Patent ID: 8802830
Filing Date: 2014-08-12
Classification: C07H

Abstract:
1. 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 AcX is defined by the combination of Ac and X, wherein Ac=AlkCO, OC—(CH wherein the strong base is a cyclic or polycyclic tertiary amine represented by NR (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 (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),