Identification of 4-isopropyl-thiotropolone as a novel anti-microbial: regioselective synthesis, NMR characterization, and biological evaluation.

We have synthesized and separated tosylated thujaplicin isomers for the first time, and elucidated their structures using 1D, 2D-NMR techniques and X-ray crystallography. The tosylated isomers were used to synthesize 4-isopropyl-thiotropolone and 6-isopropyl-thiotropolone in a regioselective manner. H and C Chemical shifts of synthesized isomers were fully assigned using several NMR experiments, and their isotropic magnetic shielding was calculated using the GIAO (Gauge Including Atomic Orbitals) method and the B3LYP def2-TZVPP level of theory. The calculated chemical shift values were in a good agreement with the experimental results. The biological activity of all synthesized compounds was evaluated against the fungal pathogen and four different bacterial strains ( (ATCC 29213), (ATCC 35218), and (ATCC 27853)). 4-Isopropyl-thiotropolone was found to inhibit in a low micro molar range and exhibit good therapeutic index and ADME properties. This compound can be used for future lead optimization to design inhibitors against (ATCC 29213).