New 6-(4-Bromophenyl)-imidazo[2,1-b]thiazole Derivatives: Synthesis and Antimicrobial Activity

Synthesis of Heterocyclic Analogs of α‐aminoadipic Acid and its Esters Based on Imidazo[2,1‐b][1,3]Thiazole

“…To obtain a bromomethylated building block suitable for coupling with amino acid precursors, we investigated the bromination of ethyl 6-methylimidazo[2,1-b] [1,3] thiazole-5-carboxylate (2) prepared from 2-aminothiazole (1) and 2-chloroacetoacetate, as previously described [16]. It is known that the bromination of aromatic hydrocarbon side chains can be easily achieved by their reaction with NBS in the presence of a catalytic amount of a radical initiator [17].…”

“…The synthesis strategy for the target heterocyclic dicarboxylic α-amino acid included the preparation of building blocks possessing the imidazo[2, 1-b] [1,3]thiazole ring system (Schemes 1, 2) followed by coupling with Schöllkopf's chiral auxiliary [10] (Scheme 3) or diethyl (Boc-amino)malonate (Scheme 4). In recent years, Schöllkopf's methodology of stereoselective α-amino acid synthesis was applied as an efficient method for the preparation of enantiomerically pure derivatives of aryl amino acids [11], including phenylalanine [12], constrained cyclic quaternary amino acids [13], and (S)-2-amino-8-oxodecanoic acid [14].…”

“…Herein, we describe the synthesis of imidazo[2,1-b] [1,3]thiazole derivatives, where the ring carbon atoms at C-5 and C-6 are embedded into the main chain of α-aminoadipic acid. (R)-Configurated α-aminoadipic acid is a constituent of cephalosporin C and can be obtained on a large scale by enzymatic cleavage of this antibiotic [6].…”

“…On the other hand, incorporation of the isoxazole nucleus into the (S)-α-aminoadipic acid structure provided the synthetic excitatory amino acid (S)-ACPA (2, Figure 1), which is a potent and selective AMPA receptor agonist [9]. Therefore, the development of methods for the synthesis of α-aminoadipic acid derivatives, possessing imidazo[2, 1-b] [1,3]thiazole moiety, could be of interest in both heterocyclic and medicinal chemistry.…”

“…In recent years, functionalized imidazo [1,2-b] [1,3]thiazole derivatives have been explored as inhibitors of mitochondrial NAHD dehydrogenase [1] and as antitumor [2], antimicrobial [3], cardiodepressant [4], and anticoccidial agents [5].…”