Jean-Claude Depezay

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 thiosugars as weak inhibitors of glycosidases

Abstract A series of enantiomerically pure thiosugars (1,6-dideoxy-1,6-thio-D-mannitol or L-iditol, 1,5-dideoxy-1,5-thio-L-gulitol or D-glucitol and 2,5-dideoxy-2,5-thio-L-iditol or D-mannitol, and their corresponding sulfoxide or sulfone) was synthesized via thiocyclization of C2-symmetric bis-epoxides, and subsequently followed by ring isomerization in few cases. These compounds have been evaluated as inhibitors of several glycosidases (α- and β-D-glucosidases, α-D-mannosidase and α-L-fucosidase).

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.

Polyhydroxylated nortropanes starting from D-glucose : synthesis of homochiral (+) and (-)-calystegines B2

Abstract The cycloheptano-isoxazoline 1 , prepared from D-glucose, is converted to 6,7-dideoxy cycloheptitols which are suitable precursors for the synthesis of enantiomerically pure (+) and (−)-Calystegines B 2 .

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.

Access to polyhydroxylated cycloheptane derivatives through stereoselective nitrile oxide intramolecular cycloaddition. Synthesis of an analogue of calystegine B2

Abstract A hydroxymethyl substituted calystegine B 2 has been synthesized stereoselectively by intramolecular cycloaddition of an olefinic nitrile oxide derived from D-glucose.

Synthesis of (-)-Muricatacin and (-)-(5R,6S)-6-acetoxy-5-hexadecanolide, the Mosquito oviposition attractant pheromone, from D-isoascorbic acid

Abstract From D -isoascorbic acid, a general approach to enantiomerically pure hydroxy γ-butyro and δ-valero lactones, (-)-Muricatacin and (-)-(5 R ,6 S )-6-acetoxy-5-hexadecanolide, via a four carbon atoms bis-epoxide equivalent, is reported.

Synthesis and evaluation as glycosidase inhibitors of 2,5-imino-d-glucitol and 1,5-imino-d-mannitol related derivatives

Selectively functionalized 2,5-imino-D-glucitol and 1,5-imino-D-mannitol derivatives were synthesized and tested as precursors of hydrolytically resistant pseudo-disaccharides. Among them N-acetyl-6-amino-6-deoxy-2,5-imino-D-glucitol (11) and N-acetyl-6-amino-6-deoxy-1,5-imino-D-mannitol (12) were found potent and specific inhibitors against beta-D-glucosidase and alpha-L-fucosidase, respectively.

Thiosugars from D-mannitol

Abstract Enantiomerically pure thiosugars, with a thiepan, tetrahydrothiopyran or tetrahydrothiophene backbone, have been synthesized by thio-heterocyclization of enantiopure C 2 -symmetric bis-epoxides and possibly ring contraction.