SYNTHESIS OF ANTHRACYCLINONES

NIH RePORTER · NIH · R01 · $127,040 · view on reporter.nih.gov ↗

Abstract

A general synthetic strategy is presented for the synthesis of several anthracyclinones based on the reactions of chromium carbene complexes with acetylenes. The synthetic targets include the aglycones of daunorubicin and adriamycin which are important chemotherapeutic agents for the treatment of a broad range of human cancers. The strategy is flexible to allow for the synthesis of both the 11-oxy and the 11-deoxy anthracyclinones and we propose to develop from it a convergent synthesis for these two major classes of anthracyclinones. The 11-deoxy anthracyclinones have been of more recent interest due to the finding that some members of this class have comparable activity to that of adriamycin but with a reduced level of cardiotoxicity. It is proposed to synthesize the aglycone of aclacinomycin and 7-con-o-methylnogarol, a semi-synthetic derivative of nogalamycin, which was developed by UpJohn Company. This compound, now known as menogarol, has recently been approved for phase II of human clinical trials. Preliminary results indicate that this strategy is flexible enough to provide for the regioselective synthesis of several unnatural mono fluoro derivatives of aklavinone.

Key facts

NIH application ID
3170865
Project number
5R01CA032974-06
Recipient
UNIVERSITY OF CHICAGO
SAM.gov UEI
ZUE9HKT2CLC9
Principal Investigator
WILLIAM Dean WULFF
Activity code
R01
Funding institute
NIH
Fiscal year
1988
Award amount
$127,040
Award type
5
Project period
1983-05-01 → 1989-04-30