# SYNTHESIS OF ANTHRACYCLINONES

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 1992 · $140,672

## Abstract

A general synthetic strategy, based on the reactions of chromium carbene
complexes with acetylenes, is presented for the synthesis of several
anthracyclinones, anthracyclines, aureolic acid aglycones, and constituents
of antitumor alkaloids.  The synthetic targets include 11-
chlorodaunorubicin, 11-chloroaclacinomycin, and 4-fluoroaclacinomycin which
are unnatural analogs of compounds either in use clinically or currently in
human trials.  The strategy should be flexible enough 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 and if successful, will allow for the
preparation of the unnatural 11-halo analogs for testing.  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 that the key
strategy, the reaction of carbene complexes with acetylenes, be examined
with regard to the synthesis of several 11-deoxy anthracyclines including
aklavinone, 11-deoxydaunomycinone, and 7-con-o-methylnogarol, a
semisynthetic derivative of nogalamycin, which was developed by UpJohn
Company.  Preliminary results indicate that this strategy is flexible
enough to provide for the regioselective synthesis of olivin and
chromomycinone, the aglycones of the aureolic acid family of antitumor
antibiotics related to the anthracyclines.  It has been further found in
preliminary studies that these reactions should provide for an efficient
entry into the aspidospermia carbon skeleton and it is proposed that they
be investigated with regard to the synthesis of several members of the
aspidospermia alkaloid family including vindoline which is a constituent of
the dimeric antitumor indole alkaloids vinblastine and vincristine.

## Key facts

- **NIH application ID:** 3170868
- **Project number:** 5R01CA032974-10
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **SAM.gov UEI:** ZUE9HKT2CLC9
- **Principal Investigator:** WILLIAM Dean WULFF
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $140,672
- **Award type:** 5
- **Project period:** 1983-05-01 → 1994-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170868

## Citation

> US National Institutes of Health, RePORTER application 3170868, SYNTHESIS OF ANTHRACYCLINONES (5R01CA032974-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170868. Licensed CC0.

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