# Total Synthesis of Oxo-Bridged Taxoids and Evaluation of their Anticancer Properties

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $38,974

## Abstract

PROJECT SUMMARY/ABSTRACT
Cancer is a major health crisis with millions of new diagnoses each year. In response, researchers often turn to
nature in search of molecules, often structurally sophisticated, which can serve as viable anticancer therapeutics.
One such molecule is paclitaxel (TaxolÒ), a highly oxygenated diterpenoid belonging to the taxoid family of
natural products. While paclitaxel has proven to be an effective chemotherapeutic, its high lipophilicity and the
emergence of resistant cancer cells pose many therapeutic challenges and create an urgency to study
structurally distinct taxoids, such as taxagifine. Like paclitaxel, taxagifine and its congeners (collectively known
as the oxo-bridged taxoids) possess significant anticancer properties but remain relatively underexplored both
synthetically and biologically, especially with regard to their potential to overcome drug resistance.
Given the urgency to address therapeutic challenges associated with paclitaxel, this proposal aims to establish
the first synthetic approach to oxo-bridged taxoids from the feedstock chemical (S)-carvone, which will enable
comprehensive biological evaluation of these molecules and provide insight into their potential to serve as
alternative treatments to paclitaxel. These studies will be accomplished through three specific aims: 1)
completing the total synthesis of taxagifine, 2) synthesizing additional oxo-bridged taxoids, including analogues,
and 3) assessing their biological activity through collaborative efforts.
The total synthesis of taxagifine and other oxo-bridged taxoids will be pursued through the execution of site-
selective, late-stage functionalizations of a key intermediate, which is prepared convergently from two (S)-
carvone-derived coupling partners using a C–C bond cleavage/cross-coupling strategy. Development of an
efficient and robust synthetic route to taxagifine will set the stage for the synthesis of taxoid analogues, and
ultimately, synthetic work proposed herein will enable not only the preparation of natural and unnatural taxoids,
but will offer new strategies for the synthesis of other highly oxygenated terpenoids as well. Overall, synthetic
and biological investigation of the oxo-bridged taxoids will provide significant insight into these underexplored
molecules, opening the door to the next generation of potential anticancer therapeutics.

## Key facts

- **NIH application ID:** 10221591
- **Project number:** 5F31GM139368-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Melecio Perea
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,974
- **Award type:** 5
- **Project period:** 2020-07-10 → 2022-07-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10221591

## Citation

> US National Institutes of Health, RePORTER application 10221591, Total Synthesis of Oxo-Bridged Taxoids and Evaluation of their Anticancer Properties (5F31GM139368-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10221591. Licensed CC0.

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