Patent ID: 8846882

Claim:
A method for the production of 4-demethoxydaunorubicin or a salt thereof having the chemical structure of formula (I), wherein An represents an anion, comprising: (a) converting a daunorubicin hydrochloride salt having the chemical structure of formula (II) into a 3′-protected daunorubicin (3′-Prot-daunorubicin) being selected from the group consisting of the compounds having the chemical structures of formulas (III) and (IV), wherein conversion of the 3′-amino group salt to a 3′-azide by contacting with an azide-forming reagent results in formation of (III), and conversion of the 3′-amino group salt to a 3′-trifluoroacetmide by contacting with a trifluoroacetylating reagent results in formation of (IV); (b) demethylating the 3′-Prot-daunorubicin of formula (III) or (IV) by contacting with MgC1 2 (anhydrous) and in the presence of KI (anhydrous) in an anhydrous solvent to yield a 4-demethyl -3′-Prot-daunorubicin being selected from the group consisting of the compounds having the chemical structures of formulas (V) and (VI), respectively, wherein demethylation of (III) results in formation of (V), and demethylation of (IV) results in formation of (VI), wherein the reaction is performed at a reaction temperature in the range of 10-80° C., and in particular in the range of 40-60° C., and wherein the anhydrous solvent is selected from the group consisting of alkanes, cycloalkanes, halogenalkanes, arenes, alkyl oxides, ethers, C 4 -C 6 alcohols, and carbon disulfide; (c) trifluoromethanesulfonylating the 4-demethyl-3′-Prot-daunorubicin of formula (V) or (VI) by contacting with a trifluoromethanesulfonation reagent to yield a 4-O -trifluoromethanesulfonyl -3′-Prot-daunorubicin being selected from the group consisting of the compounds having the chemical structures of formulas (VII) and (VIII), respectively, wherein trifluoromethanesulfonylation of (V) results in formation of (VII), and trifluoromethanesulfonylation of (VI) results in formation of (VIII); (d) reducing the 4O-trifluoromethanesulfonyl-3′-Prot-daunorubicin of formula (VII) or (VIIII) by contacting with a reducing agent to yield a 4-demethoxy-3′-Prot-daunorubicin being selected from the group consisting of the compounds having the chemical structures of formulas (IX) and (X), respectively, wherein reduction of (VII) results in formation of (IX), and reduction of (VIII) results in formation of (X); and (e) removing the protective 3′-Prot group from the 4-demethoxy-3′-Prot-daunorubicin selected from the group consisting of the compound of formula (IX) and the compound of formula (X), wherein the compound of formula (IX) is contacted with an azide-reducing reagent, or the compound of formula (X) is contacted with an alkaline solution, with resulting formation of a 3′-amino group, to yield 4-demethoxy-daunorubicin and, optionally, contacting 4-demethoxydaunorubicin with an acid of formula H+An— to yield 4-demethoxydaunorubicin salt of formula (I).