Room Temperature Accessible Stereospecific Synthesis of Methyl-(Z)-2-(7-methyl-3-oxo-5H-thiazolo[3,2-a]pyrimidin-2(3H)-ylidene)acetates:Cd2+ Fluorescence Probe and DU145 Cell Study.

We designed stereospecific synthesis of Methyl-(Z)-2-(7-methyl-3-oxo-5H-thiazolo[3,2-a]pyrimidin-2(3H)-ylidene)acetates 3(a-t) and explored their application as fluorescent probes for Cd2+ ions for the first time. These analogues were synthesized via one-pot reaction of TDHPM-5-carboxanilides with dimethyl acetylenedicarboxylate in methanol as a reusable green solvent at room temperature. Two new C(sp2)-N, C(sp2)-S sigma bonds, and one new C-N π-bond were formed during this transformation, achieving yields of up to 99%. This protocol demonstrates a low E-factor (0.09 to 0.35), high atom economy (94.83%), and carbon efficiency (142.68%), reflecting a significant advancement in green chemistry. Compound 3a was synthesized in 99% yield on a gram scale. Compound 3p proved to be an excellent fluorescent probe for Cd2+ ions, showing a nine-fold increase in fluorescence intensity. The limit of detection (LOD) and limit of quantification (LOQ) for 3p with Cd2+ ions were 7.5 μM and 25 μM, respectively, with an R2 value of 0.9903. DFT calculations revealed that Cd2+ ions bind effectively in the cavity of 3p through a ligand-to-metal charge transfer mechanism. Cell viability assays and docking studies showed that compounds 3g, 3h, 3p, and 3t exhibited potent activity against the DU145 prostate cancer cell line, with binding affinities of -7.7, -6.8, -8.1, and -7.5 kcal/mol.