# Synthesis of Complex Terpenes From Simple Precursors

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $69,961

## Abstract

Summary of Parent Award (R01GM116952)
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:** 10387530
- **Project number:** 3R01GM116952-06S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Thomas John Maimone
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $69,961
- **Award type:** 3
- **Project period:** 2016-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10387530

## Citation

> US National Institutes of Health, RePORTER application 10387530, Synthesis of Complex Terpenes From Simple Precursors (3R01GM116952-06S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10387530. Licensed CC0.

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