# Synthesis and Biological Evaluation of Alkylpiperidine Arenosclerin A.

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2021 · $19,996

## Abstract

PROJECT SUMMARY
The alkylpiperidine alkaloids are a class of natural products isolated from marine sponges possessing diverse
biological activity, including tumor cell cytotoxicity, antimalarial, antitubercular, and antibacterial properties. One
such member of this class of natural products is arenosclerin, which has preliminarily been reported as
possessing antibacterial activity against several antibiotic-resistant clinical isolates and potent cytotoxicity
against several tumor cell lines. While arenosclerin and related family members have preliminarily been
associated with clinically-relevant biological activity, further evaluation has been limited given that these natural
products can only be isolated in small quantities. Providing an efficient synthetic route to access arenosclerin
and related alkaloids would enable further biological study. The tetracyclic structure of arenosclerin consists of
a bis-piperdine core appended to two 17-member peripheral macrocycles. This study proposes an efficient total
synthesis of arenosclerin, which could also be used to synthesize related members of the alkylpiperidine family.
In Aim 1, development of a cycloaddition-fragmentation strategy is described, which would allow access to bis-
piperidinyl ring systems present in several biologically active natural products, including arenosclerin. In Aim 2,
a total synthesis of arenosclerin is proposed whereby a cycloaddition-fragmentation strategy would afford the
target bis-piperidine core, which could then be further elaborated to arenosclerin using a flexible late-stage
cross-coupling strategy to close the two remaining macrocycles. In Aim 3, this proposed study details preliminary
evaluation of the effect of arenosclerin and its synthetic precursors on the growth inhibition of both sensitive and
drug-resistant pathogens. These aims together will provide an efficient route to access arenosclerin, preliminary
data toward investigating one facet of arenosclerin's unique biological activity, and allow for future access and
evaluation of related alkylpiperidine alkaloids.

## Key facts

- **NIH application ID:** 10183273
- **Project number:** 5F31GM134570-03
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Jade Charmaine Williams
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $19,996
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10183273

## Citation

> US National Institutes of Health, RePORTER application 10183273, Synthesis and Biological Evaluation of Alkylpiperidine Arenosclerin A. (5F31GM134570-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10183273. Licensed CC0.

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