# Chemo-Divergent Cationic Cascades for the Synthesis of Biologically Active Alkaloids

> **NIH NIH F31** · UNIVERSITY OF ROCHESTER · 2022 · $32,036

## Abstract

Project Summary:
Alkaloids are an important class of nitrogen-containing, low-molecular weight compounds
that are ubiquitous in plants.1 These compounds exhibit a wide range of pharmacological
activities; ranging from antineoplastics (like noscapine) to analgesics (like morphine), or
stimulants (like caffeine, or nicotine).2 Given their medicinal properties, the development
of new methodologies that give access to libraries of new and complex alkaloids will aid
in drug discovery efforts. In addition, the newly developed strategies will represent novel
synthetic disconnections, which will facilitate the efficient synthesis of natural products
and drug targets. This proposal will provide a facile and efficient route for the synthesis
of structurally complex alkaloids from simple and inexpensive starting materials. One of
the projects uses a halide-trapped aza-Prins cyclization to form a nitrogen-containing
heterocycle with vinyl halide functional handle. These products can be ionized to give a
series of structurally interesting products, depending on the reaction conditions and
substrate design. The second project involves an intramolecular, π-trapped aza-Prins
cyclization, giving access to two new rings and a new stereocenter in a one pot process.
This chemistry is attractive for asymmetric studies using chiral thioureas to obtain
enantioenriched products. This would be the first example of an enantioselective, alkynyl
Prins cyclization. Synthesized libraries of compounds will be analyzed using online
cheminformatics tools to determine which operationally simple transformations can be
performed to increase the potential for bioactivity in our substrates. These modified
substrates will be submitted to a number of high throughput screening centers for testing
against various cancer cell lines, as well as used in collaborations with the University of
Rochester Medical Center.

## Key facts

- **NIH application ID:** 10388002
- **Project number:** 1F31GM142259-01A1
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Jackson J Hernandez
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $32,036
- **Award type:** 1
- **Project period:** 2022-02-15 → 2024-02-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10388002

## Citation

> US National Institutes of Health, RePORTER application 10388002, Chemo-Divergent Cationic Cascades for the Synthesis of Biologically Active Alkaloids (1F31GM142259-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10388002. Licensed CC0.

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