Synthesis of adriamycin and 7,9-epiadriamycin

US4012448A · kind A · utility

Assignee

• Stanford Research Institute · US

Inventors

• Thomas H. Smith · East Palo Alto, US
• Allan N. Fujiwara · Sunnyvale, US
• David W. Henry · Chapel Hill, US
• William W. Lee · Arcadia, US

Key dates

• Filing date: Jan 15, 1976
• Grant date: Mar 15, 1977
• Expiry date: Jan 15, 1996

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D309/12
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

A process for the synthesis of adriamycin and 7,9-epiadriamycin, both active antineoplastic agents, in which 7-deoxydaunomycinone, in either the 9s or racemic (.+-.) 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, (.+-.)-4-methoxy-9-cyano-6,9,11-trihydroxy-7,8,9,10-tetrahydro-5,12-naphth acenedione, (.+-.)-4-methoxy-9-cyano-9-(2'-tetrahydropyranyloxy)-6,11-dihydroxy-7,8,9, 10-tetrahydro-5,12-naphthacenedione and (.+-.)-7-deoxydaunomycinone.