6C-butylglucoses from glucuronolactone: Suppression of silyl migration during borohydride reduction of lactols by cerium (III) chloride: Inhibition of phosphoglucomutase

The synthesis of the epimeric 6C-butylglucoses from D-glucuronolactone is reported. The sodium borohydride reduction of two fully protected lactols is highly stereoselective but is accompanied by migration of a silyl protecting group; in the presence of cerium(III) chloride, there is little change in the stereoselectivity but the migration of the silyl group is suppressed. 6R-6C-Methylglucose and 6R-6C-butlylglucose are both better inhibitors of phosphoglucomutase than their 6S epimers

6R-, and 6S, -6C-methylglucose from D-glucuronolactone: Efficient synthesis of a seven carbon fucose analogue: Inhibition of some enzymes of primary metabolism

Syntheses of the two epimeric 6C-methylglucoses from D-glucuronolactone rely on a non-stereoselective reduction of an intermediate lactol. A highly stereoselective reduction of a silylated lactol, which is accompanied by a silyl migration, gives easy access to 6S-6C-methylglucose - a seven carbon fucose analogue - in five steps from glucuronolactone in an overall yield of 40%. An azido analogue of 6R-6C-methylglucose is also reported, Such compounds may provide new materials for the selective inhibition of various enzymes of primary metabolism including glucokinase, glucose-6-phosphatase, and phosphoglucomutase. X-ray crystal structures of (1S,3R,4S,5S,7R,8R)-3-methyl-7,8-O-isopropylidene-3,4,7,8-tetr ahydroxy-2,6 -dioxabicyclo[3,3,0]-octane and 7-deoxy-1,2-5,6-di-O-isopropylidene-L-glycero-α-D-gluco-hepto furanose are reported

Conformationally constrained butyrophenones with affinity for dopamine (D(1), D(2), D(4)) and serotonin (5-HT(2A), 5-HT(2B), 5-HT(2C)) receptors: synthesis of aminomethylbenzo[b]furanones and their evaluation as antipsychotics

A series of novel conformationally restricted butyrophenones (6-aminomethyl-4,5,6,7-tetrahydrobenzo[b]furan-4-ones bearing 4-(6-fluorobenzisoxazolyl)piperidine, 4-(p-fluorobenzoyl)piperidine, 4-(o-methoxyphenyl)piperazine, 4-(2-pyridyl)piperazine, 4-(2-pyrimidinyl)piperazine, or linear butyro(or valero)phenone fragments) were prepared and evaluated as antipsychotic agents by in vitro assays for affinity for dopamine receptors (D(1), D(2), D(4)) and serotonin receptors (5-HT(2A), 5-HT(2B), 5-HT(2C)), by neurochemical studies, and by in vivo assays for antipsychotic potential and the risk of inducing extrapyramidal side effects. Potency and selectivity depended mainly on the amine fragment connected to the cyclohexanone structure. Compounds 20b, with a benzoylpiperidine moiety, and 20c, with a benzisoxazolyl fragment, were selective for 5-HT(2A) receptors. The in vitro and in vivo pharmacological profiles of N-[(4-oxo-4,5,6, 7-tetrahydrobenzo[b]furan-6-yl)methyl]-4-(p-fluorobenzoyl)piperidine (20b, QF1003B) and N-[(4-oxo-4,5,6, 7-tetrahydrobenzo[b]furan-6-yl)methyl]-4-(6-fluorobenzisoxazol-3-yl)p iperidine (20c, QF1004B) suggest that they may be effective as antipsychotic (neuroleptic) drugs