# Method and Strategy Development for the Synthesis of Physiologically Important Natural Products

> **NIH NIH R01** · BAYLOR UNIVERSITY · 2021 · $297,775

## Abstract

PROJECT SUMMARY/ABSTRACT
Over the past three decades, 28% of all new FDA approved drugs have been natural products, or derived from
natural products, while 27% have been entirely synthetic in origin. Thus, the pursuit of new synthetic methods
and strategies to access complex molecules is not only a worthy pursuit, but a critical component of biomedical
research and drug development that also contributes novel elements of synthetic strategy and methods to the
lexicon of synthetic chemistry. The studies proposed within this application describe the pursuit of six different
natural products that fall into three general classes (diketopiperazine, alkaloid, and terpenoid). These
compounds possess a range of biological activities including: leishmanicidal, NO production inhibition, anti-
inflamatory, antiinsectan, antifungal, antiviral, cytotoxicity against a variety of cancer cell lines, as well as anti-
proliferative activity. For the diketopiperazine and alkaloid projects we are aiming to develop ring expansion
technology that will enable efficient access to imbedded hydroxamic acid intermediates. More specifically: Aim
1, entails syntheses of the N-hydroxy-2,5-diketopiperazine-derived (NHDKP) natural products haenamindole,
raistrickindole A, and 14-hydroxyterezine D. This aim also includes the development of a regioselective ring
expansion of tetramic acids that will enable the direct acces of to highly functionalized NHDKP’s. Aim 2
focuses on syntheses of phyllantidine and flueggeacosine B, two members of a securinega alkaloid subset that
contain N-O bonds. The scope of the optimized ring-expansion chemistry developed in Aim-1 will be expand in
this aim to deliver key intermediates in both syntheses. Aim 3 is a departure from aims 1 and 2 and turns
toward further development of keteniminium chemistry by its application in a complex synthetic setting. At
present, work toward each aim is at a different stage of development and this development will continue to
evolve over the course of the grant period. As with all of our synthetic endeavors, collections of intermediates
will be submitted to the NIH for SAR studies and once materials are in hand further collaborations are sought.
In addition to direct contributions to biomedical science afforded by the latter, our synthetic efforts have (and
will continue to) educate graduate students and postdoctoral researchers in the planning and execution of
complex molecule synthesis.

## Key facts

- **NIH application ID:** 10132361
- **Project number:** 5R01GM136759-02
- **Recipient organization:** BAYLOR UNIVERSITY
- **Principal Investigator:** JOHN L WOOD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $297,775
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132361

## Citation

> US National Institutes of Health, RePORTER application 10132361, Method and Strategy Development for the Synthesis of Physiologically Important Natural Products (5R01GM136759-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10132361. Licensed CC0.

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