The pulmonary infection tuberculosis (TB), popularly thought of as a disease of a bygone era, and once known as “consumption”, is very much on the rise with a global epidemic of drug-resistant strains threatening our health today. Latent, asymptomatic TB is endemic and as a co-infection with HIV an increasingly worrying health issue particularly in the developing world. Antibiotics used against TB were developed more than four decades ago.
Chemists at the University of Minnesota, USA, have now developed a useful total synthesis of transvalencin Z (pictured), originally derived from the fungi-like bacterium Nocardia transvalensis. The compound is relatively potent and selective against Mycobacterium smegmatis, which the team says makes it an attractive target for structure–activity studies in research to treat the related species M. tuberculosis; its mode of action should be very different from those old antibiotics. Its absolute configuration has also been defined using the synthesis, chromatographic retention times, and optical rotation experiments.
- Total Synthesis and Biological Evaluation of Transvalencin Z,
K. M. Nelson, C. E. Salomon, C. C. Aldrich,
J. Nat. Prod. 2012.
DOI: 10.1021/np200972s
Based on the paper reported by Aldrich and coworkers, the synthetic Transvalencin Z and other 3 diasteromers failed to exhibit any inhibitory activity against a panel of microbial pathogens, including several species of mycobacteria. Any way, it’s a great effort by Aldrich for disclosing the synthesis and biological studies of synthetic molecules.