# Chemical Synthesis of Bioactive Diterpenoids

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA-IRVINE · 2023 · $426,056

## Abstract

Project Summary
 Polycyclic terpenoid natural products are endowed with a broad range of medicinally relevant biological
activities. Taxol and artemisinin are two premier examples of life-saving terpenoids; the former is used clinically
to treat several different cancers, while the latter is a critical antimalarial agent used worldwide. Chemical
synthesis approaches to natural products provide opportunities to make compounds that might be scarcely
available from nature, to generate analogues that are only available by total synthesis, and to make probe
molecules for increased understanding of the underlying biology. A balance of innovative strategy and new
chemical methodology promises efficient syntheses that can serve to answer important biological questions
that often can only be probed with small molecules.
 As part of our laboratory’s long-term goal to enhance efficiency in the synthesis of complex natural
products to facilitate important studies in biology, the objective of the proposed research program is to develop
concise and creative synthesis designs and empowering methodological advances to permit access to many
bioactive diterpenoid natural products. The rationale for this work is that synthetic chemistry is critical to the
development of natural product “hit molecules” into legitimate preclinical lead compounds by analogue
production, by identification of structure-activity relationships, by the synthesis of chemical probe molecules for
mechanism of action studies, and more. An efficient total synthesis of targeted natural products provides a
platform from which to address each of these key areas of research.
 The proposed research is significant because chemical synthesis will provide access to a broad range of
biologically important secondary metabolites and analogues with which to interrogate key processes; at the
same time, the underlying synthesis designs and methodologies will lead to vertical advancement of the field of
organic chemistry. These contributions are innovative by virtue of the chemistry-driven, multi-faceted
investigations into the biological activity of diterpenoids with immunosuppressive, antiviral, antibiotic, and
neurological activity; the development of new stereocontrolled polyene cyclization strategies to access
polycyclic diterpenoid natural products; and the elaboration of new radical bicyclization strategies to make
complex architectures relevant to bioactive natural products.

## Key facts

- **NIH application ID:** 10691510
- **Project number:** 5R35GM145252-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Christopher D Vanderwal
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $426,056
- **Award type:** 5
- **Project period:** 2022-09-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10691510

## Citation

> US National Institutes of Health, RePORTER application 10691510, Chemical Synthesis of Bioactive Diterpenoids (5R35GM145252-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10691510. Licensed CC0.

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