A process for the preparation of glucosaminyl-epi- podophyllotoxin derivatives

摘要

The invention relates to a process for the preparation of glucosaminyl-epi-podophyllotoxin derivatives of the formula I in which R<1> is hydrogen or the acetyl or a mono-, di- or trihalogenoacetyl protective group, where halogen is fluorine, chlorine or bromine, R<2> is hydrogen or (C1-C4)-alkyl, R<3> is hydrogen, (C1-C4)-alkyl or a benzyloxycarbonyl protective group, R<4> is hydrogen, a mono-, di- or trihalogenoacetyl protective group, a benzyloxycarbonyl protective group or a methyl group and A is C1-C4-alkyl, characterised in that a 3-O-acyl-2-N-benzyloxycarbonyl- 4,6-O-alkylidene-alpha-D-glucosamine derivative of the formula II, which is in the alpha-hydroxy form in which R<1> and R<3> are acyl protective groups as defined above, and R<2> is hydrogen, is reacted with a podophyllotoxin derivative of the formula III in which R<4> is the methyl group or a mono-, di- or trihalogenoacetyl or benzyloxycarbonyl protective group, in the presence of a promoter and of an anhydrous organic solvent at -50 DEG C to 20 DEG C, to give 4-O-(beta-glucosaminyl)-epi-podophyllotoxin derivative of the formula I in which the radicals R<1>, R<2>, R<3> and R<4> have retained their meaning as defined above, and subsequently the glycoside products of the formula I are converted, after elimination of the protective groups, into an amino or dialkylamino compound of the formula I.