A method of synthesizing R1, R2-substituted-4' (ax. or eq.)-OH
anthracyclines and their corresponding salts of Formula (1) from
daunorubicin or N-Trifluoroacetyl-4-R1-derivatives of daunorubicin,
wherein R1 is defined as H, OH, and 4'-HO is defined as ax[ial]. The
method includes producing N-Trifluoroacetyl daunorubicin and treating the
N-Trifluoroacetyldaunorubicin or N-Trifluoroacetyl-4-R.sub.1-derivatives
of daunorubicin, wherein R.sub.1 is defined as H, OH, with
dimethylsulfoxide activated by different acylating agents. The attained
intermediate product is then treated with a strong base (ex. tertiary
amines) resulting in the 4'-keto-N-Trifluoroacetyl-4-R.sub.1 daunorubicin
wherein R.sub.1 is defined as H, OH, OMe. The
4'-keto-N-Trifluoroacetyl-4-R.sub.1-daunorubicin is reacted with a
reducing agent, a derivative of a borohydride of an alkaline metal
MHBL.sub.3 , to produce N-Trifluoroacetyl-4'-epi-4-R.sub.1-daunorubicin.
The N-Trifluoroacetyl-4'-epi-4-R.sub.1-daunorubicin undergoes hydrolysis
in a basic solution to produce a derivate of an anthoacyclin which is
halogenized [by complex halogenides] to form a 14-Hal-derivative. This
result is then hydrolyzed by well-known methods in the presence of a
formate of an alkaline metal to form the desired final compound.