a-Glucosidases are among the most important carbohydrate-splitting enzymes. They catalyze the hydrolysis of a-glucosidic linkages. Their substrates are-depending on their specificity-oligo-and polysaccharides. Microbial inhibitors of a-amylases and other mammalian intestinal carbohydrate-splitting enzymes studied during the last few years have aroused medical interest in the treatment of metabolic diseases such as diabetes. Moreover, they extend the spectrum of microbial secondary metabolites which comprises an enormous variety of structures. They also contribute considerably to a better understanding of the mechanism of action of a-glucosidases. These inhibitors belong to different classes of substances. Those studied most thoroughly are microbial a-glucosidase inhibitors which are members of a homologous series of pseudooligosaccharides of the general formula (4). They all have a core in common which is essential for their inhibitory action, a pseudodisaccharide residue consisting of an unsaturated cyclitol unit, and a 4-amino-4,6-dideoxyglucose unit. The-in many respects-most interesting representative of this homologous series is acarbose (5). a pseudotetrasaccharide exhibiting a very pronounced inhibitory effect on intestinal a-glucosidases such as sucrase, maltase and glucoamylase. The present paper will review this new field of microbial a-glucosidase inhibitors which has been studied with particular intensity during the past ten years. 0 Verlag Chemie GmbH. 6940 Weinheim, 1981 0570-0833/81/0909-0744 $02.50/0 Angew. Chem. lnt. Ed. Engl. 20, 744-761 (1981) [*] K , for I-deoxynojirimycin (36): 4 . 8~ from porcine small intestine, method: "Dixon plot"). mol/L at pH 6.25 (isomaltase Angew. Chem. In(. Ed. Engl. 20. 744-761 (1981)

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The pharmacokinetics of ciprofloxacin (Bay o 9867) was examined after a single oral dose of 250 mg and a single intravenous dose of 100 mg respectively in six healthy male volunteers in an open, randomized crossover study. Although ciprofloxacin concentrations were measured in serum, plasma and urine by HPLC with fluorimetric detection and by microbiological assay, all pharmacokinetic calculations are based on the highly sensitive HPLC method only. The mean serum concentration of ciprofloxacin peaked approximately 1 h after the oral dose (0.94 mg/l). The elimination half-life was about 4 h and the renal clearance was 4.75 ml/min . kg; both were independent of the route of administration. The total clearance (9.62 ml/min . kg) was about twofold higher than the renal clearance. The volume of distribution of the central compartment was calculated to be 0.161 l/kg and the total volume at steady state was 2.0 l/kg. About 27% of the oral dose was excreted in urine, whereas the urinary recovery of the i.v. dose was 46%. The absolute bioavailability of ciprofloxacin was found to be approximately 60%. Ciprofloxacin appears to follow first-order, three compartment model kinetics.

a-Glucosidasen gehoren zu den wichtigsten Kohlenhydrat-abbauenden Enzymen. Sie katalysieren die Hydrolyse a-glucosidischer Bindungen; ihre Substrate sindj e nach Spezifitat -Oligo-und Polysaccharide. Mikrobielle Inhibitoren von a-Amylasen und anderen intestinalen Kohlenhydrat-abbauenden Enzymen von Saugetieren sind bei der Behandlung von Stoffwechselerkrankungen wie Diabetes mellitus von Interesse. Dariiber hinaus erweitern sie das an strukturellen Variationen uberaus reiche Spektrum der mikrobiellen sekundaren Metaboliten, und sie tragen dazu bei, den Wirkungsmechanismus von a-Glucosidasen besser zu verstehen. Diese Inhibitoren gehoren verschiedenen Substanzklassen an. Bisher am besten untersucht sind mikrobielle a-Glucosidasen-Inhibitoren, die Glieder einer homologen Reihe von Pseudooligosacchariden (4) sind. Ihnen gemeinsam ist ein fur die Hemmwirkung essentielles Kernstuck (,,core"), ein Pseudodisaccharidrest, der aus einer ungesattigten Cyclitol-Einheit und einer 4-Amino-4,6-didesoxy-glucose-Einheit besteht. Die in vieler Hinsicht interessanteste Verbindung dieser homologen Reihe ist Acarbose (5), ein Pseudotetrasaccharid mit stark ausgepragter inhibitorischer Wirkung gegenuber intestinalen a-Glucosidasen wie Saccharase, Maltase und Glucoamylase. Dieser Beitrag gibt einen Uberblick uber dieses neue, in den letzten zehn Jahren eingehender bearbeitete Gebiet der mikrobiellen a-Glucosidasen-Inhibitoren.

α‐Glucosidases are among the most important carbohydrate‐splitting enzymes. They catalyze the hydrolysis of α‐glucosidic linkages. Their substrates are—depending on their specificity—oligo‐ and polysaccharides. Microbial inhibitors of α‐amylases and other mammalian intestinal carbohydrate‐splitting enzymes studied during the last few years have aroused medical interest in the treatment of metabolic diseases such as diabetes. Moreover, they extend the spectrum of microbial secondary metabolites which comprises an enormous variety of structures. They also contribute considerably to a better understanding of the mechanism of action of α‐glucosidases. These inhibitors belong to different classes of substances. Those studied most thoroughly are microbial α‐glucosidase inhibitors which are members of a homologous series of pseudooligosaccharides of the general formula (4). They all have a core in common which is essential for their inhibitory action, a pseudodisaccharide residue consisting of an unsaturated cyclitol unit, and a 4‐amino‐4,6‐dideoxy‐ glucose unit. The—in many respects—most interesting representative of this homologous series is acarbose (5), a pseudotetrasaccharide exhibiting a very pronounced inhibitory effect on intestinal α‐glucosidases such as sucrase, maltase and glucoamylase. The present paper will review this new field of microbial α‐glucosidase inhibitors which has been studied with particular intensity during the past ten years.