In the reactions used to break heparin down to mono- and oligosaccharides, androsugars are formed at two stages. The first of these is the well-known cleavage of heparin with nitrous acid to convert the N-sulfated D-glucosamines to anhydro-D-mannose residues; this reaction has been studied in detail. It is demonstrated here that only low pH (less than 2.5) reaction conditions favor the deamination of N-sulfated D-glucosamine residues; the reaction proceeds very slowly at pH 3.5 or above. On the other hand, N-unsubstituted amino sugars are deaminated at a maximum rate at pH 4 with markedly reduced rates at pH2 or pH6. At room temperature solutions of nitrous acid lose one-fourth to one-third of their capacity to deaminate amino sugars in 1 h at all pHs. A low pH nitrous acid reagent which will convert heparin quantitatively to its deamination products in 10 min at room temperature is described, and a comparison of the effectiveness of this reagent with other commonly used nitrous acid reagents is presented. It is also shown that conditions used for acid hydrolysis of heparin convert approximately one-fourth of the L-iduronosyluronic acid 2-sulfate residues to a 2,5-anhydrouronic acid. This product is an artifact of the reaction conditions, and its formation represents one of several pathways followed in the acid-catalyzed cleavage of the glycosidic bond of the sulfated L-idosyluronic acid residues.

Formation of anhydrosugars in the chemical depolymerization of heparin.

Publisher Summary This chapter discusses the important reactions of the hydroxyl group. Knowledge of the relative reactivities of hydroxyl groups in carbohydrates is fundamental to a thorough understanding of carbohydrate chemistry. The chapter explains esterification, which forms the largest part of the literature since 1953 on selective reactions of carbohydrates. The common methods of esterification utilize an acid chloride or an acid anhydride as the reagent, but other acid derivatives often show different selectivities. An investigation pertinent to the subject of favored reactivity concerned the reactions of certain acyl halides with ethanol, in acetone or chloroform solution. The mixed-order nature of some of these reactions suggested that every rate-determining transition-state contained the substrate, the nucleophile (ethanol), and an acceptor— X—for hydrogen bonding, suitable acceptors being an acetone molecule, a chloride ion, or another ethanol molecule. The possibility that intramolecular hydrogen-bonding does not persist in pyridine and that the advantage of a bonded hydroxyl group would be lost, invalidates the explanation of favored reactivity. But if the hydrogen-bonding to pyridine is hindered in the transition state, intramolecular hydrogen-bonding could conceivably assume importance.

Relative Reactivities of Hydroxyl Groups in Carbohydrates

The present invention relates to compounds, methods and pharmaceutical compositions for inhibiting proteases, particularly serine proteases, and more particularly HCV NS3 proteases. The compounds, and the compositions and methods that utilize them, can be used, either alone or in combination to inhibit viruses, particularly HCV virus.

Inhibitors of serine proteases, particularly hepatitis C virus NS3 protease

Publisher Summary This chapter discusses copper complexes that offer a physiological approach to the treatment of chronic diseases. Copper is recognized as an essential metalloelement just as sodium, potassium, magnesium, calcium, iron, zinc, chromium, vanadium, and manganese. Just as essential amino acids, essential fatty acids and essential cofactors (vitamins), essential metalloelements are required for normal metabolic processes but cannot be synthesized de novo, and daily dietary intake and absorption are required. The adult body contains between 1.4 mg (22 pmol) and 2.1 mg (33 pmol) of copper per kilogram of body weight while the infant body contains three times this amount, consistent with the fact that infant metabolic needs are that much greater than those of adults. The essentiality of copper is now understood as being based upon its recognized need for activation of copper-dependent enzymes. Complexed forms of copper also facilitate absorption, tissue distribution, and tissue utilization. In the nondisease state, these forms of copper account for the physiologic regulation of copper-dependent homeostatic processes. Consistent with the newly found role for copper in synthesis of neuroendocrine peptides, the copper complex of histidine has been found to increase the secretion of luteinizing hormone-releasing hormone (LH-RH) from granules of the median eminence.

Copper complexes offer a physiological approach to treatment of chronic diseases.

Chemistry of Bridged Lactams and Related Heterocycles

d-Idose aus d(+)-Galaktose

Eine Reihe von Verbindungen, die fahig sind, Metalle komplex zu binden, wird auf ihre tuberkulostatische Wirkung untersucht. Es zeigt sich, dass bei einigen in vitro und beim 5-Oxychinoxalin auch in vivo durch Cu‥ eine. Steigerung der Aktivitat zu erzielen ist.

Über die Beeinflussung tuberkulostatischer Wirkungen durch Cu‥. Metallionen und biologische Wirkung, 7. Mitteilung

Die Ionen der Alkali- und der Erdalkali-Gruppe wurden als Acetate mit einem Gemisch von Athylalkohol-Essigsaure aufsteigend chromatographiert. Die getrennten Ionen konnen in unterschiedlich gefarbte Violurate ubergefuhrt werden. Es werden die Rf-Werte fur Li., Na., K., Be‥, Mg‥, Ca‥, Sr‥, Ba‥ ermittelt.

Eine papierchromatographische Trennung und Bestimmung der Alkali‐ und Erdalkali‐Ionen

Es wird eine einfache Methode zur Darstellung der p-Aminosalicylsaure angegeben. Zur Prufung der biologischen Strukturspezifitat dieser Verbindung wird eine Reihe von strukturahnlichen Verbindungen hergestellt und auf ihre tuberkulostatische Wirksanikeit gepruft.

Zur Kenntnis der p‐Amino‐salicylsäure und strukturähnlicher Verbindungen

Es wird uber die Eigenschaften einiger nach verschiedenen Methoden hergestellter α-Aminoketone berichtet. Die Verbindungen zeigen z. T. im Regenerationstest an der Xenopuslarve eine bemerkenswerte Aktivitat.

E. Sorkin

Papers

d-Idose aus d(+)-Galaktose

Über die Beeinflussung tuberkulostatischer Wirkungen durch Cu‥. Metallionen und biologische Wirkung, 7. Mitteilung

Eine papierchromatographische Trennung und Bestimmung der Alkali‐ und Erdalkali‐Ionen

Zur Kenntnis der p‐Amino‐salicylsäure und strukturähnlicher Verbindungen

Über die chemischen und biologischen Eigenschaften einiger α‐Aminoketone