Glycosidic derivatives

Details Glycosidic derivatives Glycosidic derivatives

1986-09-03

1989-09-19

Rollins, John W.

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

536 5, 536 172, 536 175, 536 176, 536 177, 536 178, 536 179, 536 182, 536 184, C07H 1504, C07H 1518, A61K 3170, A61K 31705

Patent

active

048682896

DESCRIPTION:

BRIEF SUMMARY
BACKGROUND OF THE INVENTION

1. Field of the Invention
The present invention relates to novel glycosides and glycoconjugates useful as i.a. synthetic biological receptors.
2. Description of the Prior Art
Natural glycoconjugates consist of a carbohydrate portion, which is, in most cases, coupled to a lipid or a protein (cf. Hakomori (1981) and Sharon & Lis (1981)). In most of the glycolipids, the sugar is coupled to either the fatty amino alcohol sphingosine or to glycerol, which in turn are transformed into fatty acid derivatives. The general structures of these two types of glycolipids are shown below.


__________________________________________________________________________ NATURAL GLYCOLIPIDS __________________________________________________________________________ ##STR1## GLYCOSPHINGO- LIPID ##STR2## GLYCOGLYCERO- __________________________________________________________________________ LIPID acid in a protein. Glycolipids and glycoproteins are integral parts of the plasma membranes of mammalian cells. Some of these glycoconjugates function i.a. as specific receptors towards a variety of biological entities. The carbohydrate part of the glycoconjugate is exposed on the outside of the plasma membrane, and it may consequently exhibit antigenic properties. This is the basis for the various blood-group systems (cf. Lemieux (1978)). It has recently been shown that membrane-carbohydrates of the above type are important as receptors for proteins (cf. Sharon & Lis (1972) and Kabat (1980)) like lectines, antibodies and hormones and for anchoring microorganisms to cell surfaces (cf. Beachey (1981)).
Unnatural glycoconjugates (so-called neo-glycoconjugates) have been prepared both as neo-glycolipids (cf. Slama & Rando (1980) and Dahmen et al. (Carbohydr. Res., 127, 1984)) and neo-glycoproteins (cf. Lemieux et al. (1975) and Dahmen et al. (Carbohydr. Res., 129, 1984)). No neo-glycolipids having a close molecular similarity to the natural compound have, however, yet been prepared. It is known (cf. Israelachvili et al. (1980)) that the chemical structure of the hydrophobic part of lipids determines the type of aggregates that can be formed (micelles, liposomes, etc.) and also the kind of influence that a lipid will have when it is incorporated into e.g. a cellular membrane. In view of the high receptor specificity and biological importance of carbohydrate complexes it is obvious that there is a great need for molecularly well defined, easily prepared glycoconjugates for use in therapy, prophylaxis, and diagnosis as well as in biochemical research.


SUMMARY OF THE INVENTION

One object of the present invention is to provide novel O-glycosidic compounds useful for therapy or prophylaxis of a wide variety of diseases, for diagnostic use or as research chemicals.
Another object of the present invention is to provide a method for preparing the novel O-glycosidic compounds.
Thus, the invention relates to O-glycosidic compounds of the formula I ##STR3## wherein
n is an integer from 1 to 10, inclusive, and Sugar is selected from the group consisting of D-glucose, D-galactose, D-mannose, D-xylose, D-ribose, D-arabinose, L-fucose, 2-acetamido-2-deoxy-D-glucose, 2-acetamido-2-deoxy-D-galactose, D-glucuronic acid, D-galacturonic acid, D-mannuronic acid, 2-deoxy-2-phthalimido-D-glucose, 2-deoxy-2-phthalimido-D-galactose and sialic acid, and derivatives thereof whereby, when n>1, the Sugar units may be the same or different; and ##STR4## wherein m and p independently are 0 or 1 and m+p is 0, 1 or 2, of 1-25 carbon atoms, aryl or a steroid group, and R.sub.10 is C.sub.1-4 -alkyl or a carrier, CONHNH.sub.2, CON.sub.3, CH(OR.sub.10).sub.2 wherein R.sub.10 is as defined above, or a carrier, are as defined above, ##STR5## wherein R.sub.7 and R'.sub.7, which may be the same or different, are the same as R.sub.6 defined above; or are as defined above, above, as defined above, formula I, the polymers having
(1) the formula XX ##STR6## wherein Sugar, n, and R.sub.4 are as defined above, and k is an i

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