Synthesis of N‐Acetyl‐D‐ and ‐L‐Leucine‐ 13 C 6 Tool Compounds in Neurodegenerative Disease

Journal article

N‐acetyl‐L‐leucine (levacetylleucine, ALL) is the neuroprotective enantiomer of the racemic antivertigo drug, Tanganil (acetyl‐DL‐leucine, ADLL). ALL has recently been clinically repurposed for the treatment of Niemann Pick disease type C1, a disorder characterised by lysosomal accumulation of glycolipids and cholesterol. Isotopically labelled ALL was required, as well as its negative control, D‐enantiomer (ADL), to monitor the in vivo metabolic fate of the drug and to distinguish it from endogenous leucine and associated metabolites. Here, we describe the synthesis of N‐acetyl‐D‐ and ‐L‐leucine‐13C6, as well as N‐acetyl‐L‐leucine‐13C1, by N‐acetylation of their amino acid precursors, their spectroscopic characterisation and stereochemical and stability studies. These investigations found that formation of the products, as well as their water‐soluble sodium salt formulation, occurs without compromising stereochemical integrity.

Authors: Crepin, D; McGown, A; Shepherd, D; Braine, R; Sharma, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: ChemMedChem
• Volume: 21
• Issue: 9
• Article number: e70295
• Publication date: 2026-05-15
• Acceptance date: 2026-04-22
• DOI: 10.1002/cmdc.70295
• EISSN: 1860-7187
• ISSN: 1860-7179
• Language: English
• Keywords: labelled compound; NPC; amino acid; tool compound