GB1574073A - Amino-alkylglycosides and their sulphur and nitrogen analogues - Google Patents

Description

(54) AMINOALKYLGLYCOSIDES AND THEIR SULFUR AND NITROGEN ANALOGUES (71) We, MERCK & CO. INC., a corporation duly organized and existing under the laws of the State of New Jersey, United States of America, of Rahway, New Jersey, United States of America, do hereby declare the invention for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- This invention relates to 1 - deoxy - glycopyranosides.

The invention provides novel 1 - (w - aminoalkyl)glycopyranosides and 1 deoxy - analogs thereof having a 1 - (a) - aminoalkylthio) or 1 - amino - alkanoylamino) substituent. These compounds may be represented, in the case of the preferred 1 - substituted - D - manno - pyranosides, by the following formula:

where Z is oxy, thio or NHCO; and x is an integer from 2 to 8. It has been found that 1 - (a) - aminoalkyl) - glycopyranosides, I - [( - aminoalkyl)thio] - I deoxy - glycopyranosides, and I - [( - aminoalkanoyl)amino] - 1 - deoxy glycopyranosides of this invention possess biological activity characteristic of the action of insulin.

These 1 - substituted glycopyranosides are conveniently prepared utilizing, as starting material, a tetra - 0 - acetyl - glycopyranosyl bromide in the case of the 1 (c.) - aminoalkyl)glycopyranosides, an alkali metal glycopyranosyl mercaptide (i.e.

a 1 - thio - hexose alkali metal salt) or tetra - 0 - acetyl - glycopyranosyl bromide in the case of the 1 - [( - aminoalkyl)thio] - 1 - deoxy - glycopyranosides, or a tetraacetyl - glycopyranosylamine in the case of the 1 - [(a) - aminoalkanoyl)amino] - 1 - deoxy - glycopyranosides.

The 1 - (a) - aminoalkyl)- glycopyranosides are ordinarily prepared by reacting the corresponding tetra - 0 - acetyl - glycopyranosyl bromide, such as 2,3,4,6 - tetra - O - acetyl - a - D - mannopyranosyl bromide, 2,3,4,6 - tetra O - acetyl - a - D - glucopyranosyl bromide or 2,3,4,6 - tetra - 0 - acetyl - a D- galactopyranosyl bromide, with an a) - (benzyloxycarbonylamino) - 1 - alkanol, such as 5 - (benzyloxycarbonylamino) - I - pentanol, 6 (benzyloxycarbonylamino) - 1 - hexanol or 7 - (benzyloxycarbonylamino) heptanol. to form the corresponding 1 - (c9 - benzyloxycarbonylamino - alkyl) tetra - 0 - acetyl - glycopyranoside, such as I - (5 - benzyloxycarbonylamino pentyl)- 2,3,4,6 - tetra - 0 - acetyl - a - D - mannopyranoside, 1 - (6 - benzyloxycarbonylamino - hexyl) - 2,3,4,6 - tetra- O- acetyl- a - D - mannopyranoside, 1 - (6 - benzyloxycarbonylamino - hexyl) - 2,3,4,6 - tetra O - acetyl - - D - glucopyranoside, 1 - (6 - benzyloxycarbonylamino - hexyl) 2,3,4,6 - tetra - 0 - acetyl - ssB- D- galactopyranoside or 1 - (7 - benzyloxycarbonylamino - heptyl)- 2,3,4,6 - tetra - 0 - acetyl - a - D - mannopyranoside. The reaction is preferably conducted by bringing the reactants together in a substantially anhydrous polar organic solvent such as nitromethane, or mixture of nitromethane and benzene, in the presence of mercuric cyanide catalyst, as well as a dehydrating agent such as anhydrous calcium sulfate to ensure the maintenance of anhydrous conditions during the reaction, and stirring the resulting mixture at room temperature for a period of approximately 15 hours, at the end of which time the reaction is substantially complete. The reaction mixture is ordinarily evaporated to dryness, extracted with a water-immiscible organic solvent such as chloroform, and the chloroform-soluble material is subjected to chromatography over silica gel to give the 1 - ( - benzyloxycarbonylamino alkyl) - tetra - 0 - acetyl - glycopyranoside in substantially pure form.

This compound is then reacted, in solution in a C16 alkanol such as methanol, with an alkali metal alkoxide such as sodium methoxide, at substantially room temperature for a period of approximately two hours, thereby transesterifying the acetyl groupings to form the corresponding I - ( - benzyloxycarbonylaminoalkyl) - glycopyranoside. In practice the slightly alkaline transesterification mixture is neutralized by stirring with an acidic resin, the resin is separated by filtration, and the filtrate is evaporated to give the 1 - (a) - benzyloxycarbonylamino - alkyl)glycopyranoside, such as 1 - (5 benzyloxycarbonylamino - pentyl)- a - D - mannopyranoside, 1 - (6 - benzyloxycarbonylamino - hexyl) - a - D- mannopyranoside, 1 - (6 - benzyloxycarbonylamino - hexyl) - 6 - D - glucopyranoside, 1 - (6 - benzyloxycarbonylamino - hexyl) - A- D - galacto - pyranoside or 1 - (7 - benzyloxycarbonylamino - heptyl) - a - D - mannopyranoside.

The I - (a) - benzyloxycarbonylamino - alkyl)glycopyranoside is then reacted with hydrogen, thereby removing the benzyloxycarbonyl grouping. The hydrogenation reaction is conveniently conducted by dissolving the 1 - (- - benzyloxycarbonylamino - alkyl)glycopyranoside in an aqueous alkanol, such as methanol, adding palladium-on-carbon-catalyst, and vigorously agitating the mixture at about 25"C in contact with hydrogen at atmospheric pressure, under which conditions the hydrogenation reaction is substantially complete in about one hour, to form the corresponding 1 - ( - aminoalkyl) - glycopyranoside. The latter is conveniently recovered from the hydrogenation reaction mixture by filtering the mixture through diatomaceous silica, and subjecting the filtered solution to chromatography on a silica gel column to give, in substantially pure form, the 1 (a) - aminoalkyl) - glycopyranoside, such as I - (5 - aminopentyl) - a - D - mannopyranoside, 1 - (6 - aminohexyl) - a - D - mannopyranoside, 1 - (6 - aminohexyl) - 6 - D - glucopyranoside, 1 - (6 - aminohexyl) - 6 - D - galactopyranoside or 1 - (7 - aminoheptyl) - a - D - mannopyranoside.

The I - [( - aminoalkyl)thio] - 1 - deoxy - glycopyranosides are ordinarily prepared by reacting the corresponding tetra - 0 - acetyl - glycopyranosyl bromide, such as 2,3,4,6 - tetra - 0 - acetyl - a - D - mannopyranosyl bromide, 2,3,4,6 - tetra - 0 - acetyl - a - D - glucopyranosyl bromide or 2,3,4,6 - tetra O - acetyl - a - D - galactopyranosyl bromide, with thiourea in solution in a substantially anhydrous polar organic solvent such as anhydrous acetone to form the corresponding tetra - 0 - acetyl - 1 - deoxy - glycopyranosyl isothiouronium bromide. The reaction is preferably conducted by heating the anhydrous mixture of the tetra - 0 - acetyl - glycopyranosyl bromide, thiourea, and anhydrous acetone at reflux temperature, under which conditions the reaction is ordinarily complete in about two hours. The reaction mixture is cooled and evaporated to dryness in vacuo, and the residual material is crystallized from cold water or acetone to give the said tetra - 0 - acetyl - 1 - deoxy glycopyranosylisothiouronium bromide, such as 2,3,4,6 - tetra - 0 - acetyl - 1 deoxy - a - D - mannopyranosylisothiouronium bromide, 2,3,4,6 - tetra - 0 acetyl - 1 - deoxy - p - glucopyranosylisothiouronium bromide or 2,3,4,6 - tetra O - acetyl - I - deoxy - ,B - D - galacto - pyranosylisothiouronium bromide.

The tetra - 0 - acetyl - 1 - deoxy - glycopyranosyl - isothiouronium bromide is reacted with 1 - iodo - e) - trifluoroacetylamino - alkane, such as 1 iodo - 5 - trifluoroacetylamino - pentane, I - iodo - 6 - trifluoroacetylamino hexane or 1 - iodo - 7- trifluoroacetylamino - heptane. The reaction is conveniently conducted by bringing together an aqueous solution of tetra - 0 acetyl - 1 - deoxy - glycopyranosylisothiouronium bromide containing potassium carbonate and potassium metabisulfite, and an acetone solution containing I iodo - # - trifluoroacetylamino - alkane, and vigorously agitating the resulting mixture at approximately 250C, under which conditions the reaction is ordinarily complete in about thirty minutes. The acetone is then evaporated, the residual aqueous mixture is extracted with a water-immiscible organic solvent such as chloroform, and the chloroform extract is evaporated to dryness. The residual material is recrystallized from a C16 alkanol such as ethanol to give the corresponding 1 - [(w - trifluoroacetylaminoalkyl)thio] - tetra - O - acetyl - I - deoxy - glycopyranoside, such as 1 - [(5 - trifluoroacetylamino - pentyl)thio] 2,3,4,6 - tetra - O - acetyl - 1 - deoxy - a - D - mannopyranoside, 1 - [(6 trifluoroacetylamino - hexyl)thio] - 2,3,4,6 - tetra - O - acetyl - I - deoxy - a D - mannopyranoside, 1 - [(6 - trifluoroacetylamino - hexyl)thio] - 2,3,4,6 - tetra - O - acetyl - 1 - deoxy - ,B- D- glucopyranoside, 1 - [(6 - trifluoroacetylamino - hexyl)thio] - 2,3,4,6 - tetra - O - acetyl - 1 - deoxy - ss d - galacto-pyranoside or 1 - [(7 - trifluoroacetylamino - heptyl)thio] - 2,3,4,6 tetra - 0 - acetyl - 1 - deoxy - a - d - mannopyranoside.

Alternatively, a mixture of 1 - Yhio - hexose salt, e.g. an alkali metal glycopyranosyl mercaptide such as 1 - thio - a - D - mannose sodium salt, 1 thio - ss - D - mannose sodium salt, 1 - thio - p - D - galactose sodium salt, or 1 thio - ss - D - glucose sodium salt, is reacted with a 1 - iodo - a) trifluoroacetylamino - alkane, such as I - iodo - 5- trifluoroacetylamino pentane, 1 - iodo - 6- trifluoroacetylamino - hexane, or 1 - iodo - 7 trifluoroacetylamino - heptane and then acylated. The first step is carried out by heating with stirring at a temperature of about 50"C, in an aqueous alcohol, such as aqueous ethanol, under which conditions the reaction is ordinarily complete in about one hour. The reaction mixture is evaporated to dryness, the residual material is acetylated with acetic anhydride and pyridine, and the acetylated mixture is codistilled with toluene, thereby removing pyridine, unreacted acetic anhydride and by-product acetic acid. The residual material is partitioned between dichloromethane and water to give the corresponding I - [( - trifluoroacetylamino - alkyl)thioi - tetra - 0 - acetyl - 1 - deoxy glycopyranoside.

The 1 - [(a) - trifluoroacetylamino - alkyl)thio]tetra- O- acetyl- 1 - deoxy - glycopyranoside, produced by either of the above two methods, is then reacted in aqueous ethanolic solution with a strongly basic anion-exchange resin on the hydroxyl cycle, said resin preferably comprising quaternary ammonium groups attached to a styrene-divinyl-benzene copolymer. In practice the reaction mixture is stirred vigorously at a temperature of about 25 C, under which conditions hydrolysis of the acetyl and trifluoroacetyl groupings is ordinarily complete in about 15 hours. The insoluble resin is separated from the reaction mixture by filtration, washed with an organic solvent such as methanol, and the solvents evaporated from the combined filtrate and washings to give a syrup which ordinarily crystallizes upon standing to give the corresponding 1 - [(w - aminoalkyl)thio] - 1 - deoxy - glycopyranoside, such as 1 - [(5 - aminopentyl)thioi - 1 - deoxy - a - D - mannopyranoside, 1 - [(6 - aminohexyl)thio] - 1 - deoxy - a- D - mannopyranoside, 1 - [(6 aminohexyl)thio] - 1 - deoxy - p- D- mannopyranoside, 1 - [(6 aminohexyl)thio] - 1 - deoxy - A- D - glucopyranoside, 1 - [(6 - aminohexyl)thio] - 1 - deoxy - ss - D - galactopyranoside or 1 - [(7 aminoheptyl)thioi - I - deoxy - p - D - mannopyranoside.

If desired, tetra - 0 - acetyl - 1 - deoxy - glycopyranosyl - isothiouronium bromide may be reacted with a a) - iodo - 1 - alkanol, such as 5 - iodo - 1 pentanol or 6 - iodo - I - hexanol. This reaction, which may be carried out in a manner analogous to that of the hereinabove described reaction, which uses 1 iodo - a) - trifluoroacetylamino - alkane in place of the # - iodo - I - alkanol, results in the formation of the corresponding I - [(cl) - hydroxyalkyl)thio] - tetra 0 - acetyl - 1 - deoxy - glycopyranoside, such as I - [(5 - hydroxypentyl)thio] 2,3,4,6 - tetra - O - acetyl - 1 - deoxy - a - D - mannopyranoside, 1 - [(6 - hydroxyhexyl)thio] - 2,3,4,6 - tetra - 0 - acetyl - I - deoxy - a - D mannopyranoside, 1 - [(6 - hydroxyhexyl)thio] - 2,3,4,6 - tetra - 0 - acetyl - I - deoxy - ss - D - glucopyranoside or 1 - [(6 - hydroxyhexyl)thio] - 2,3,4,6 - tetra O - acetyl - 1 - deoxy - B - D - galactopyranoside.

The 1 - [(#- hydroxyalkyl)thio] - tetra - 0 - acetyl - 1 - deoxy - glycopyranoside is then reacted with p - toluene - sulfonylchloride in the presence of a base such as pyridine thereby forming the corresponding p - toluene sulfonate. The reaction is conveniently conducted by dissolving the 1 - [(# hydroxyalkyl)thio] - tetra - 0 - acetyl - 1 - deoxy - glycopyranoside in dry pyridine, adding to this solution a solution of an equivalent amount of p - toluene sulfonylchloride in an organic solvent such as chloroform, and stirring the resulting mixture at a temperature of about 0 C, under which conditions the esterification reaction is ordinarily complete in about four hours. The reaction mixture is then poured into ice water, and the aqueous mixture extracted with a water-immiscible organic solvent such as dichloromethane. The combined dichloromethane extracts are washed with an aqueous bicarbonate solution to remove acidic materials, and the organic layer is dried and subjected to vacuum codistillation with toluene to remove pyridine. The residual material is purified by chromatography to give the corresponding I - [( - p - toluenesulfonyloxy - alkyl)thioi - tetra - O - acetyl - 1 - deoxy - glycopyranoside such as 1 - [(5- p- toluenesulfonyloxy pentyl)thio] - 2,3,4,6 - tetra - O - aeetyl - I - deoxy - a - D - mannopyranoside, 1 - [(6 - p - toluenesulfonyloxy - hexyl)thio] - 2,3,4,6 - tetra - O - aeetyl - 1 - deoxy - a - D - mannopyranoside, 1 - [(6 - p - toluenesulfonyloxy - hexyl)thiol 2,3,4,6 - tetra - 0 - acetyl - 1 - deoxy - ss - D - glucopyranoside or 1 - [(6 - p toluenesulfonyloxy - hexyl)thio] - 2,3,4,6 - tetra - O - acetyl - 1 - deoxy - ss - D - galactopyranoside.

This I - [( - p - toluenesulfonyloxy - alkyl)thioi - tetra - O - acetyl - 1 - deoxy - glycopyranoside, is then reacted with sodium cyanide in dimethyl formamide solution, preferably by heating it with an equivalent of sodium cyanide and an amount of dimethylformamide equal to about ten times the combined weight of the other two reactants with stirring at a temperature of about 45 C while maintaining the mixture under substantially anhydrous conditions; the replacement of the p - toluenesulfonyloxy substituent by the cyano group is ordinarily complete in approximately four hours. The reaction mixture is poured into ice-water, the aqueous mixture is extracted with a water-immiscible organic solvent such as dichloromethane, and the dichloromethane extracts are washed with water, dried, and evaporated to dryness. The residual material is acetylated with excess of acetic anhydride - pyridine and the acetylated product is purified by chromatography to give the corresponding 1 - [(w - cyanohexyl)thio] - tetra - 0 - acetyl - I deoxy - glycopyranoside, such as 1 - [(5 - cyanopentyl)thio] - 2,3,4,6 - tetra - O acetyl - 1 - deoxy - a - D - mannopyranoside, 1 - [(6 - cyanohexyl)thio] 2,3,4,6 - tetra - O - acetyl - 1 - deoxy - α - D - mannopyranoside, 1 - [(6 - cyanohexyl)thio] - 2,3,4,6 - tetra - 0 - acetyl - 1 - deoxy - P- Dglucopyranoside or 1 - [(6 - cyanohexyl)thio] - 2,3,4,6 - tetra - 0 - acetyl - 1 deoxy - ss - D - galactopyranoside.

The acetyl groups are removed from this 1 - [( - cyanohexyl)thio] - tetra O - acetyl - 1 - deoxy - glycopyranoside by reaction with a catalytic amount of alkali metal alkoxide in a C16 alcohol, e.g. in dry methanol at a temperature of 25 C with a catalytic amount of sodium methoxide, under which conditions the deacetylation reaction is ordinarily complete in about two hours. In practice the reaction solution is then neutralized by sitrring with an acidic resin, the resin removed by filtration, and the filtrate evaporated to give the corresponding 1 [(a) - cyanohexyl)thioi - 1 - deoxy - glycopyranoside, such as 1 - [(5cyanopentyl)thio] - 1 - deoxy - - D - mannopyranoside, 1 - [(6 cyanohexyl)thio] - 1 - deoxy - a - D - mannopyranoside, 1 - [(6 - cyanohexyl)thio] - 1 - deoxy - ss - D - glucopyranoside or 1 - [(6 cyanohexyl)thioi - 1 - deoxy - ss - D - galactopyranoside.

The 1 - [(w - cyanoalkyl)thio] - 1 - deoxy - glycopyranoside is then reacted with hydrogen in the presence of a Raney nickel catalyst, e.g. by vigorously agitating a solution of it in ethanolic ammonia in contact with hydrogen at a pressure of about 40 pounds per square inch in the presence of Raney-nickel catalyst and at a temperature of about 25 C. Under these conditions, the hydrogenation reaction is ordinarily complete in about eight hours. The hydrogenation mixture is filtered through diatomaceous silica, the filtered solution is evaporated in vacuo, and the residual material subjected to chromatography to give the corresponding 1 - [(a) - aminoalkyl)thio] - 1 - deoxy - glycopyranoside, such as 1 - [(6 - aminohexyl)thiol - 1 - deoxy - - D - mannopyranoside, 1 - [(7 - aniinoheptyl)thiol - 1 - deoxy - a - D - mannopyranoside, I - [(7 - aminoheptyl)thio] - 1 - deoxy- ss- D- glucopyranoside or 1 - [(7 aminoheptyl)thiol - 1 - deoxy - ss - D - galactopyranoside.

The 1 - [(a) - aminoalkanoyl)amino] - 1 - deoxy - glycopyranosides are ordinarily prepared by reacting, e.g. by bringing together in solution an organic solvent such as methylene chloride, a hexose pentaacetate, such as D-mannose pentaacetate, D - glucose pentaacetate or D - galactose pentaacetate, stannic chloride and trimethylsilylazide. By vigorously agitating the resulting mixture at a temperature of about 25"C, the reaction is ordinarily complete in about six hours.

The methylene chloride reaction solution is washed with water, aqueous sodium bicarbonate solution, and dried, and then evaporated in vacuo to a syrup which ordinarily crystallizes upon standing to give the corresponding tetra - 0 - acetyl glycopyranosyl azide, such as 2,3,4,6- tetra - 0 - acetyl - a - D - mannopyranosyl azide, 2,3,4,6 - tetra - O - acetyl - A - D - glucopyranosyl azide, 2,3,4,6 - tetra - 0 - acetyl - - D - galactopyranosyl azide, and the like.

This tetra - 0 - acetyl - glycopyranosyl azide is then reacted with hydrogen in the presence of Raney nickel. If the azide dissolved in an organic solvent such as ethyl acetate, Raney nickel catalyst is added, and the mixture is vigorously agitated with hydrogen at about 25"C, the hydrogenation reaction with accompanying inversion is substantially complete in about six hours. The hydrogenation mixture may then be filtered through diatomaceous silica, and the filtered solution evaporated to a syrup which ordinarily crystallizes upon standing in the cold to give the corresponding tetra - 0 - acetyl - glycopyranosylamine such as, 2,3,4,6 tetra - 0 - acetyl - - D - mannopyranosylamine, 2,3,4,6 - tetra - O - acetyl - p- D- glucopyranosylamine or 2,3,4,6 - tetra - 0 - acetyl - - D- galactopyranosylamine.

This tetra - 0 - acetyl - glycopyranosylamine is reacted with a w- - benzyloxycarbonylamino - alkanoylating agent such as the halide, the anhydride, or the acid in the presence of a condensing agent such as dicyclohexyl carbodiimide. Suitable halides include 5 - benzyloxycarbonylaminopentanoyl chloride, 6- benzyloxycarbonylamino - hexanoyl chloride and 7benzyloxycarbonylamino - heptanoyl chloride. The reaction is conveniently carried out by bringing the reactants together in solution in an organic solvent such as methylene chloride in the presence of 4- dimethylaminopyridine, and vigorously agitating the mixture at a temperature of about 25"C, under which conditions the reaction is ordinarily complete in about one hour. The methylene chloride reaction mixture, which may be diluted with additional methylene chloride, is washed with aqueous hydrochloric acid solution, with aqueous sodium bicarbonate solution, and with water. The methylene chloride solution is then evaporated to small volume, and the resulting solution is subjected to chromatography over silica gel, preferably using a 1:1 mixture of ethylacetate:chloroform as eluant, to give the corresponding 1 - [(a) - benzyloxycarbonylamino - alkanoyl)aminol - tetra - 0 - acetyl - 1 - deoxy - glycopyranoside, such as 1 - [(5 - benzyloxycarbonylamino - pentanoyl)amino] 2,3,4,6 - tetra - O - aeetyl - 1 - deoxy - - D - mannopyranoside, 1 - ((6 - benzyloxycarbonylamino - hexanoyl)amino] - 2,3,4,6 - tetra- O - aeetyl - 1 - deoxy - p- D - mannopyranoside, 1 - [(7 - benzyloxycarbonylamino heptanoyl)amino] - 2,3,4,6 - tetra - 0 - acetyl - 1 - deoxy - - D - mannopyranoside, 1 - [(7 - benzyloxycarbonylamino - heptanoyl)amino] 2,3,4,6 - tetra - 0 - acetyl - 1 - deoxy - A - D - glucopyranoside or 1 - [(7 benzyloxycarbonylamino - heptanoyl)amino] - 2.3,4,6 - tetra - O - acetyl - 1 - deoxy - ss - D - galactopyranoside.

A solution of 1 - [(w - benzyloxycarbonylamino - alkanoyl)amino] - tetra 0 - acetyl - 1 - deoxy - glycopyranoside in a C16 alkanol is then reacted with an alkali metal alkoxide. For example, a solution in dry methanol is reacted at a temperature of 25"C with a catalytic amount of sodium methoxide, under which conditions the deacetylation reaction is ordinarily complete in about two hours.

The reaction solution is neutralized by stirring with an acidic resin, the resin is removed by filtration, and the filtrate is evaporated to give the corresponding 1 [(a) - benzyloxycarbonylamino - alkanoyl)amino] - 1 - deoxy - glycopyranoside, such as 1 - [(5 - benzyloxycarbonylamino - pentanoyl)aminoi - 1 - deoxy - fi D - mannopyranoside, 1 - [(6 - benzyloxycarbonylamino - hexanoyl)amino] - 1 deoxy - ,6- D- mannopyranoside, I - [(7 - benzyloxycarbonylamino heptanoyl)amino] - 1 - deoxy - - D- mannopyranoside, 1 - [(7 - benzyloxycarbonylamino - heptanoyl)amino] - 1 - deoxy - - D glucopyranoside or 1 - [(7 - benzyloxycarbonylamino - heptanoyl)amino] - 1 deoxy - p - D - galactopyranoside.

This compound is then reacted with hydrogen in the presence of a palladium on-carbon catalyst. For example, a mixture of a solution of 1 - [(o - benzyloxycarbonylamino - alkanoyl)amino]- 1 - deoxy - glycopyranoside in aqueous methanol and a catalytic amount of palladium-on-carbon catalyst is vigorously agitated in contact with a hydrogen atmosphere at atmospheric pressure and at a temperature of about 2M C, under which conditions the hydrogenation reaction is ordinarily complete in about one hour. The hydrogenation mixture is filtered through diatomaceous silica, and the filtered solution is evaporated in vacuo to give the corresponding 1 - [( - - aminoalkanoyl)amino] - 1 - deoxy - glycopyranoside such as 1 - [(5 amino - pentanoyl)aminoi - 1 - deoxy - ,B - D - mannopyranoside, 1 - [(6 - amino hexanoyl)amin6j - 1 - deoxy - - - mannopyranoside, I - [(7- amino- heptanoyl)amino] - 1 - deoxy - - D - mannopyranoside, 1 - [(7 - amino - heptanoyl)amino] - 1 - deoxy - ,B - D - glucopyranoside or 1 - [(7 - amino heptanoyl)aminoj - 1 - deoxy - p - D - galactopyranoside.

The following Examples illustrate methods of carrying out the present invention, but it is to be understood that these Examples are given for purposes of illustration and not of limitation.

EXAMPLE 1 A mixture of about 35 grams 2,3,4,6 - tetra - 0 - acetyl - ct -. D - mannopyranosyl bromide, 6.7 grams thiourea and 4 to give about 1.4 grams of 1 - [(6 - trifluoroacetylamino - hexyl)thio] - 2,3,4,6 tetra - 0 - acetyl - 1 - deoxy - p - D - mannopyranoside; m.p. 121--1220C, [a]5-47.60 (c 1, chloroform).

A mixture of about 0.9 gram 1 - [(6 - trifluoroacetylamino - hexyl)thio] 2,3,4,6 - tetra - 0 - acetyl - 1 - deoxy - p - D - mannopyranoside, 46 ml of 50 /n aqueous ethanol, 20 milliequivalents of a strongly basic anion-exchange resin on the hydroxyl cycle comprising quaternary ammonium groups attached to a styrenedivinylbenzene copolymer, is stirred vigorously at a temperature of about 25"C for a period of approximately 15 hours. The reaction mixture is filtered, the insoluble resin is washed thoroughly with methanol, and the combined filtrate and washings are evaporated to dryness. The residual solid material is recrystallized from ethanol to give approximately 422 mg of substantially pure 1 - [(6 - aminohexyl)thio] - 1 deoxy - - D - mannopyranoside; m.p. 161.8--163.80C, [a]2583.l0 (c 1, methanol).

EXAMPLE 3 To a mixture of about 10.5 grams of 2,3,4,6 - tetra - 0 - acetyl - 1 - deoxy a - D - mannopyranosylisot iouronium bromide monohydrate, 3.3 grams potassium carbonate, 4.6 grams potassium metabisulfite, and about 20 ml water, is added, with stirring, a solution of about 20.8 millimoles of 6 - iodo - 1 - hexanol in 20 ml acetone. The mixture is stirred at a temperature of about 25"C for a period of approximately 30 minutes, and the acetone is evaporated from the reaction mixture. The residual aqueous mixture is extracted with dichloromethane, and the dichloromethane extract is washed with water, dried over anhydrous sodium sulfate and evaporated to dryness. The residual material is dissolved in chloroform.

and the solution is subjected to chromatography on a silica gel column, using a 10:1 mixture of chloroform-ethyl acetate as e4uant. The chromatographed product is crystallized from ethanol to give about 6.8 grams of substantially pure 1 - [(6 hydroxyhexyl)thio] - 2,3,4,6 - tetra - 0 - acetyl - 1 - deoxy - a - D - mannopyranoside, m.p. 91-920C, [a]D5+93.6 (c 1, chloroform).

To a solution of about 3.0 grams of 1 - [(6 - hydroxyhexyl)thio] - 2,3,4,6 tetra - 0 - acetyl - 1 - deoxy - a - D - mannopyranoside in 6 ml dry pyridine is added a solution of about 1.4 grams of p - toluenesulfonyl chloride in 3.0 ml of chloroform. The mixture is stirred at a temperature of about 0 C for a period of approximately 4 hours. The reaction mixture is poured into ice-water, and the aqueous mixture is extracted with three 30 ml portions of dichloromethane. The combined dichloromethane extracts are washed with aqueous sodium bicarbonate solution and with cold water and dried over anhydrous sodium sulfate, and the dried dichloromethane solution is evaporated in vacuo, followed by vacuum codistillation with toluene, thereby substantially completely evaporating the pyridine. The residual material is dissolved in dichloromethane, and the solution is subjected to chromatography on a silica gel column, using a 2:1 (v/v) mixture of ether:petroleum ether as eluant. The chromatographed product is recrystallized from ethanol to give approximately 1.8 grams of 1 - [(6 - p - toluenesulfonyloxy hexyl)thio] - 2,3,4,6 - tetra - O - acetyl - I - deoxy - a - D - mannopyranoside, m.p. 73.8-74.40C, [a]25+l04 (c 1, chloroform).

A mixture of about 0.82 grams of 1 - [(6 - p- toluenesulfonyloxy hexyl)thio] - 2,3,4,6 - tetra - O - acetyl - I - deoxy - a - D - mannopyranoside, 0.23 grams sodium cyanide, and 10 ml dry dimethylformamide, is heated, with stirring, at a temperature of about 45"C and under substantially anhydrous conditions, for a period of approximately four hours. The reaction mixture is poured into 50 ml of ice-water, and the aqueous mixture is extracted with three 25 ml portions of dichloromethane. The combined dichloromethane extracts are washed with ice-water, dried over anhydrous sodium sulfate, and evaporated to dryness in vacuo. The residual material is reacted with excess acetic anhydride and pyridine at a temperature of 25"C for a period of about 15 hours. The reaction mixture is subjected to distillation in vacuo followed by vacuum codistillation with toluene. The resulting syrup is dissolved in chloroform and the solution subjected to chromatography on silica gel, using 9:1 (v/v) mixtures of chloroform:ethyl acetate as eluant, to give about 0.5 gram 1 - [(6 - cyanohexyl)thio] - 2,3,4,6 tetra - 0 - acetyl - 1 - deoxy - a - D - mannopyranoside, m.p. 88-89.20C, [a]D5+91.7 (c 1, chloroform).

A mixture of about 1 gram of 1 - [(6 - cyanohexyl)thio] - 2,3,4,6 - tetra - 0 acetyl - 1 - deoxy - a - D - mannopyranoside, 5 ml dry methanol, and a catalytic amount of sodium methoxide, is stirred at a temperature of about 250C for a period of approximately 15 hours. About 0.1 gram of a strongly acidic cation-exchange sulfonated-styrene-divinylbenzene-copolymer resin on the hydrogen cycle is added to the reaction solution; the mixture is stirred, thereby adsorbing the sodium cation on the resin, and the resulting mixture is filtered through diatomaceous silica. The filtered reaction solution is evaporated in vacuo to a syrup which crystallizes from ethyl acetate-ethyl ether. The crystalline material is recovered by filtration and dried to give a substantially quantitative yield of 1 - [(6 - cyanohexyl)thio - 1 deoxy - a - D - mannopyranoside, m.p. 82-830C, []D5+181 (c 1, methanol).

A mixture of about 200 mg of 1 - [(6 - cyanohexyl)thio] - 1 - deoxy - a - D mannopyranoside, 200 mg of Raney nickel catalyst, and 10 ml of ethanolic ammonia containing 3 grams of ammonia, is vigorously agitated with hydrogen at an initial pressure of approximately 40 pounds/in2 at a temperature of about 25"C for a period of approximately eight hours. The reaction mixture is filtered through diatomaceous silica, and the filtered solution is evaporated to dryness. The residual material is dissolved in methanol-chloroform (1:1), and the solution is subjected to chromatography on a silica gel column, using a 3:3:1 mixture of chloroform:methanol:ammonia as eluant, to give about 120 mg of 1 - [(7 aminoheptyl)thiol - 1 - deoxy - a - D - mannopyranoside.

EXAMPLE 4 A solution of 10 grams of 2,3,4,6 - tetra - 0 - acetyl - a - D mannopyranosyl bromide in 50 ml of dry benzene is added to a solution of 5.01 grams of 6 - (benzyloxycarbonylamino) - 1 - hexanol in 250 ml of nitromethane containing 5.3 grams mercuric cyanide and 5 grams calcium sulfate. The mixture is stirred at a temperature of about 25"C for a period of approximately 15 hours, the reaction mixture is filtered, and the filtered solution is evaporated to dryness in vacuo. The residual material is dissolved in chloroform, and the chloroform solution is washed successively with water, with aqueous sodium bicarbonate solution, and again with water, then dried, and the dry chloroform solution is evaporated to a smaller volume. The material, which precipitates, about 2 grams of unreacted 6 (benzyloxycarbonylamino) - 1 - hexanol, is separated by filtration, and the filtered solution is subjected to chromatography on a silica gel column, using 15% ethyl acetate in chloroform as eluant, to give, as a syrup, about 3.6 grams of 1 - (6 benzyloxycarbonylamino - hexyl) - 2,3,4,6 - tetra - 0 - acetyl - a - D - mannopyranoside.

A solution of about 3 grams of 1 - (6 - benzyloxycarbonylamino - hexyl) 2,3,4,6 - tetra - 0 - acetyl - xx - D - mannopyranoside, and 200 mg of sodium methoxide in 20 ml of dry methanol is maintained at a temperature of about 25"C for a period of approximately two hours. The solution is then neutralized by stirring with an acidic resin, filtered, and the filtrate is evaporated in vacuo to give, as a crystalline product, about 2 grams of 1 - (6 - benzyloxycarbonylamino - hexyl) cg - D - mannopyranoside, m.p. 800 C, [a]25+460 (c 1, methanol).

A mixture of about 700 mg of 1 - (6 - benzyloxycarbonylamino - hexyl) - a D - mannopyranoside, 20 ml aqueous methanol, and 200 mg of a 10 /" palladiumon-carbon catalyst is vigorously agitated with hydrogen at atmospheric pressure and at a temperature of about 25"C, for a period of approximately one hour. The reaction mixture is filtered through diatomaceous silica, and the filtered solution is subjected to chromatography on a silica gel column using a 60:40:10 (v/v) mixture of chloroform:methanol:50 /n aqueous ammonium hydroxide as eluant to give about 450 mg of 1 - (6 - aminohexyl) - a - D - mannopyranoside, Rf 0.2.

EXAMPLE 5 About 2 ml stannic chloride is added to a solution of 8 grams of D - mannose pentaacetate and 2.6 ml trimethylsilyl azide in 180 ml methylene chloride, and the resulting mixture is stirred at a temperature of about 25"C for a period of approximately six hours. The reaction solution is diluted with an additional 100 ml of methylene chloride, and the resulting methylene chloride solution is washed successively with water, with aqueous sodium bicarbonate solution, and again with water, and dried over anhydrous sodium sulfate. The dry methylene chloride solution is evaporated in vacuo to a syrup which crystallized upon standing to give approximately 7.6 grams of 2,3,4,6 - tetra - 0 - acetyl - a - D - mannopyranosyl azide, m.p. 52--530C (after recrystallization from 2 - propanol), [al2+ 1160 (c 1.02, chloroform).

To a mixture of about 3.0 grams of 2,3,4,6 - tetra - 0 - acetyl - a - D mannopyranosyl azide, 0.5 grams Raney nickel catalyst, and 40 ml ethyl acetate, is vigorously agitated with hydrogen at atmospheric pressure, at a temperature of about 25"C for a period of about 6.5 hours. The reaction mixture is filtered through diatomaceous silica, and the filtered solution is evaporated in vacuo to a syrup which crystallizes upon standing at a temperature of abour 5"C. The crystalline product is recrystallized from 2 - propanol to give about 1.7 grams of 2,3,4,6 tetra - O - acetyl - ,B - D - mannopyranosylamine, m.p. 145--1470C, [cz] 259.8 (c 1.02, methanol).

A mixture of about 0.87 grams of 2,3,4,6 - tetra - 0 - acetyl - - D - mannopyranosylamine, 0.75 gram 7 - benzyloxycarbonylamino - heptanoyl chloride, 62 mg 4 - dimethylaminopyridine, and 20 ml methylene chloride, is stirred at a temperature of about 25"C for a period of approximately one hour. The reaction mixture is diluted with an additional 20 ml methylene chloride, and the resulting mixture washed successively with 1N aqueous hydrochloric acid solution, with aqueous sodium bicarbonate solution, and then with water. The methylene chloride solution is evaporated to small volume, and then subjected to chromatography over silica gel using a 1:1 (v/v) mixture of ethyl acetate:chloroform as eluant to give about 0.9 gram of 1 - [(7 - benzyloxycarbonylamino heptanoyl)amino] - 2,3,4,6 - tetra - 0 - acetyl - 1 - deoxy - p- D- mannopyranoside, []D7.6+0.6 (c 1.58, chloroform).

A solution of about 50 mg of sodium methoxide, 1.13 grams of 1 - [(7 benzyloxycarbonylamino - heptanoyl)aminoi - 2,3,4,6 - tetra - O - acetyl - 1 deoxy - ,B - D - mannopyranoside, and 25 ml dry methanol, is maintained at a temperature of about 25"C for a period of approximately two hours. The reaction solution is neutralized by stirring with an acidic resin, filtered, and the filtrate evaporated in vacuo to give a crystalline material which, upon recrystallization from methanol, gives about 0.76 grams of 1 - [(7 - benzyloxycarbonylamino heptanoyl)amino] - 1 - deoxy - - D - mannopyranoside; m.p. 169--172"C, α]D -7.4#0.3 (c 1.0, methanol).

A mixture of about 200 mg of 1 - [(7- benzyloxycarbonylamino heptanoyl)amino] - 1 - deoxy - - D - mannopyranoside, 10 ml of aqueous methanol, and 80 mg of 10% palladium-on-carbon catalyst is vigorously agitated with hydrogen at atmospheric pressure and at a temperature of about 25"C for a period of approximately one hour. The reaction mixture is filtered through diatomaceous silica, and the filtered solution is evaporated in vacuo to a crystalline material, which is triturated with ethanol, recovered by filtration and dried to give approximately 125 mg of 1 - [(7 - aminoheptanoyl)amino] - 1 - deoxy - ,B - D mannopyranoside, m.p. 1620C (dec.), [α]D19.4 #0.5 (c 1.59, water).

WHAT WE CLAIM IS: 1. The process for preparing 1 - [(cl) - aminoalkyl) - glycopyranosides, which comprises reacting a tetra - 0 - acetyl - glycopyranosyl bromide with an a) benzyloxycarbonylamino) - 1 - alkanol to form the corresponding 1 - [(co benzyloxycarbonylamino - alkyl) - tetra - O - acetyl - glycopyranoside, reacting the latter compound with an alkali metal alkoxide in solution in a C16 alkanol to produce the corresponding 1 - ( - benzyloxycarbonylamino - alkyl) - glycopyranoside; and reacting this 1 - (a) - benzyloxycarbonylamino - alkyl) glycopyranoside with hydrogen, thereby forming the corresponding 1 -(w - aminoalkyl) - glycopyranoside.

2. A process as claimed in Claim 1, which comprises reacting 2,3,4,6 - tetra 0 - acetyl - a - D - mannopyranosyl bromide with 6 (benzyloxycarbonylamino) - 1 - hexanol to form 1 - (6 benzyloxycarbonylamino - hexyl) - 2,3,4,6 - tetra - 0 - acetyl - a - D - mannopyranoside, reacting the latter compound with sodium methoxide in methanol solution to produce 1 - (6 - benzyloxycarbonylamino - hexyl) - a - D mannopyranoside: and reacting this 1 - (6 - benzyloxycarbonylamino - hexyl) 2,3,4,6 - tetra - 0 - acetyl - a - D - mannopyranoside with hydrogen in the presence of palladium-on-carbon catalyst, thereby forming I - (6 - aminohexyl) - D - mannopyranoside.

3. The process which comprises (a) reacting a 1 - thio - hexose alkali metal salt with I - iodo - - - trifluoroacetylamino - alkane followed by acetylation; or (b) reacting tetra - 0 - acetyl - glycopyranosyl bromide with thiourea in solution in a substantially anhydrous polar organic solvent to form the corresponding tetra - 0 - acetyl - 1 - deoxy - glycopyranosvl - isothiouronium

**WARNING** end of DESC field may overlap start of CLMS **.

Claims (17)

**WARNING** start of CLMS field may overlap end of DESC **. vigorously agitated with hydrogen at atmospheric pressure, at a temperature of about 25"C for a period of about 6.5 hours. The reaction mixture is filtered through diatomaceous silica, and the filtered solution is evaporated in vacuo to a syrup which crystallizes upon standing at a temperature of abour 5"C. The crystalline product is recrystallized from 2 - propanol to give about 1.7 grams of 2,3,4,6 tetra - O - acetyl - ,B - D - mannopyranosylamine, m.p. 145--1470C, [cz] 259.8 (c 1.02, methanol). A mixture of about 0.87 grams of 2,3,4,6 - tetra - 0 - acetyl - - D - mannopyranosylamine, 0.75 gram 7 - benzyloxycarbonylamino - heptanoyl chloride, 62 mg 4 - dimethylaminopyridine, and 20 ml methylene chloride, is stirred at a temperature of about 25"C for a period of approximately one hour. The reaction mixture is diluted with an additional 20 ml methylene chloride, and the resulting mixture washed successively with 1N aqueous hydrochloric acid solution, with aqueous sodium bicarbonate solution, and then with water. The methylene chloride solution is evaporated to small volume, and then subjected to chromatography over silica gel using a 1:1 (v/v) mixture of ethyl acetate:chloroform as eluant to give about 0.9 gram of 1 - [(7 - benzyloxycarbonylamino heptanoyl)amino] - 2,3,4,6 - tetra - 0 - acetyl - 1 - deoxy - p- D- mannopyranoside, []D7.6+0.6 (c 1.58, chloroform). A solution of about 50 mg of sodium methoxide, 1.13 grams of 1 - [(7 benzyloxycarbonylamino - heptanoyl)aminoi - 2,3,4,6 - tetra - O - acetyl - 1 deoxy - ,B - D - mannopyranoside, and 25 ml dry methanol, is maintained at a temperature of about 25"C for a period of approximately two hours. The reaction solution is neutralized by stirring with an acidic resin, filtered, and the filtrate evaporated in vacuo to give a crystalline material which, upon recrystallization from methanol, gives about 0.76 grams of 1 - [(7 - benzyloxycarbonylamino heptanoyl)amino] - 1 - deoxy - - D - mannopyranoside; m.p. 169--172"C, α]D -7.4#0.3 (c 1.0, methanol). A mixture of about 200 mg of 1 - [(7- benzyloxycarbonylamino heptanoyl)amino] - 1 - deoxy - ss - D - mannopyranoside, 10 ml of aqueous methanol, and 80 mg of 10% palladium-on-carbon catalyst is vigorously agitated with hydrogen at atmospheric pressure and at a temperature of about 25"C for a period of approximately one hour. The reaction mixture is filtered through diatomaceous silica, and the filtered solution is evaporated in vacuo to a crystalline material, which is triturated with ethanol, recovered by filtration and dried to give approximately 125 mg of 1 - [(7 - aminoheptanoyl)amino] - 1 - deoxy - ,B - D mannopyranoside, m.p. 1620C (dec.), [α]D19.4 #0.5 (c 1.59, water). WHAT WE CLAIM IS:

1. The process for preparing 1 - [(cl) - aminoalkyl) - glycopyranosides, which comprises reacting a tetra - 0 - acetyl - glycopyranosyl bromide with an a) benzyloxycarbonylamino) - 1 - alkanol to form the corresponding 1 - [(co benzyloxycarbonylamino - alkyl) - tetra - O - acetyl - glycopyranoside, reacting the latter compound with an alkali metal alkoxide in solution in a C16 alkanol to produce the corresponding 1 - ( - benzyloxycarbonylamino - alkyl) - glycopyranoside; and reacting this 1 - (a) - benzyloxycarbonylamino - alkyl) glycopyranoside with hydrogen, thereby forming the corresponding 1 -(w - aminoalkyl) - glycopyranoside.

2. A process as claimed in Claim 1, which comprises reacting 2,3,4,6 - tetra 0 - acetyl - a - D - mannopyranosyl bromide with 6 (benzyloxycarbonylamino) - 1 - hexanol to form 1 - (6 benzyloxycarbonylamino - hexyl) - 2,3,4,6 - tetra - 0 - acetyl - a - D - mannopyranoside, reacting the latter compound with sodium methoxide in methanol solution to produce 1 - (6 - benzyloxycarbonylamino - hexyl) - a - D mannopyranoside: and reacting this 1 - (6 - benzyloxycarbonylamino - hexyl) 2,3,4,6 - tetra - 0 - acetyl - a - D - mannopyranoside with hydrogen in the presence of palladium-on-carbon catalyst, thereby forming I - (6 - aminohexyl) - D - mannopyranoside.

3. The process which comprises (a) reacting a 1 - thio - hexose alkali metal salt with I - iodo - - - trifluoroacetylamino - alkane followed by acetylation; or (b) reacting tetra - 0 - acetyl - glycopyranosyl bromide with thiourea in solution in a substantially anhydrous polar organic solvent to form the corresponding tetra - 0 - acetyl - 1 - deoxy - glycopyranosvl - isothiouronium

bromide, and reacting the latter compound with a metabisulfite followed by a I iodo - a) - trifluoroacetylamino - alkane; thereby forming the corresponding 1 - [(a) - trifluoroacetylamino - alkyl)thio] tetra - 0 - acetyl - 1 - deoxy - glycopyranoside; and reacting the latter compound with a strongly basic anion exchange resin on the hydroxyl cycle, thereby hydrolyzing the acetyl and trifluoroacetyl groupings to produce the corresponding I - [( - aminoalkyl)thioi - 1 - deoxy - glycopyranoside.

4. A process as claimed in Claim 3, which comprises reacting 1 - thio - ss - D mannose sodium salt with 1 - iodo - 6 - trifluoroacetylamino - hexane and reacting the resulting product with acetic anhydride to form 1 - [(6 trifluoroacetylamino - hexyl)thio) - 2,3,4,6 - tetra - O - acetyl - 1 - deoxy - p - D - mannopyranoside, and reacting the latter compound with a strongly basic anion exchange resin on the hydroxyl cycle, thereby forming 1 - [(6 aminohexyl)thio] - 1 - deoxy - ,B - D - mannopyranoside.

5. A process as claimed in Claim 3, which comprises reacting 2,3,4,6 - tetra O - acetyl - a - D - mannopyranosyl bromide with thiourea in anhydrous acetone solution to form 2,3,4,6 - tetra - 0 - acetyl - 1 - deoxy - a - D - mannopyranosyl isothiouronium bromide, reacting the latter compound with potassium metabisulfite followed by 1 - iodo - 6 - trifluoroacetylamino - hexane thereby forming 1 - [(6 - trifluoroacetylamino - liexyi)thio] - 2,3,4,6 - tetra - 0 - acetyl trifluoroacetylamino - hexyl)thioi - 2,3,4,6 - tetra - O - acetyl - 1 - deoxy a - D - mannopyranoside with a strongly basic anidn exchange resin to form 1 - [(6 - amino - hexyl)thio] - 1 - deoxy - a - D - mannopyranoside.

6. The process which comprises reacting a tetra - 0 - acetyl - 1 - deoxy glycopyranosyl - isothiouronium bromide with an a) - iodo - 1 - alkanol to form I - [( - hydroxyalkyl)thiol - tetra - O - acetyl - I - deoxy - glycopyranoside; reacting the latter compound with p - toluenesulfonylchloride in the presence of a base thereby forming the corresponding p - toluenesulfonate; reacting the said p toluenesulfonate with sodium cyanide in dimethylformamide solution to form the corresponding I - [( - cyanohexyl)thio] - tetra - O - acetyl - I - deoxy glycopyranoside; reacting this 1 - [( - cyanohexyl)thio] - tetra - 0 - acetyl - 1 deoxy - glycopyranoside with a catalytic amount of alkali metal alkoxide in solution in a C16 alkanol thereby removing the acetyl groupings to form the 1 [(ev- cyanohexyl)thio] - 1 - deoxy - glycopyranoside, and reacting this deacetylated product with hydrogen in the presence of Raney nickel catalyst thereby forming the corresponding 1 - [(a) - aminoalkyl)thio] - 1 - deoxy glycopyranoside.

7. A process as claimed in Claim 6, welch comprises reacting 2,3,4,6 - tetra 0 - acetyl - 1 - deoxy - a - D - mannopyranosyl - isothiouronium bromide with 6 - iodo - 1 - hexanol to form 1 - [(6 - hydroxyhexyl)thio] - 2,3,4,6 - tetra - 0 acetyl - 1 - deoxy - a - D - mannopyranoside; reacting the latter compound with p- toluenesulfonylchloride in pyridine to form the corresponding ptoluenesulfonate reacting the said p - toluenesulfenate with sodium cyanide in dimethylformamide solution to form 1 - [(6 - cyanohexyl)thio] - 2,3,4,6 - tetra O - acetyl - 1 - deoxy - a - D - mannopyranoside; reacting the 1 - [(6 - cyanohexyl)thio] - 2,3,4,6 - tetra - 0 - acetyl - 1 - deoxy - a- Dmannopyranoside with a catalytic amount of sodium methoxide in dry methanol to form 1 - [(6 - cyanohexyl)thio]- 1 - deoxy - a - D - mannopyranoside; and reacting this 1 - [(6 - cyanohexyl)thio] - 1 - deoxy - a - D - mannopyranoside in ethanolic ammonia solution with hydrogen in the presence of Raney nickel catalyst to form I - [(7 - aminoheptyl)thio] - 1 - deoxy - a - D - mannopyranoside.

8. A process for preparing a 1 - [(o - aminoalkanoyl)] - 1 - deoxy glycopyranosides which comprises reacting a hexose pentaacetate with stannic chloride and trimethylsilylazide to form the corresponding tetra - 0 - acetyl glycopyranosyl azide; reacting this azide with hydrogen in the presence of Raneynickel catalyst to form the corresponding tetra - 0 - acetyl glycopyranosylamine; reacting this tetra - 0 - acetyl - glycopyranosylamine with an a) - benzyloxycarbonylamino - alkanoylating agent thereby forming the corresponding 1 - [(a) - benzyloxycarbonylaminoalkanoyl)amino] - tetra - 0 - acetyl - 1 - deoxy - glycopyranoside; reacting the latter compound with an alkali metal alkoxide in solution in a C16 alkanol to form the corresponding I - [(# benzyloxycarbonylaminoalkanoyl)amino] - 1 - deoxy - glycopyranoside; and reacting this I - [(cl) - benzyloxycarbonylamino - alkanoyl)amino] - 1 - deoxy glycopyranoside with hydrogen in the presence of palladium-on-carbon catalyst thereby forming the corresponding 1 - [( - aminoalkanoyl)amino] - 1 - deoxy glycopyranoside.

9. A process as claimed in Claim 8, which comprises reacting D - mannose pentaacetate with stannic chloride and trimethylsilylazide in methylene chloride solution, thereby forming 2,3,4,6 - tetra - 0 - acetyl - a - D - mannopyranosyl azide; reacting this 2,3,4,6 - tetra - 0 - acetyl - a - D - mannopyranosyl azide with hydrogen in the presence of Raney nickel catalyst to form 2,3,4,6 - tetra - 0 acetyl - p - D - mannopyranosyl amine; reacting the latter compound with 7 benzyloxycarbonylamino - heptanoyl chloride in the presence of 4dimethylamino - pyridine to produce 1 - [(7- benzyloxycarbonylamino heptanoyl)amino] - 2,3,4,6 - tetra- O- acetyl- 1 - deoxy - p- D - mannopyranoside; reacting the said 1 - [(7- benzyloxycarbonylamino heptanoyl)amino] - 2,3,4,6 - tetra - 0 - acetyl - 1 - deoxy - p- D- mannopyranoside with sodium methoxide in dry methanol to form 1 - [(7 benzyloxycarbonylamino - heptanoyl)amino] - 1 - deoxy - A- Dmannopyranoside; and reacting the 1 - [(7- benzyloxycarbonylamino heptanoyl)amino] - 1 - deoxy - fi - D - mannopyranoside with hydrogen in the presence of palladium-on-carbon catalyst thereby forming 1 - [(7 aminoheptanoyl)amino] - 1 - deoxy - A - D - mannopyranoside.

10. 1 - ( - aminoalkyl)glycopyranosides, 1 - [( - aminoalkyl)thio] - 1 - deoxy - glycopyranosides and 1 - [(a) - aminoalkanoyl)amino] - I - deoxy glycopyranosides.

11. 1 - (6 - aminohexyl) - a - D - mannopyranoside.

12. 1 - [(6 - aminohexyl)thio] - 1 - deoxy - a - D - mannopyranoside.

13. 1 - [(6 - aminohexyl)thio] - 1 - deoxy - 5 - D - mannopyranoside.

14. 1 - [(7 - aminoheptyl)thio] - 1 - deoxy - a - D - mannopyranoside.

15. 1 - [(7 - aminoheptanoyl)amino] - 1 - deoxy - 3 - D - mannopyranoside.

16. A process for producing a compound as claimed in Claim 10 substantially as hereinbefore described in any one of the Examples.

17. A compound as claimed in Claim 10 when prepared by a process as claimed in any one of Claims 1 to 9 and 16.