Patent ID: 7053191
Filing Date: 2006-05-30
Classification: C07H

Abstract:
1. A process for preparing 4-R-substituted anthracyclines of formula (I) wherein R is defined as hydrogen, a linear or branched oxyalkyl, oxyalkenyl or oxyalkynyl group comprised of one to sixteen carbon atoms, or a ester group COOR 1 ′, wherein R 1 ′ is a linear or branched alkyl, alkenyl or alkyne group of up to ten carbon atoms, and An— is an anion, comprising the steps of: (1) providing 4-demethyldaunorubicin or a derivative of 4-demethyldaunorubicin of formula (II) wherein R 1 comprises H, acyl or acyl halide and R 2 comprises H, acyl or acyl halide, carbonate, or Schiff's base; (2) treating the 4-demethyldaunorubicin or the derivative of 4-demethyldaunorubicin of formula (II) with a sulfonylating agent having a chemical formula R wherein R 3 comprises an alkyl group, alkyl halide group or an aryl group, R 1 comprises hydrogen, acyl, or acyl halide, and R 2 comprises hydrogen, acyl, acyl halide, carbonate, or Schiff's base; (3) reacting the 4-demethyl-4-sulfonyl-daunorubicin of formula (III) with a reducing agent in the presence of catalytic quantities of a compound having formula (N) wherein M represent a transition metal atom; and wherein L and L′ represent the same or different anions or a neutral molecule, and p and q may vary from zero to four, to produce protected 4-demethoxydaunomycin having a formula (V), (4) hydrolyzing the protected 4-demethoxydaunomycin in a basic solution to produce 4-R-substituted anthracyclines of formula (I).