PROCESSO PARA A PREPARACAO DE GLICOSIL-ANTRACICLINONAS

• Main Author: CENEK KOLAR
• Format: Patent
• Language: Portuguese
• Published: 30.09.1991
• Edition: 5
• Subjects: APPARATUS THEREFOR; CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOIDCHEMISTRY; CHEMISTRY; DERIVATIVES THEREOF; GENERAL METHODS OF ORGANIC CHEMISTRY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; NUCLEIC ACIDS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC CHEMISTRY; PERFORMING OPERATIONS; PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SUGARS; THEIR RELEVANT APPARATUS; TRANSPORTING

A process is described for the preparation of 7-O-glycosylanthracyclinones which correspond to the following general formula I in which the radicals denote R H or OH R H, OH or OCH3 R H, COOCH3, OH or O-acyl protective group R CH2CH3, COCH3, COCH2OH or COCH2O-acyl protective group R NH2, NH-acyl protective group, OH or O-acyl protective group R H, OH, O-acyl protective group, NH2 or NH-acyl protective group R H, OH or O-acyl protective group where an acyl protective group is an acetyl, mono-, di- or trihaloacetyl group with halogen representing fluorine or chlorine, or a benzoyl or p-nitrobenzoyl group, starting from an anthracyclinone compound of the formula II in which R is H or OH R is H, OH or OCH3 R is H, COOCH3 or O-acyl protective group and R is CH2CH3, COCH3, COCH2-O-acyl protective group and a functionalised carbohydrate building block of the formula III in which R is NH-acyl protective group or O-acyl protective group R is H, NH-acyl protective group or O-acyl protective group R is H, O-acyl protective group and R , R and R are (C1-C4)-alkyl where an acyl protective group for amino groups is preferably a trifluoroacetyl group and for hydroxyl groups is preferably an acetyl, trifluoroacetyl, chloroacetyl or p-nitrobenzoyl group, in the presence of a promoter such as trifluoromethanesulphonic acid tri-(C1-C4)-alkylsilyl ester or anhydride or BF3-ether, in an organic anhydrous solvent, where appropriate in the presence of a base or of an acid trap and of a desiccant at -50 DEG C to 25 DEG C, producing a compound of the formula I in which the radicals R , R , R , R , R , R and R retain the meaning defined above, and these compounds then being deacylated by means of an alkali metal hydroxide solution or of an alcoholate to prepare cytostatic compounds of the formula I in which R is H or OH R is H, OH or OCH3 R is H, COOCH3 or OH R is CH2CH3, COCH3 or COCH2OH R is NH2 or OH R is H, OH or NH2 and R is H or OH.