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Aziridine carboxylate from D-glucose: synthesis of polyhydroxylated piperidine, pyrrolidine alkaloids and study of their glycosidase inhibition.

The D-glucose derived aziridine carboxylate 5 was obtained from (E)-ethyl-6-bromo-1,2-O-isopropylidene-3-O-benzyl-5-deoxy-alpha-D-xylo-5-eno-heptofuranuronate 4 through conjugate addition of benzylamine and in situ intramolecular nucleophilic expulsion of bromine. The regioselective aziridine ring-opening, using water as a nucleophile, resulted in the alpha-hydroxy-beta-aminoester 6, which was exploited in the synthesis of six and five membered azasugars 1b/1c and 2b/2c, respectively. The glycosidase inhibitory activity of the title compounds was evaluated.

Alkaloids↗

The dimerization of delta-1-piperidine-2-carboxylic acid.

The l-amino acid oxidase of Mytilus edulis has been used to oxidize l-lysine on a large scale in the presence of catalase. The alpha-oxo acid derived from lysine cyclizes to a Schiff base, which readily dimerizes. The dimer undergoes spontaneous dehydration and decarboxylation to form 1,2,3,4,5,6,7,8-octahydropyrido[3,2-a]-indolizin-10(4bH)-one. This structure was established by a study of its molecular weight and infrared, nuclear-magnetic-resonance and mass spectra.

Amino Acid Oxidoreductases↗

ADL 8-2698, a trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidine, prevents gastrointestinal effects of intravenous morphine without affecting analgesia.

ADL-8-2698 is a novel peripherally restricted opioid antagonist that may selectively prevent opioid-induced gastrointestinal effects without reversing analgesia. Gastrointestinal transit time (lactulose hydrogen breath test) was measured in 14 volunteers with oral and intravenous placebo, oral placebo and intravenous morphine (0.05 mg x kg(-1)), and oral ADL 8-2698 (4 mg) and intravenous morphine (0.05 mg x kg(-1)) in a double blind, cross-over study. Morphine prolonged gastrointestinal transit time from 69 to 103 minutes (P = .005); this was prevented by ADL 8-2698 (P = .004). Postoperatively, 45 patients were randomly assigned in a double-blind fashion to receive ADL 8-2698 (4 mg) or placebo and intravenous morphine (0.15 mg/kg) or to receive oral and intravenous placebo. Analgesia and pupil constriction were measured. Morphine analgesia and pupil constriction were unaffected by ADL 8-2698 and differed from placebo (P < .002). We conclude that ADL 8-2698 prevents morphine-induced increases in gastrointestinal transit time by means of selective peripheral opioid anitagonism without affecting central opioid analgesia.

Adult↗

Antimicrobial activity studies on some piperidine and pyrrolidine substituted halogenobenzene derivatives.

The in vitro antibacterial and antifungal activities of the compounds synthesised from some 1,2,3,5-tetrahalogeno benzenes in presence of sodium piperidide and sodium pyrrolidide (2,6-dipiperidino-1,4-dihalogenobenzenes; 2,6-dipyrrolidino-1,4-dibromobenzene; 2,4,6-tripyrrolidino chlorobenzene; and 1,3-dipyrrolidino benzene) were investigated. The in vitro antimicrobial activities were screened against the standard strains: Staphylococcus aureus ATCC 25923 and Bacillus subtilis ATCC 6633 as Gram positive, Yersinia enterocolitica ATCC 1501, Escherichia coli ATCC 11230 and Klebsiella pneumoniae as Gram negative, and Candida albicans as yeast-like fungus. Compounds (3, 5, 6, 7) inhibited the growth of all the test strains at MIC values of 32-512 microg/ml. None of the four compounds (1, 2,4,8) studied showed antimicrobial activity against any of the test strains within the MIC range 0.25-512 micro/ml.

Anti-Infective Agents↗