A hemisynthesis 'in situ' reaction of (thio)barbituric acids with an α,β-unsaturated aldehyde using perillaldehyde from Ammodaucus leucotrichus essential oil, afforded chromeno-pyrimidine derivatives B-1 and B-2. The reaction was carried out in water and water/ethanol medium without a catalyst. The obtained pyrimidines were identified by their spectral ¹H,¹³C, Dept-135, HMBC, HSQC, COSY, and NOESY 2D. The antioxidant activity of both compounds was evaluated using different in vitro methods (DPPH, ABTS, and CUPRAC). The hemisynthesized molecules exhibited a bacteriostatic effect against ten tested gram (+) and gram (-) strains. According to the molecular docking analysis, B-1 showed lower binding energies compared to B-2 against (PDB: 1HD2) and (PDB: 1KZN) targets, which is in agreement with the ABTS and E. Coli assays. Furthermore, a probable promising anti-HIV activity was noticed against reverse transcriptase (PDB: 2RKI), a key enzyme for HIV replication. The ADME properties calculations showed no Lipinski's rule violation for both compounds.

Transformations of the derivatives of 2-substituted 5-(1,2,3-thiadiazol-4-yl)-3-furoic acid under the action of bases has been studied. In the presence of potassium tert-butylate in THF, the studied compounds decompose with the cleavage of the thiadiazole ring, liberation of nitrogen, and formation of labile acetylene thiolates. In the presence of methyl iodide, these salts form stable 2-methylthioethynylfurans. Under the action of sodium ethylate in ethanol, thiadiazole ring of ethyl [2-methyl-5-(1,2,3-thiadiazol-4-yl)]-3-furoate is split to form the corresponding sodium acetylene thiolate. Under the action of ethanol, two molecules of this salt give bis(furyl)dithiafulvene. In the DMF–potassium carbonate system, acetylene thiolates react with primary and secondary amines giving thioamides of (4-ethoxycarbonyl-5-methylfur-2-yl)acetic acid. Treating of ethyl 2-methyland 2-N-morpholinomethyl-5-(1,2,3-thiadiazol-4-yl)-3-furoates with hydrazine hydrate leads to hydrazinolysis of the ester group and cleavage of thiadiazole ring resulting in the formation of hydrazides of 4-hydrazinocarbonylfur-2-ylacetic acid. In the case of ethyl 2-acetoxymethyl- and 2-(4-nitrophenoxy)methyl-5-(1,2,3-thiadiazol-4-yl)-3-furoates, thiadiazole ring is retained and exclusively hydrazinolysis of the ester groups is observed.

Cyclization of alkyl 2-methyl-5-acetylfuran-3-carboxylate carbethoxyhydrazone according to Hurd-Mori reaction afforded alkyl 2-methyl-5-(1,2,3-thiadiazol-4-yl)-3-carboxylate. Its bromination with N-br...

Reaction of ethyl 2-bromomethyl-5-(1,2,3-thiadiazol-4-yl)furan-3-carboxylate with nucleophiles of different nature was studied. It is shown that substitution of bromine with acetoxy group takes place under the action of sodium acetate in the acetic acid. Stronger bases, like phenolates, cause considerable decomposition of the labile furylthiadiazole fragment Decomposition can be avoided only when this reaction is carried out in the presence of a phase transfer catalyst under the conditions of the ion pair extraction,. In the reaction with sodium ,-diethyl dithiocarbaminate the corresponding thioester is formed. Butanethiol and thiophenol are alkylated as potassium thiolates. In the last case -alkylation proceeds exclusively. Reaction with excess 2-aminoethanol permits to prepare secondary amine, and the reactions with pyrrolidine, piperidine, and morpholine give the corresponding tertiary amines. Phosphorylation with triethyl phosphite under the conditions of Arbuzov reaction leads to the corresponding diethyl phosphonate. In all these transformations furylthiadiazole fragment is retained.