Patent ID: 8802830

Claim:
A method of preparing an anthracyclin having a formula represented by Formula (1) comprising: (a) providing N-Trifluoroacetyl-13-daunorubicinol represented by Formula (4); (b) reacting the N-Trifluoroacetyl-13-daunorubicinol with dimethylsulfoxide (DMSO) activated by an acylating agent, in an aprotic solvent, to produce an intermediate sulfoxy salt and treating the intermediate sulfoxy salt with a strong base to produce 4-′-keto-N-Trifluoroacetyldaunorubicin of Formula (5); wherein the aprotic solvent is selected from the group consisting of DMSO, DMAA, HMPA, Acetonitrile, DCM, halogenalkanes, aromatic hydrocarbons, and mixtures thereof; wherein the acylating agent is represented by AcX, wherein: AcX=PySO 3 , SOCl 2 , PHal 3 , POHal 3 , wherein Hal=Cl, Br; or AcX is defined by the combination of Ac and X, wherein Ac=AlkCO, OC—(CH 2 )—CO, n=0-4; AlkSO 2 , ArCO, or ArSO 2 ; wherein Alk=alkyl of halogenalkyl radical; and Ar=phenyl or substituted phenyl radical; and X═Cl, Br, I, OAc; wherein the strong base is a cyclic or polycyclic tertiary amine represented by NR 7 R 8 R 9 , wherein R 7 , R 8 , and R 9 =alkyl or cycloalkyl, and wherein, if R 8 , R 9 =cycloalkyl, then R 8 together with R 9 simultaneously=—(CH 2 ) where n=3-6; (c) reacting the 4′-keto-N-Trifluoroacetyldaunorubicin with a borohydride of an alkaline metal to produce N-Trifluoroacetyl-4′-epi-daunorubicin represented by Formula (6); (d) hydrolyzing N-Trifluoroacetyl-4′-epi-daunorubicin in a basic solution to produce a compound represented by Formula (7); wherein An − is an anion of a strong acid; (e) reacting the compound represented by Formula (7) with a halogenizing agent represented by Formula (8), wherein R 1 through R 6 are defined as at least one of H or a hydrocarbon radical of 1 to 4 carbon chains (C 1 -C 4 ) and Hal is Cl, Br, or I, to form a compound represented by Formula (9), wherein Hal is Cl, Br, or I, and An− is an anion of strong acid; and (f) hydrolyzing the compound represented by Formula (9) in the presence of a formate of an alkaline metal to produce an anthracyclin having a formula represented by Formula (1),