T. Beetz

Synthesis of a Pentasaccharide Corresponding to the Antithrombin III Binding Fragment of Heparin

Abstract The synthesis of a protected pentasaccharide 27b corresponding to the antithrombin III binding region of heparin is presented. This pentasaccharide was prepared from two disaccharides (12c and 23) and a monosaccharide (1). The glucuronic acid containing disaccharide 12c was prepared from easily available monomers 6 and 7. Oxidation to the uronic acid was performed in the disaccharide stage. L-Idose derivative 16, prepared via a new route, was coupled with 1,6-anhydro derivative 17, oxidized and transformed into disaccharide 23. Coupling of 12c and 23 to tetrasaccharide 24a has been investigated. Better yields were obtained without collidine, the reason for which is explained. Coupling of 24b and 1 afforded the pentasaccharide 27b, protected with acetyl at the positions to be sulphated, benzyl at the other hydroxyl functions and azide at the 2-position of the glucosamine residues. Conversion of 27b into the sulphated pentasaccharide Ib can be performed according to published procedures.

Substituent effects on carbohydrate coupling reactions promoted by insoluble silver salts

Abstract Coupling reactions were performed in the α-D-glucopyranosyl bromide series (i.e. compounds 1 a–c, 2 a, b, 3 and 4 ) and the α-D-mannopyranosyl bromide series (i.e. compounds 7 a–c, 8 a, b, 9 ) with aglycons 5 or 10 in the presence of insoluble silver salt promotors. (i.e. silver silicate and silver zeolite). The insoluble silver salt promotes the formation of the β-glycosidic linkage, while a non-participating group is present at C-2 of the glycon. It was found that in both series 4-O-acyl functions increase the β/α ratio of the glycosidic bond formation relative to 4-O-alkyl functions, whereas 3-O and 6-O-acyl functions decrease this ratio. We assume that inductive effects are responsible for the influence exerted by 3-O-substituents, but that through-bond interactions are essential for the effects exerted by 4-O and 6-O substituents. Another unexpected finding was that coupling of α-D-mannopyranosyl bromide derivatives gave much higher β/α ratios than the corresponding reactions of α -D-glucopyranosyl bromides.

Hydrazinedithiocarbonate (HDTC) as a new reagent for the improved removal of chloroacetyl and bromoacetyl protective groups.

Abstract The use of hydrazinedithiocarbonate (HDTC) for the removal of chloroacetyl and bromoacetyl groups is described. The advantage of this reagent is the selective deprotection under mild conditions, which was demonstrated on carbohydrate derivatives.

Synthesis of a potent antithrombin activating pentasaccharide: A new heparin-like fragment containing two 3-O-sulphated glucosamines

Abstract The synthesis of a pentasaccharide corresponding to the antithrombin III binding region of herapin, but containing an extra 3-O-sulphate group at the reducing end, is described. This compound elicits higher anti-Xa activity than the antithrombin III binding region of heparin.

Synthesis of an antithrombin binding heparin-like pentasaccharide lacking 6-0 sulphate at its reducing end.

Abstract The synthesis of a pentasaccharide of the structure of the antithrombin (AT-III) binding sequence, but lacking the 6-0 sulphate group at the reducing end, is described and its α-Xa activity determined.

Azide Substitution at Mannose Derivatives. A Potential New Route to Glucosamine Derivatives

Abstract Since the pioneering work of Paulsen et al.1 on stereoselective coupling reactions of glucosamine derivatives, the azide function has found general application in carbohydrate chemistry as a nonparticipating masking group for amines. Although excellent results have been reported for the synthesis of α-coupled glucosamine derivatives, the preparation of the required 2-azido-2-deoxy- -glucopyranose is often laborious.1c

An Approach to the Synthesis of Four Rhodomicrobium Vannielii Lipid a Analogues

Abstract The preparation of four Rh. Vannielii Lipid A analogues (i.e. compounds 22, 23, 30 and 33) is described. Non-neighbouring group supported introduction of the β-glycosidic linkages was performed by coupling the mannopyranosyl bromide 2 and the 2-azido-2-deoxy-glucopyranosyl bromides 10 and 13 with the suitably protected glycosyl acceptors 3, 4 and 5 in the presence of a heterogeneous silver catalyst, to give compounds 6, 7, 14 and 24, respectively. Selective removal of the ally1 group and reduction of the azido functions followed by several O,N-acylation steps afforded, after complete deblocking, the tri-and disaccharide Rh. Vannielii Lipid A analogues 22, 23, 30 and 33.