Synthesis of adriamycin and 7,9-epiadriamycin

Patent 4012448 Issued on March 15, 1977. Estimated Expiration Date:

March 15, 1994. Estimated Expiration Date is calculated based on simple USPTO term provisions. It does not account for terminal disclaimers, term adjustments, failure to pay maintenance fees, or other factors which might affect the term of a patent.

Abstract Claims Description Full Text

Patent References

3019260

3102914

3590028

3803124

3862225

Inventors

Assignee

Stanford Research Institute

Application

No. 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

Examiners

Primary: Helfin, Bernard
Assistant: Reamer, James H.

Attorney, Agent or Firm

De Witt; Donovan J.

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 (&#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.