# New Photocatalytic Coupling Reactions to Prepare Bioactive Molecules

> **NIH NIH R35** · UNIVERSITY OF IOWA · 2024 · $374,454

## Abstract

The overarching goal of this research program is to discover new catalytic methods for the synthesis of
biologically active targets, both natural and unnatural. We have previously reported the synthesis of phenolic
lipid natural products and efforts toward two families of polycyclic terpenes, as well as a general process for
the synthesis of the cobalt complexes used in the photocatalytic investigations described in Project 2. The
targets described in this proposal include molecules that will serve as mechanistic probes to study
neurodegeneration and viral diseases, as well as leads that may provide new therapeutic opportunities. We are
investigating methods to target specific structural motifs with established biological activity, such as amino-adamantanes
and limonoid natural products, as well as catalytic methods designed to apply to a broad
spectrum of chemical targets. The enabling technology behind these methods is photocatalysis, which
harnesses light energy to drive complex catalytic processes. Photocatalysis continues to provide new
mechanisms and transformations that are difficult or impossible to access otherwise. Understanding the
governing principles of these processes allows us to apply that insight to the discovery of new, broadly useful
synthesis methods.
Substituted adamantanes appear in a wide variety of molecules with important function including
clinically approved drugs for Alzheimer’s dementia and viral diseases, however efficient synthesis remains a
challenge. In Project 1, new amino-adamantane derivatives will be accessed through a new aminoalkylation
reaction and new catalytic strategies that enable unique selectivity that is complementary to existing
approaches. The unique strategies described here include a detailed study of the selectivity of new and
established H-atom transfer methods, providing guidelines necessary for selecting the proper HAT catalyst for
different substrate classes. In Project 2, a novel polar/radical crossover manifold inspired by the biochemistry
of vitamin B12 will be developed for the efficient use of inexpensive and readily available alcohols for bioactive
molecule construction. These methods will be applied to the synthesis of promising natural product targets
such as the neuroprotective limonoids. The investigation of the neuroprotective activity of limonoids is of
central importance, therefore alternative pathways will be explored to access to these molecules and
derivatives for mechanism of action studies. Overall, the concepts described here will provide general
platforms for the rapid construction of pharmacophores and bioactive natural product derivatives that can be
immediately deployed by biomedical researchers.

## Key facts

- **NIH application ID:** 10834232
- **Project number:** 5R35GM138050-05
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** David Martin
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $374,454
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834232

## Citation

> US National Institutes of Health, RePORTER application 10834232, New Photocatalytic Coupling Reactions to Prepare Bioactive Molecules (5R35GM138050-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10834232. Licensed CC0.

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