US 4,056,322 A · Preparation of ethers of monosaccharides

Abstract

Ethereally substituted monosaccharides are prepared from certain selectively derivatized monosaccharides. In practicing the method: 1. a monosaccharide derivative having the general formula A.sub.1 -O-H, wherein O is oxygen, H is hydrogen and A.sub.1 is the residue of a monosaccharide selected from the group consisting of pentoses, hexoses and heptoses which has been derivatized with at least one substance selected from the group consisting of (1-a) at least one aliphatic alcohol containing 1-18 carbon atoms to produce an hydrolyzable acetal group at the site of at least one available hydroxyl residue, (1-b) at least one aldehyde containing 1-18 carbon atoms to produce at least one hydrolyzable acetal group at the site of at least one available hydroxyl residue, (1-c) at least one ketone containing 1-18 carbon atoms to produce at least one hydrolyzable ketal group at the site of at least one available hydroxyl residue, and (1-d) at least one organic acid residue containing 1-18 carbon atoms to produce an hydrolyzable ester group at the site of at least one available hydroxyl residue; is reacted with 2. an organic halide having the general formula Y - X, wherein X is selected from the group consisting of chlorine, bromine and iodine and Y is selected from the group consisting of (2-a) cyclic monovalent nitrogen containing organic radicals and residua, and (2-b) monovalent organic radicals and residue having the general formula -R.sub.1 B wherein B is selected from the group consisting of ##STR1## --O--R.sub.4 and --S--R.sub.4, R.sub.1 is a divalent organic radical having a linear carbon chain length of about 1-7 carbon atoms, R.sub.2 and R.sub.3 are selected from the group consisting of --H,--OH, --SH, halogen and monovalent organic radicals and residua having a linear carbon chain length of about 1-7 carbon atoms, R.sub.4 is selected from the group consisting of --H and monovalent organic radicals and residua having a linear carbon chain length of about 1-7 carbon atoms, N is nitrogen, O is oxygen, S is sulfur and H is hydrogen; To produce an ethereally substituted monosaccharide derivative having the general formula A-O-Y wherein A, Y and O are as above defined. The monosaccharide derivative (1) and the organic halide (2) are reacted at an elevated reaction temperature while dissolved in a substantially anhydrous organic solvent in the presence of a solid substantially anhydrous strong inorganic base of a metal selected from the group consisting of the alkali metals and the alkaline earth metals. The resultant ethereally substituted monosaccharides may be partially or fully hydrolyzed in an aqueous acidic medium. In one preferred variant, 1,2:5,6-di-O-isopropylidene 3-O-3'-(N',N'-dimethylamino-n-propyl)-D-glucofuranose is prepared and, when desired, thereafter partially or fully hydrolyzed to produce 1,2-O-isopropylidene-3-O-3'-(N',N'-dimethylamino-n-propyl)-D-glucofuranose or 3-O-3'-(N'-N'-dimethylamino-n-propyl-D-glucose in the free amine and/or salt forms. The method is capable of preparing the ethereally substituted monosaccharides in high yield and purity with a minimum of side products. The resultant compounds exhibit striking antiviral activity and/or have other therapeutically valuable properties and are useful in the treatment of warm-blooded animals.

Claims20

Dependent claims

In a method of preparing an ethereally substituted monosaccharide comprising the step of reacting

1. a monosaccharide derivative having the general formula A-O-H, wherein O is oxygen, H is hydrogen and A is the residue of a monosaccharide selected from the group consisting of pentoses, hexoses and heptoses which has been derivatized with at least one substance selected from the group consisting of (1-a) at least one alcohol containing 1-18 carbon atoms to produce an acetal group at the site of at least one available hydroxyl residue. (1-b) at least one aldehyde containing 1-18 carbon atoms to produce at least one acetal group at the site of at least one available hydroxyl residue, (1-c) at least one ketone containing 1-18 carbon atoms to produce at least one ketal group at the site of at least one available hydroxyl residue, and (1-d) at least one organic acid residue containing 1-18 carbon atoms to produce an ester group at the site of at least one available hydroxyl residue, the said hydrolyzable acetal groups (1-a) and (1-b), ketal group (1-c) and ester group (1-d) being removable from said A by hydrolysis in an acidic aqueous medium having a pH value less than 7,
2. an organic halide having the general formula Y-X, wherein X is selected from the group consisting of chlorine, bromine and iodine and Y is selected from the group consisting of (2-a) cyclic monovalent nitrogen containing organic radicals and residua free of carbonyl oxygen and (2-b) monovalent organic radicals and residua having the general formula --R.sub.1 --B, wherein B is selected from the group consisting of ##STR5## --O--R.sub.4 and --S--R.sub.4, R.sub.1 is a divalent organic radical having a linear carbon chain length of about 1-7 carbon atoms, R.sub.2 and R.sub.3 are selected from the group consisting of --H, --OH, --SH, halogen and monovalent organic radicals and residua having a linear carbon chain length of about 1-7 carbon atoms, R.sub.4 is selected from the group consisting of --H and monovalent organic radicals and residua having a linear carbon chain length of about 1-7 carbon atoms, N is nitrogen, O is oxygen, S is sulphur and H is hydrogen,
the said hydrogen atom H of the monosaccharide derivative A-O-H and the said halogen atom X of the organic halide being reactive whereby the said H is replaced by Y to produce an ethereally substituted monosaccharide derivative having the general formula A-O-Y wherein A and Y are as above defined,
the improvement which comprises reacting said monosaccharide derivative (1) and the said organic halide (2) at an elevated reaction temperature below the thermal decomposition temperature thereof while dissolved in an anhydrous organic solvent in the present of a solid anhydrous strong inorganic base of a metal selected from the group consisting of the alkali metals and the alkaline earth metals and in the presence of a dehydrating agent which is a scavenger for water whereby anhydrous reaction conditions are maintained throughout the reaction.

1 more element

In a method of preparing an ethereally substituted monosaccharide comprising the steps of reacting

1. a monosaccharide derivative having the general formula A.sub.1 -O-H, wherein O is oxygen, H is hydrogen and A.sub.1 is the residue of a monosaccharide selected from the group consisting of pentoses, hexoses and heptoses which has been derivatized with at least one substance selected from the group consisting of (1-a) at least one alcohol containing 1-18 carbon atoms to produce a hydrolyzable acetal group at the site of at least one available hydroxyl residue, (1-b) at least one aldehyde containing 1-18 carbon atoms to produce at least one hydrolyzable acetal group at the site of at least one available hydroxyl residue, (1-c) at least one ketone containing 1-18 carbon atoms to produce at least one hydrolyzable ketal group at the site of at least one available hydroxyl residue, and (1-d) at least one organic acid residue containing 1-18 carbon atoms to produce a hydrolyzable ester group at the site of at least one available hydroxyl residue, the said hydrolyzable acetal groups (1-a) and (1-b), ketal group (1-c) and ester group (1-d) being removable from said A.sub.1 by hydrolysis in an acidic aqueous medium having a pH value less than 7, with
2. an organic halide having the general formula Y-X, wherein X is a halogen atom selected from the group consisting of chlorine, bromine and iodine and Y is selected from the group consisting of (2-a) cyclic monovalent nitrogen containing organic radicals and residua free of carbonyl oxygen, and (2-b) monovalent organic radicals and residua having the general formula --R.sub.1 --B, wherein B is selected from the group consisting of ##STR7## --O--R.sub.4 and --S--R.sub.4, R.sub.1 is a divalent organic radical having a linear carbon chain length of about 1-7 carbon atoms, R.sub.2 and R.sub.3 are selected from the group consisting of --H,--OH, --SH, halogen and monovalent organic radicals and residua having a linear carbon chain length of about 1-7 carbon atoms, R.sub.4 is selected from the group consisting of --H and monovalent organic radicals and residua having a linear carbon chain length of about 1-7 carbon atoms, N is nitrogen, O is oxygen, S is sulfur and H is hydrogen,
the said hydrogen atom H of the monosaccharide derivative A.sub.1 -O-H and the said halogen atom X of the organic halide being reactive whereby the said H is replaced by Y to produce an ethereally substituted monosaccharide derivative having the general formula A.sub.1 -O-Y wherein A.sub.1, Y and O are as above defined,
the improvement which comprises reacting said monosaccharide derivative (1) and the said organic halide (2) at an elevated reaction temperature below the thermal decomposition thereof while dissolved in an anhydrous organic solvent in the presence of a solid anhydrous strong inorganic base of a metal selected from the group consisting of the alkali metals and the alkaline earth metals,
separating the said ethereally substituted monosaccharide derivative having the general formula A.sub.1 -O-Y from the reaction mixture, and
removing at least one but not all of said acetal, ketal or ester groups from A.sub.1 by partial hydrolysis in an acidic aqueous medium having a pH value of about 3-6 to produce an ethereally substituted monosaccharide having the general formula A.sub.2 -O-Y, wherein O and Y are as above defined and A.sub.2 is the residue of a monosaccharide corresponding to A.sub.1 as above defined with at least one but not all of said acetal, ketal or ester groups being removed therefrom.

3 more elements

Dependencies are inferred from the claim text.

Preparation of ethers of monosaccharides

Life of this patent

Preparation of ethers of monosaccharides

Life of this patent

Abstract

Claims20