ApplicationNo. 05/649225 filed on 01/15/1976
US Classes:552/201, Two oxygens double bonded directly to the interior ring in para positions536/6.4, Daunomycin or derivative549/419, Nitrogen attached directly or indirectly to the hetero ring by acyclic nonionic bonding558/427, Polycyclo ring system having at least three cyclos, at least one of which is a benzene ring560/227Fluorine in acid moiety
ExaminersPrimary: Helfin, Bernard
Assistant: Reamer, James H.
Attorney, Agent or Firm
AbstractA process for the synthesis of adriamycin and 7,9-epiadriamycin, both active antineoplastic agents, in which 7-deoxydaunomycinone, in either the 9s or racemic (b1;) form, is employed as the starting material, the process in one embodiment also being productive of the useful intermediate compound 4-methoxy-6,11-dihydroxy-7,8-dihydro-5,9(10H),12-naphthacenetrione. The process involves converting 7-deoxydaunomicinone successively to daunomycinone, adriamycinone, 14-0-p-anisyldiphenylmethyladriamycinone and finally to adriamycin or to both adriamycin and 7,9-epiadriamycin. When producing the latter mixture of diastereomers, the 7-deoxydaunomycinone starting material is first converted to racemate form by a process involving the successive production of 7-deoxydaunorubicinol, 4-methoxy-6,11-dihydroxy-7,8-dihydro-5,9(10H), 12-naphthacenetrione, (b1;)-4-methoxy-9-cyano-6,9,11-trihydroxy-7,8,9,10-tetrahydro-5,12-naphth acenedione, (b1;)-4-methoxy-9-cyano-9-(2'-tetrahydropyranyloxy)-6,11-dihydroxy-7,8,9, 10-tetrahydro-5,12-naphthacenedione and (b1;)-7-deoxydaunomycinone.