Patent GB-909278-A (GB)
Title: New sugar derivatives, a process for their manufacture and pharmaceutical preparations containing them
IPC: C07H15/18
Filed: 1959-12-31
Abstract: The invention comprises D-glucofuranosides of the general formula <FORM:0909278/IV (b)/1> and their 2-O-substituted derivatives in which the 2-substituent is an acyl radical of a carboxylic or sulphonic acid or a substituted or unsubstituted non-aromatic or hetero cyclyl aliphatic hydrocarbon radical, wherein R1 contains at least 2 carbon atoms and represents the organic radical of an alcohol and R3, R5 and R6 each represent the organic radical of an alcohol or an acyl radical of an aromatic or heterocyclic carboxylic acid, and the salts of such of these compounds as contain a basic or acidic group.  The Rs and 2-O-substituent may represent alkyl, alkenyl, such as allyl, and alkinyl, such as propinyl, groups which may be substituted by free or substituted amino, hydroxy and mercapto groups including dimethylamino, pyrrolidino, piperidino, morpholino, piperazino, alkoxy and alkyl mercapto groups, or by chlorine, bromine or fluorine, or carbalkoxy, carbamyl or nitrile groups; they may also represent alicyclic hydrocarbon radicals e.g., cyclo pentyl, cyclo hexenyl or cyclopentylmethyl or araliphatic hydrocarbon radicals such as benzyl and phenethyl radicals; aryl radicals may bear substituents e.g. alkoxy groups (including methylene dioxy), halogen or alkyl groups including trifluoro methyl; they may also represent hetero cyclyl aliphatic radicals such as the residues of thienyl, furyl and pyridyl carbinols.  The above mentioned acyl radicals may be derived, as appropriate, from alkane- and alkene-carboxylic acids, such as formic to butyric acids, alicyclic carboxylic acids e.g. cyclopentyl carboxylic acid, alicyclicaliphatic carboxylic acids, aromatic and araliphatic carboxylic acids such as benzoic and phenyl acetic acids which may be nuclearly substituted as by alkoxy, alkyl, halogen or trifluoromethyl, heterocyclic carboxylic acids such as pyridine, thiophene, furane, pyrrole, pyrazole, pyridazine and pyrimidine carboxylic acids, and (in the 2-position) from benzene sulphonic acids.  The furanosides unsubstituted in the 2-position are prepared by etherifying the corresponding D-glucofuranoses whose hydroxyls in the 1- and 2-positions are substituted by a methylidene group (e.g. isopropylidene) with an alcohol R1OH in the presence of a Lewis acid such as hydrochloric, sulphuric, glacial acetic or toluene sulphonic acid or an acid salt.  The resulting 2-OH compounds may be 2-substituted by reaction with a reactive ester of an alcohol, for example a hydrochloric, sulphuric or toluene sulphonic acid ester, or with a carboxylic acid halide or anhydride or sulphonic acid halide, preferably in the presence of a tertiary base, sodium acetate or other acid-binding agent.  The new compounds containing basic (amino) or acidic (e.g. carboxylic) groups may be converted into salts and alkali metal, alkaline earth metal and ammonium bases and numerous inorganic and organic acids are specified.  The compounds and their salts may be used as medicaments (see Group VI).  They can also be converted into O-unsubstituted D-glucofuranoxides by eliminating the groups R3, R5 and R6 and the 2-O-substituent by hydrolysis or hydrogenolysis.  Examples describe the preparation of (1) ethyl-3 : 5 : 6-tribenzyl-D-glucofuranoside from ethanolic hydrochloric acid and 3 : 5 : 6-tribenzyl - 1 : 2-isopropylidene-D-glucofuranose; (2) ethyl-3 : 5 : 6-tribenzoyl-D-glucofuranoside and (4) its 2-acetylation with acetic anhydride; (3) propyl-3 : 5 : 6-tribenzyl-D-glucofuranoside; (5) ethyl - 3 : 5 : 6-trimethyl-D-glucofuranoside, partial separated into a - and b -isomers by distillation; (6) 1 : 3 : 5 : 6-tetrabenzyl-D-glucofuranoside; (7) cyclohexyl 3 : 5 : 6-tribenzyl-D-glucofuranoside; (8) ethyl 3 : 5 : 6-triallyl-D-glucofuranoside; (9) hydroxyethyl-3 : 5 : 6-tribenzyl-D-glucofuranoside and (10) hydroxyethyl-3 : 5 : 6-triallyl-D-glucofuranoside, in both cases using ethylene glycol as reactant; (11) the 2-methyl derivative of (8) using dimethyl sulphate; (12) b :g -dihydroxy propyl-3 : 5 : 6-tribenzyl-D-glucofuranoside (from glycerol); (13) the 2-acetyl derivative of (8); (14) the 2-acetyl or (15) the 2-carboxymethyl derivative of (5); (16) b :g -dihydroxypropyl-3 : 5 : 6-triallyl-D-glucofuranoside and (17) the 2-b -dimethylamino-ethyl derivative of (5) and many of its acid addition salts.  3 : 5 : 6 - Tribenzyl - 1 : 2 - isopropylidene-D-glucofuranose is prepared by reacting 1 : 2-isopropylidene-D-glucofuranose with benzyl chloride in the presence of KOH.  The corresponding trimethyl compound is prepared by step-wise reaction of methyl sulphate with monoacetone glucose; the triallyl compound is similarly prepared using allyl bromide.ALSO:Pharmaceutical preparations comprise one or more D-glucofuranosides of the general formula <FORM:0909278/VI/1> or their 2-0-substituted derivatives in which the 2-substituent is an acyl radical of a carboxylic or sulphonic acid or a substituted or unsubstituted non-aromatic or heterocyclyl-aliphatic hydrocarbon radical, wherein R1 contains at least 2 carbon atoms and represents the organic radical of an alcohol and R3, R5 and R6 each represent the organic radical of an alcohol or an acyl radical of an aromatic or heterocyclic carboxylic acid, or salts of such furanosides that contain a basic or acidic group, the compositions comprising also a pharmaceutical carrier suitable for enteral, parenteral or topical administration.  There may also be present buffering, preserving, stabilizing, wetting or emulsifying agents, and other medicaments, e.g. sulphonamides. Specified furanosides are the: (1) ethyl-3 : 5 : 6-tribenzyl, (2) ethyl-3 : 5 : 6-tribenzoyl, (3) propyl 3 : 5 : 6-tribenzyl, (4) ethyl 3 : 5 : 6-tribenzyl 2-acetyl, (5) ethyl 3 : 5 : 6-trimethyl, (6) 1 : 3 : 5 : 6-tetrabenzyl, (7) cyclohexyl 3 : 5 : 6-tribenzyl, (8) ethyl 3 : 5 : 6-triallyl, (9) hydroxyethyl 3 : 5 : 6-tribenzyl, (10) hydroxyethyl 3 : 5 : 6 - triallyl, (11) ethyl - 2 - methyl - 3 : 5 : 6 - triallyl, (12) dihydroxy propyl 3 : 5 : 6-tribenzyl, (13) ethyl 2-acetyl-3 : 5 : 6-triallyl, (14) ethyl 2-acetyl-3 : 5 : 6-trimethyl, (15) ethyl 2-carboxymethyl 3 : 5 : 6-trimethyl, (16) dihydroxy propyl-3 : 5 : 6-triallyl and (17) ethyl - 2 - (b  - dimethylamino ethyl) - 3 : 5 : 6-trimethyl D-gluco furanosides, the last being described in the form of numerous inorganic and organic acid addition salts.  Many other examples of suitable values of the R symbols and 2-0-substituents are listed.