Bodo Junge

Untersuchungen zur struktur des α-d-glucosidaseinhibitors acarbose

Abstract Hydrolysis of the pseudotetrasaccharide acarbose ( 1 ), a potent inhibitor of intestinal α- d -glucosidases and an effective oral antidiabetic agent, gave d -glucose and a tricyclic compound (1 R ,2 S ,3 R ,4a S ,7 R ,8 S ,8a S ,9a R )-1,2,3,4a,7,8,8a,9a-octahydro-1,2,7,8-tetrahydroxy-3- [(1 R )-1-hydroxyethyl]-6-hydroxymethylpyrrolo-[2,1- b ]benzoxazole ( 6 ) that was further degraded into 1 l -(1,2,4/3)-1-hydroxymethyl-2,3,4-cyclohexanetriol (validatol, 25 ) and (2 R ,3 S ,4 S )-2-[(1 R )-1-hydroxyethyl]-pyrrolidine-3,4-diol ( 49 ) by sodium borohydride reduction and subsequent catalytic hydrogenation. Methanolysis of 1 afforded α- and β-glycosides 11 and 10 which were cleaved by hydrogenation to give 25 and methyl α- and β-glycosides of 4-amino-4,6-dideoxy-α- and β- d -glucopyranose (viosamine, 38 ). Upon hydrogenation, 1 gave, beside several minor products, 25 and a basic trisaccharide that was acetolyzed into the peracetates of viosamine 38 and d -glucose. The structure of 6 was determined by derivatives and ring-cleavage products. N.m.r. and mass spectra of the acarbose products and derivatives are discussed.

The development of BAY X 1005 and the Bayer series of leukotriene biosynthesis inhibitors

Leukotrienes represent important inflammatory mediators. The cysteinyl-leukotrienes (Cys-LTs: LTC4, LTD4, LTE4) are assigned to inflammatory allergic conditions like allergic asthma and allergic rhinitis. Besides biochemical and clinical evidence for the smooth muscle contracting effects of Cys-LTs the most obvious evidence comes from experimental and clinical pharmacology to demonstrate the protective role of Cys-LT receptor antagonists and the two classes of inhibitors of leukotriene biosynthesis [1]. These antileukotriene compounds represent the first major breakthrough since many decades of futile research to antagonize the bronchospastic and inflammatory events in allergic asthma.

Drug concentration monitoring, microbial alpha-glucosidase inhibitors, plasminogen activators

Drug Concentration Monitoring.- Microbial Alpha-Glucosidase Inhibitors: Chemistry, Biochemistry and Therapeutic Potential.- Plasminogen Activators: Molecular Properties, Biological Cell Function and Clinical Application.- Author Index Volumes 1-7.