Stereoselective synthesis of trans-3-functionalized-4-pyrazolo[5,1-b]thiazole-3-carboxylate substituted β-lactams: Potential synthons for diverse biologically active agents

Abstract

An efficient protocol for the stereoselective synthesis of pyrazolo[5,1-b]thiazole-3-carboxylate tethered β-lactam conjugates 8a–j from novel pyrazolo [5,1-b]thiazole-3-carboxylate substituted Schiff’s bases 6a–f is reported here. The reaction between various ketene precursors and novel Schiff’s bases 6a–f afforded exclusive formation of trans-β-lactams 8a–j. The substrate scope of this approach was investigated extensively by varying different groups (R, Z). All the novel compounds were characterized using various spectroscopic techniques, such as FT-IR, ¹H NMR, ¹³C NMR, elemental analysis, ¹³C NMR (DEPT-135), and mass spectrometry in representative cases. Single crystal X-ray crystallographic study of trans-ethyl 7-(1-(4-methoxyphenyl)-4-oxo-3-phenoxyazetidin-2-yl)-6-methyl-2-(methylthio)pyrazolo[5,1-b]thiazole-3-carboxylate 8a has confirmed the molecular structure and the stereochemical outcome. To the best of our knowledge, the synthesis of such types of Schiff’s bases and β-lactam conjugates has not been reported so far.

Graphical Abstract

Keywords:

• Cycloaddition
• pyrazolo[51-b]thiazole-3-carboxylate
• single crystal X-ray
• stereoselective
• trans-β-Lactams

Additional information

Funding

AB gratefully acknowledges the financial support for this work from the Department of Science and Technology (DST), New Delhi, Government of India, Project No. SR/FT/CS-037/2010 dated 28-10-2010, FIST-II/PURSE-II (DST) and UGC-CAS, Panjab University, Chandigarh. SB and PY acknowledges the financial support from University Grant Commission (UGC), New Delhi vide Award No. 201112-RGNF-ST-HIM-9284 and 58/(OBC) (CSIR-UGC NET 2016), respectively.