# Synthesis of [3H]muscimol

## TL;DR

This paper presents a new method to synthesize a radioactive form of muscimol, a compound used in neuroscience research, more efficiently and safely.

## Contribution

A novel synthesis method for [3H]muscimol using tritioborane instead of tritiated water is introduced.

## Key findings

- The method achieved a molar activity of 48.3 Ci/mmol (1.79 TBq/mmol) for [3H]muscimol.
- The final product was obtained with >95% radiochemical purity after deprotection.
- The approach avoids the use of bulk tritiated water, making the process safer and more efficient.

## Abstract

Muscimol, a potent GABAA receptor agonist and psychoactive alkaloid found in Amanita mushrooms, is widely used as a tool compound in neurochemical research. Despite its importance, synthetic access to [3H]muscimol of high specific activity has remained limited due to the challenges associated with conventional labeling strategies. Herein, we report a novel synthetic approach for the preparation of [3H]muscimol based on the reduction of a suitably protected amide precursor using in situ generated tritioborane (BT3·THF). The precursor was synthesized in four steps from dimethyl acetylenedicarboxylate, and subsequent electrophilic reduction afforded [3H]benzyl‐protected muscimol in a radiochemical yield of 44 mCi (1.63 GBq) and a molar activity of 48.3 Ci/mmol (1.79 TBq/mmol). Final deprotection with HBr in acetic acid yielded [3H]muscimol·HBr in > 95% radiochemical purity. The method avoids the use of bulk tritiated water employed in established synthetic protocols and enables safe, reliable, and efficient access to this valuable radioligand for applications in GABA receptor studies.

A novel synthetic approach for the preparation of [3H]muscimol (48.3 Ci/mmol, 1.8 TBq/mmol) based on the reduction of a suitably protected amide precursor using in situ generated tritioborane (BT3·THF) is reported. The method avoids the use of bulk tritiated water employed in established synthetic protocols and enables safe, reliable, and efficient access to this valuable radioligand for applications in GABA receptor studies.