Novel 4H-pyrimido[2,1-b]benzothiazoles derivatives: Camphorsulphonic acid catalyzed enantioselective synthesis, optimization, and biological study

Abstract

An efficient, highly convergent route for the synthesis of novel fourteen single isomer derivatives of ethyl-2-methyl-4-(pyridin-2-yl)-4H-benzo[4,5]thiazolo[3,2-a]pyrimidine-3-carboxylate have been developed by one-pot, three-component reaction between pyridine 2-aldehyde, β-ketoester and various derivatives of 2-amino benzothiazole in the presence of D-(+)-10-camphorsulphonic acid (D-(+)-10-CSA) as an effective chiral acid catalyst. Under the optimized conditions with 20 mol% catalyst loading, a wide range of optically active 4H-pyrimido[2,1-b]benzothiazole derivatives were obtained in good yields (up to 82%) with good to excellent enantioselectivities (84-99%ee). Their structures were elucidated by various spectroscopic methods such as ¹H-NMR, ¹³C-NMR, Chiral HPLC, mass and elemental analysis. The attractive feature of this approach is one-pot synthesis, good yield, environment benign, mild reaction condition, simple, efficient, excellent stereoselectivity, water soluble catalyst and easy workup. All the final scaffolds have been screened for antibacterial activity. Among them, 4a’, 4c’, 4d’, 4e’, 4f’, 4g’, 4j’,4m’ and 4n’ were proven to possess enhanced antibacterial properties as compared to the standard drug.

Graphic Abstract

KEYWORD:

• 2-Amino benzothiazole
• asymmetric synthesis
• camphorsulphonic acid
• fused heterocyclic compound
• multi component reactions (MCR)

Acknowledgements

The authors are thankful for UGC-Info net and INFLIBNET Gujarat University for providing e-source facilities. The authors are thankful to Dr. Y. S. Patel, Principal, Government Science College, Limkheda and the Department of Chemistry, Gujarat University for providing the necessary facilities. The authors (M.N.B) and (M.A.B) are thankful to the UGC-BSR fellowship for financial support.

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:

Conflict of interest

The authors have declared that there is not any conflict of interest.

Author contributions

The manuscript was written through the contributions of all authors. All authors have approved the final version of the manuscript.