# A Synthesis Platform to Leverage the Neuroscience Potential of Yohimbine Alkaloids

> **NIH NIH R21** · NORTHWESTERN UNIVERSITY · 2020 · $418,284

## Abstract

PROJECT SUMMARY
Natural products are unique sources of new lead compounds for the understanding and ultimate treatment
of neurological disease. This proposal focuses on the synthesis and biological characterization of
promising new small molecules based on the privileged yohimbine alkaloid scaffold. While these complex
natural product alkaloids have been academic targets for synthesis over multiple decades, there is still a
surprising lack of efficient, <10 step routes to provide new analogs of these classes of compounds
containing high degrees of stereochemical information. Consequently, this dearth has limited the
exploration of many yohimbine classes in discovery-based screening of CNS targets and represents a
major gap in the knowledge. This high risk, high reward project will support both target and focused library
synthesis of new privileged molecules and initial screening/validation of CNS activity in collaboration with a
GPCR expert. This proposal brings together the complementary natural products chemistry and
neuropharmacological expertise of the Scheidt and McCorvy laboratories. The objectives will be to: (1)
synthesize mitragynine to establish the shortest route yet to this compound, and (2) create new
mitragynine and yohimbine-like compounds and explore their potential as agonists and/or antagonists in
CNS biology. This project will yield novel chemical tools for the pharmacological manipulation of CNS
receptors and may lead to new therapeutic strategies for pain management and neurological diseases.

## Key facts

- **NIH application ID:** 10143006
- **Project number:** 1R21NS120521-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Karl A Scheidt
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $418,284
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10143006

## Citation

> US National Institutes of Health, RePORTER application 10143006, A Synthesis Platform to Leverage the Neuroscience Potential of Yohimbine Alkaloids (1R21NS120521-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10143006. Licensed CC0.

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