# Fluoroalkylethers and Fluorinated Ethermimetics

> **NIH NIH R35** · PURDUE UNIVERSITY · 2020 · $375,488

## Abstract

PROJECT SUMMARY
Fluoroalkyl ethers and thioethers are important for medicinal chemistry, serving as both active pharmaceutical
ingredients and biological probes. Therefore, the ability to access these fluorinated substructures is critical for
the development of new therapeutics. Despite recent synthetic improvements that improve access to many
fluorinated substructures, the community has not generally addressed the preparation of fluoroalkyl
(thio)ethers. Thus, mild, convergent, and practical procedures for accessing these substructures are still
lacking, which restricts access to new biological probes and therapeutic candidates. The Altman group aims to
overcome the aforementioned limitations by developing new methods and general strategies for accessing
fluoroalkyl (thio)ethers directly from simple and ubiquitous alcohol- and thiol-based substrates. More
specifically, the proposed work will employ base-catalyzed nucleophilic addition reactions to C–C bonds to
access a variety of biomedically important fluoroalkylether substructures. Development of the proposed
strategies will enable medicinal chemists to access new and unique biological probes and therapeutics.
The recent surge in synthetic organofluorine chemistry has provided a plethora of new methods capable of
generating many new fluorinated substructures. In many cases, the creativity of the synthetic chemists for
generating these fluorinated substructures has exceeded the experimentally validated uses of these new
fluorinated groups. In fact, some synthetic chemists have proposed replacing synthetically challenging
fluoroalkyl ethers and metabolically instable non-fluorinated ether substructures with more readily accessible
fluorinated ethermimetics. However, no in silico, in vitro and in vivo data supports these claims. The Altman
group aims to experimentally characterize the physicochemical and biophysical perturbations imparted by the
proposed fluorinated ethermimetics using a combination of computational, physicochemical, in vitro and in vivo
methods. This experimental data will enable medicinal chemists to rationally integrate these emerging
fluorinated substructures in therapeutic candidates.

## Key facts

- **NIH application ID:** 9978833
- **Project number:** 5R35GM124661-05
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Ryan A Altman
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $375,488
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978833

## Citation

> US National Institutes of Health, RePORTER application 9978833, Fluoroalkylethers and Fluorinated Ethermimetics (5R35GM124661-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9978833. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*