaneous intramolecular ring closure. Using this strategy 1-deoxynojirimycin and analogues were prepared.

Synthesis of sugar-like amino-carboxylic acids from D-mannitol

Abstract 6-Amino-2,5-anhydro-6-deoxy- D -gluconic and L -gulonic acid derivatives, conformationally restricted sugar-like amino-carboxylic acids which mimic dipeptides, have been synthesized by a silica gel assisted azidolysis of enantiomerically pure bis-epoxides.

Design, synthesis and binding affinities of novel non-peptide mimics of somatostatin/sandostatin®

Abstract Based on molecular modelling studies of Sandostatin®, sugar-based derivatives I-VI were prepared as potential non-peptide mimics of somatostatin/Sandostatin®. These compounds displaced 3-[ 125 I]-Tyr 11 -SRIF-14 from the somatostatin receptor on membranes of rat cerebral cortex with IC 50 values between 10 and 15 μM.

Synthesis of azasugars. Part 2 isomerization of polyhydroxylated azepanes

Abstract Isomerization of enantiopure C2-symmetric 3,5-dihydroxyazepane derivatives has been studied. The neighboring nitrogen participation occurs during mesylation to give a chloromethylpiperidine, whereas from the l -ido- azepane a chiral bridged morpholine structure (1R-(6endo, 7exo)-8-oxa-3-azabicyclo[3.2.1]octane-6,7-diol) is obtained under Mitsunobu conditions.

Synthesis of substituted imidazopyrazines as ligands for the human somatostatin receptor subtype 5

A new preparation of trisubstituted imidazopyrazines and dihydroimidazopyrazines via parallel synthesis using aminoacids and bromoketones resulted in the discovery of non-peptidic sst5 selective agonists.

Synthesis of azasugars. Part 1 isomerization of polyhydroxylated piperidines

Abstract N- Benzyl -3,4- di -O- benzyl-1,5-dideoxy-1,5-imino- d -glucitol and l -gulitol undergo easy isomerization, mainly either by ring contraction, or either by SN 2 inversion at C2. This isomerization performed by bis-hydroxyl activation allows to access to 2,5-dideoxy-2,5-imino- l -iditol, 5-epi-DNJ, DMDP, and DMJ.

Novel non-peptide ligands for the somatostatin sst3 receptor.

A series of imidazole derivatives has been prepared using high throughput parallel synthesis. Several compounds showed high affinity (Ki in 10(-6)-10(-8) M range) and selectivity at recombinant human somatostatin receptor subtype 3 (hsst3).

Synthesis of Peptidomimics Through Sugar-Based Scaffolds

Poor oral bioavailability, low metabolic stability towards proteolysis and rapid excretion via both liver and kidneys displayed by innumerable peptides of potential therapeutic value has generated an intensive search for peptidomimics (1-2). A possible approach of such nonpeptidal peptidomimics is to replace the peptide by a scaffold that distributes in the space the peptidal side chains of amino acids essential for biological activity and mimics the bioactive conformation of the peptide.