Bedaquiline (BDQ) was administered to healthy Sprague-Dawley rats in order to determine its localisation in the brain using mass spectrometry imaging (MSI). This study shows that BDQ has the potential for targeting TB reservoirs in the CNS.

Bedaquiline (BDQ) is the most critical pharmaceutical in the world for treating multidrug-resistant Mycobacterium tuberculosis. Despite it being highly effective, BDQ asymmetric synthesis remains a challenge. Herein, the influence of chiral bases, namely, bis­(1-phenylethyl)­amine, bisoxazoline, and sparteine on the diastereoselective lithiation reaction to obtain BDQ was investigated. The highest diastereoselective ratio (dr) emerged as 90:10 from the (+)-bis­[(R)-1-phenylethyl] lithium amide. This is a significant improvement from the 50:50 dr achieved from the commercial synthesis. Thereafter, the desired (90:10 RS, SR) diastereomeric mixture was easily isolated via a gravity column and subjected to chiral supercritical fluid chromatography (SFC) to access the desired enantiomer (1R, 2S)-BDQ. The advantages of this procedure are enhanced diastereoselection as well as a greener, faster way to achieve excellent enantioseparation (up to 1.0 g scale).

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