# Synthesis of Neurologically Active Small Molecules

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $300,511

## Abstract

Project Summary/Abstract
 The understanding of normal cognitive function and the development of treatments for
neurodegenerative diseases have been enabled by the study of natural products and their synthetic congeners.
The extensive discoveries made in this realm have been limited primarily to the specific activities of abundantly
available natural products or simple derivatives thereof. The long-term goal of this proposal is to use
fragment-coupling approaches to synthesize varied, stereochemically rich, polycyclic natural product
architectures with the potential to further the understanding of neurodegenerative disorders.
 This proposal outlines two convergent approaches for the synthesis of two families of natural
products, the grayanotoxins and the limonoids, both of which have been shown to attenuate neuronal cell
death caused by reactive oxygen species. By departing from conventional strategies that cyclize linear
precursors, this proposal utilizes the convergent and scalable assembly of building blocks into structurally
differentiated scaffolds. In line with conventional approaches, the molecular architectures obtained through
this approach will be subsequently modified through the application of a dehydrogenation methodology
recently reported by our laboratory, as well as by other chemical strategies.
Novel analogs produced by these routes will be evaluated for their ability to alleviate the effects of
reactive oxygen species on neurodegeneration. Through increased understanding of neurodegeneration on a
molecular level, potential avenues for drug discovery and therapeutic intervention will be revealed.

## Key facts

- **NIH application ID:** 10174940
- **Project number:** 5R01GM118614-05
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Timothy Newhouse
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $300,511
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10174940

## Citation

> US National Institutes of Health, RePORTER application 10174940, Synthesis of Neurologically Active Small Molecules (5R01GM118614-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10174940. Licensed CC0.

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