A convenient, ligand-free, Pd(OAc) 2 -catalyzed one-pot reaction has been developed for the synthesis of oxazolines and oxazoles from easily available acid chlorides and propargylamine. The reaction pathways could be easily modulated to selectively obtain oxazolines or oxazoles by merely changing the additives.This method proceeds via in situ sequential nucleophilic addition/elimination reactions followed by an intramolecular 5-exo-dig cycloisomerization reaction. An interesting observation in this case is the effect of an additive: a basic additive such as triethylamine resulted in the formation of 5-methylene oxazolines, while an acidic additive such as acetic acid resulted in the formation of 5-methyloxazoles. With the current protocol we are able to obtain good to moderate yields of the desired product without the need for the isolation of intermediates.Scheme 1 Approach for the synthesis of dihydrooxazoles and oxazoles.
a b s t r a c tTuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) has become the world's leading killer disease due to a single infectious agent which survives in the host macrophage for the indefinite period. Hence, it is necessary to enhance the efficacy of the clinically existing antitubercular agents or to discover new anti antitubercular agents. Here, we report the synthesis, characterization and antimycobacterial evaluation of protein-drug conjugates. A carrier protein, Transferrin (Tf) was covalently conjugated to isoniazid (INH) utilizing hydrazone and amide linkers. The purity of the reactions was confirmed by SDS-PAGE while conjugation was confirmed by UVevisible spectrophotometry, MALDI-TOF analysis, and FTIR spectrophotometry. The in vitro antitubercular assay result showed that the inhibitory activity of the parent drug was conserved in both the conjugates. The conjugates were effective against intracellular Mtb H37Rv and were devoid of cytotoxic effect at therapeutic concentration.
The discovery of antibiotics around the middle twentieth century led to a decrease in the interest in antimycobacterial fatty acids. In order to re‐establish the importance of naturally abundant fatty acid, a series of fatty acid‐thiadiazole derivatives were designed and synthesized based on molecular hybridization approach. In vitro antimycobacterial potential was established by a screening of synthesized compounds against Mycobacterium tuberculosis H37Rv strain. Among them, compounds 5a, 5d, 5h, and 5j were the most active, with compound 5j exhibiting minimum inhibitory concentration of 2.34 μg/ml against M.tb H37Rv. Additionally, the compounds were docked to determine the probable binding interactions and understand the mechanism of action of most active molecules on enoyl‐acyl carrier protein reductases (InhA), which is involved in the mycobacterium fatty acid biosynthetic pathway.
One-Pot Synthesis of Acid Chloride from 1,2-Diols. -The reaction is affected by the amount of tBu-O-Cl, leading to aldehydes or acid chlorides. -(TELVEKAR*, V. N.; MALI, J. K.; DIGHE, M. G.; Synth. Commun. 37 (2007) 5, 865-868; Dep. Pharm. Sci. Technol., Inst. Chem. Technol., Univ. Mumbai, Matunga, Mumbai 400 019, India; Eng.) -H. Haber 31-028
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