# Development and Exploitation of New Synthetic Strategies for Tropolones

> **NIH NIH SC1** · BROOKLYN COLLEGE · 2020 · $377,754

## Abstract

Project Summary and Abstract
 Troponoids are naturally occurring aromatic 7-membered rings that, despite being well-known to chem-
ists, are highly underexploited in medicinal chemistry studies, and more broadly in the development of func-
tional small-molecules. This can be largely tied to the challenges associated with their synthesis, and a lim-
ited appreciation for how their unique properties could be leveraged in molecular design. The broader ob-
jective of the current proposal is to develop new tools and knowledge related to troponoids, with an empha-
sis on their utility biomedically. Aim 1 will exploit the broad herpesvirus antiviral activity of
α-hydroxytropolones in a `kick-and-kill' strategy for Kaposi's sarcoma-associated herpesvirus (KSHV).
Specifically, we will optimize α-hydroxytropolones as inhibitors of the C-terminal domain of KSHV ORF29.
As part of this aim, we will also carry out optimization studies on a newly identified KSHV lytic activator that
binds to KSHV PAN ENE. Aim 2 will explore an oxidopyrylium cycloaddition/ring-opening approach to
4-hydroxytropolones. This aim will advance knowledge related to 3-hydroxy-4-pyrone-based oxidopyrylium
cycloaddition chemistry, and also provide a new and efficient route to pyran-fused tropolones, which is a
structural feature that exists in various bioactive natural products, including the potent anti-cancer molecule
pycnidione. Finally, aim 3 will explore a Büchner ring-expansion/ air oxidation approach to tropolones,
which will be used in target-oriented synthesis towards molecules such as the antimalarial natural product
puberulonic acid. This aim at its core will revisit an exceptionally efficient method to generate tropolones
that was studied over half a century ago. We will improve the procedure by leveraging an efficient air oxida-
tion process recently discovered in our lab, and study substrate and catalyst control on the regioselectivity
of arene cyclopropanation. The completion of these aims are expected to highlight the biomedical potential
of troponoid as a drug fragment, refine synthetic strategies previously developed in our lab, establish new
methods for tropolone synthesis, and advance knowledge related to the associated chemical reactions,
such oxidopyrylium cycloaddition and cyclopropanation chemistry.

## Key facts

- **NIH application ID:** 9855265
- **Project number:** 2SC1GM111158-05
- **Recipient organization:** BROOKLYN COLLEGE
- **Principal Investigator:** Ryan Murelli
- **Activity code:** SC1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $377,754
- **Award type:** 2
- **Project period:** 2015-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9855265

## Citation

> US National Institutes of Health, RePORTER application 9855265, Development and Exploitation of New Synthetic Strategies for Tropolones (2SC1GM111158-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9855265. Licensed CC0.

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