# LIGNAN ANTITUMOR PROTOTYPES VIA DIANION INTERMEDIATES

> **NIH NIH R01** · UNIVERSITY OF CINCINNATI · 1987 · $52,780

## Abstract

The specific goal of this proposal is the synthesis of a series of
increasingly challenging lignan natural products culminating in the
efficient preparation of two antitumor prototypes:  steganacin and
podophyllotoxin.  Development of such sequences should prove especially
useful for exploration of structure-activity relationships among analogs to
these promising agents.

Dianion intermediates exhibit extraordinary reactivity towards
electrophiles.  Preliminary studies have demonstrated that carboxylic acid
dianions can be either dimerized or iodinated simply by varying the
stoichiometry of added I2.  Building upon this simple transformation,
numerous symmetrically- and unsymmetrically-submitted succinic acid
derivatives (including anhydrides, lactones, and amides) become readily
available.

Key synthetic steps to be explored in the generation of both steganacin and
podophyllotoxin include reaction of amide dianions with 2-iodocarboxylates,
selective reduction of the resulting acid-amide products, and
intramolecular photochemically-driven iodination using N-iodoamide
precursors.

## Key facts

- **NIH application ID:** 3179644
- **Project number:** 5R01CA040105-03
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **SAM.gov UEI:** DZ4YCZ3QSPR5
- **Principal Investigator:** JOHN L BELLETIRE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $52,780
- **Award type:** 5
- **Project period:** 1985-09-30 → 1989-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179644

## Citation

> US National Institutes of Health, RePORTER application 3179644, LIGNAN ANTITUMOR PROTOTYPES VIA DIANION INTERMEDIATES (5R01CA040105-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179644. Licensed CC0.

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