# Synthesis and Optimization of the Aleutianamine Class of Alkaloids

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2022 · $560,675

## Abstract

ABSTRACT
There is a tremendous unmet need for effective synthesis methodologies and strategies for the construction of
aleutianamine and other members of the discorhabdin class of natural products. This has significantly hindered
the mechanistic, basic and applied science studies for this unique class of alkaloids which offers significant value
in the control of a variety of diseases and clearly warrants additional basic research into the synthesis,
mechanism of action and basic pharmacology. Natural Products (NPs) have played a key role as therapeutics
for a variety of diseases and the data presented in this application reveals the tremendous potential for these
molecules. After 25 years of studying marine organisms for new and innovative chemistry we have identified a
single truly remarkable molecule called aleutianamine. Aleutianamine has been recovered from a Latrunculia
sponge collected from the deep ocean off the coast of the Aleutian Islands by NOAA Alaska. We have
exhaustively interrogated extracts for any detectable quantities of this molecule and the only remaining option to
generate mechanistic and in vivo data is to first generate the drug through a reliable synthesis. This molecule is
extremely unique chemically and is a member of two very rare groups of bioactive natural products including the
iminoquinones and the thioalkaloids and is certain to be a product of the extreme conditions of these deep ocean
environments where cold temperatures, high pressure, and anoxic conditions deplete of UV irradiation provides
a unique environment for biosynthesis and rearrangement to form highly unusual molecules. Aleutianamine and
other members of this class as well as their synthetic intermediates offer unique controls for a diversity of
diseases including malaria, inflammation, viral diseases and cancer strongly supporting the development of
strategies to provide consistent supply of the drug and approaches to the generation and diversification of the
class. Due to the rare and limited supply of this molecule the specific aims of this program involve the
development of synthesis methodologies using two different routes in addition to the isolation and
characterization of starting materials and related molecules for SAR and investigations into alternative
approaches involving biosynthetic starting materials for the construction and optimization of the molecule.

## Key facts

- **NIH application ID:** 10345968
- **Project number:** 1R01GM145845-01
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Mark T Hamann
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $560,675
- **Award type:** 1
- **Project period:** 2022-09-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10345968

## Citation

> US National Institutes of Health, RePORTER application 10345968, Synthesis and Optimization of the Aleutianamine Class of Alkaloids (1R01GM145845-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10345968. Licensed CC0.

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