# Synthesis of Bioactive Natural Products and Unnatural Congeners

> **NIH NIH R35** · FLORIDA STATE UNIVERSITY · 2024 · $366,995

## Abstract

Project Summary/Abstract
 Alkaloid natural products have had an immense impact on the field of therapeutic medicine,
and hold promise for the discovery of new neuropharmacological treatments. One area of
proposed research in the Smith Lab concerns the development of new psychoplastogenic
compounds based on the psychedelic lysergic acid diethylamide (LSD). Although derivatives of
LSD have been explored previously over many decades, derivatives bearing various substitutions
on the indole ring of the ergoline scaffold have never been explored. All of these derivatives are
currently only accessible through total synthesis, and potentially can serve as therapeutic leads
for various neuropsychiatric diseases including Parkinson's disease, PTSD, severe depression,
and addiction. Our concise synthetic approach to the scaffold of LSD hinges on the utilization
and chemical modification of widely available heterocyclic aromatic precursors. This strategy
allows for the exploration of chemical space that would otherwise be inaccessible, however
therapeutically enabling.
 Synthetic inspiration drawn from our route to these LSD analogs has led us to investigate the
synthesis of marine macrocyclic diamine alkaloids such as the halicyclamines and the sarains.
None of these targets have been synthesized previously. Our modular, yet redox-economic
platform for assembling these structurally complex compounds hinges on employing heterocyclic
starting materials at higher oxidation levels to efficiently access their congeners with lower redox
levels. Innovation in this research direction is mainly strategic, demanding a navigation of
synthetic assembly that has not been traversed previously. This will also demand tactical
advances in chemistry that will undoubtedly shed light on novel reactivity patterns that will be
broadly important within the realm of heterocyclic chemistry.

## Key facts

- **NIH application ID:** 10892930
- **Project number:** 5R35GM150795-02
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** Joel Michael Smith
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $366,995
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892930

## Citation

> US National Institutes of Health, RePORTER application 10892930, Synthesis of Bioactive Natural Products and Unnatural Congeners (5R35GM150795-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10892930. Licensed CC0.

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