PROCESS FOR THE PREPARATION OF GLYCOSYLANTHRACYCLINONES

摘要

BEHRINGWERKE AKTIENGESELLSCHAFT 89/B 050 - Ma 812 Dr. Ha/Sd PROCESS FOR THE PREPARATION OF GLYCOSYLANTHRACYCLINONES A process for the preparation of 7-O-glycosylanthracycli-nones which correspond to the following general formula I I is described in which R1 is H or OH R2 is H, ON or OCH3 R3 is H, COOCH3, OH or an O-acyl protecting group R4 is CH2CH3, COCH3, COCH2OH or a COCHaO-acyl protecting group R5 is NH2, an NH-acyl protecting group, OH or an Oacyl protecting group R6 is H, OH, an O-acyl protecting group, NH2 or an NH-acyl protecting group R7 is H, OH or an O-acyl protecting group, an acyl protecting group being an acetyl, mono-, di- or trihaloacetyl group where halogen = fluorine or chlorine, or a benzoyl or p-nitrobenzoyl group, starting from an anthracyclinone compound of the formula II II in which R1 is H or OH R2 is H, OH or OCH3 R3 is H, COOCH3 or an O-acyl protecting group and R4 is CH2CH3, COCH3, or a COCH2-O-acyl protecting group, and a functionalized carbohydrate building block of the formula III III in which R5 is an NH-acyl protecting group or an O-acyl protect ing group R6 is H, an NH-acyl protecting group or an O-acyl protecting group R7 is H or an O-acyl protecting group and R8, R9 and R10 are (C1-C4)-alkyl, an acyl protecting group for amino groups preferably being a trifluoroacetyl group and for hydroxyl groups preferably being an acetyl, trifluoroacetyl, chloroacetyl or p-nitrobenzoyl group, in the presence of a promoter such as trifluoromethanesulfonic acid tri-(C1-C4)alkyl-silyl ester or anhydride or BF3-ether, in an anhydrous organic solvent, if desired in the presence of a base or of an acid entrainer and a drying agent at -50.degree.C to 25.degree.C, a compound of the formula I being formed in which the radicals R1, R2, R3, R4, R5, R6 and R7 retain the meaning defined above and these compounds additionally being subjected to a deacylation step by means of an alkali liquor or an alcoholate for the preparation of cytostatically active compounds of the formula I in which R1 is H or OH R2 is H, OH or OCH3 R3 is H, COOCH3 or OH R4 is CH2CH3, COCH3 or COCH2OH R5 is NH2 or OH R6 is H, OH or NH2 and R7 is H or OH.