# Synthesis of Complex Terpenes From Simple Precursors: Renewal

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $285,135

## Abstract

PROJECT SUMMARY
 From Taxol® to artesunate to retapamulin, complex terpenes have had a profound impact on both the
treatment and understanding of human disease. Despite their enormous medicinal relevance, however, most
complex terpene architectures are not optimal starting points for exhaustive medicinal and chemical biological
studies, and unlike many small molecule drug discovery programs, it is difficult to easily mix- and-match structural
fragments. The proposed research program seeks to discover and develop simple, modular synthetic pathways
to access complex, medicinally relevant terpenoid natural products and determine their protein targets. At the
core of this proposal is the desire to greatly simplify terpene synthesis by using simple isoprene-derived units
and chiral pool materials in concert with novel methodologies and synthetic strategies. The targets chosen for
this program represent both state-of-the-art challenges for complex molecule synthesis as well as potential next-
generation therapeutics ideal for in-depth chemical biological studies. Owing to their potent cytotoxic properties,
complex quassinoid triterpenes have remained attractive targets for decades, yet synthetic routes to these
molecules are lengthy and many members have yet to succumb to syntheses at all. Using novel cross-coupling
methodology we have developed a blueprint for facile access to this family. Cyclized, marine cembranoids
represent a structurally fascinating class of terpene targets with intriguing, yet poorly understood, cytotoxic
activities. Despite much work from numerous laboratories, many flagship members have eluded practitioners of
chemical synthesis for decades. Using a chiral pool building block-based approach and various radical
cyclization strategies, we believe many such targets can be accesses efficiently allowing for their protein targets
to be interrogated using cutting-edge proteomics techniques. Overall this program seeks to use advances in
synthetic chemistry to construct rare, biologically active terpenes with high efficiency allowing interrogation of
their anti-cancer properties and protein targets. In the process of this work, students will be provided with rigorous
and intellectually stimulating training in synthetic chemistry.

## Key facts

- **NIH application ID:** 10808908
- **Project number:** 5R01GM116952-09
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Thomas John Maimone
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $285,135
- **Award type:** 5
- **Project period:** 2016-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10808908

## Citation

> US National Institutes of Health, RePORTER application 10808908, Synthesis of Complex Terpenes From Simple Precursors: Renewal (5R01GM116952-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10808908. Licensed CC0.

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