# SYNTHESIS OF COCARCINOGENIC DITERPENES

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 1992 · $110,298

## Abstract

This proposal outlines a novel strategy for the total synthesis of
typical members of the irritant and cocarcinogenic ingenane and tigliane
classes of diterpenes.  These compounds have been isolated from certain
species of the genus Euphorbia.  Derivatives of these compounds have
received considerable attention recently, particularly in terms of
examining tumor promotion and related studies.

The unusual ingenane carbon skeleton exhibited by these compounds is
characerized by a bicyclo [4.4.1]undecane ring system fused to a
cyclopentenol moiety.  The approach proposed for entry into this system
will focus on a novel application of a thermal [6+4] cycloaddition
between a suitably substituted diene partner and tropone.  Subsequent
annulation of the fused five-membered ring would complete the
construction of the basic architecture of the molecule in a
stereoselective fashion.  Adjustment of the various oxidation levels
around the periphery of the compound would lead to ingenol the parent
diterpene from which other medicinally important derivatives will be
prepared.

Synthetic approaches to phorbol and related species will also be
investigated.  The novel 5-7-6 tricyclic ring system of these compounds
will be assembled from a rigid hydroazulenic precursor.  Application of
this strategy of the preparation of several phorbol derivatives is
planned.

## Key facts

- **NIH application ID:** 3174178
- **Project number:** 5R01CA036543-06
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **SAM.gov UEI:** M6K6NTJ2MNE5
- **Principal Investigator:** JAMES H RIGBY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $110,298
- **Award type:** 5
- **Project period:** 1988-12-01 → 1993-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174178

## Citation

> US National Institutes of Health, RePORTER application 3174178, SYNTHESIS OF COCARCINOGENIC DITERPENES (5R01CA036543-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174178. Licensed CC0.

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